Evaluation of potential toxic and addictive properties of Ethyl acetate

Evaluation of potential toxic and addictive properties of 

Ethyl acetate 

1. Name of substance and physico-chemical properties 

� IUPAC Systematic name: Ethyl acetate 

� Synonyms: AI3-00404; Acetate d'ethyle; Acetate d'ethyle [French]; Acetato de etilo; Acetato de 

etilo [Spanish]; Acetic acid ethyl ester; Acetic ether; Acetidin; Acetoxyethane; Aethylacetat; 

Aethylacetat [German]; CCRIS 6036; Caswell No. 429; EINECS 205-500-4; EPA Pesticide 

Chemical Code 044003; Essigester; Essigester [German]; Ethyl acetate; Ethyl acetate (natural); 

Ethyl acetic ester; Ethyl ester; Ethyl ethanoate; Ethylacetaat; Ethylacetaat[Dutch]; Ethylacetate; 

Ethyle (acetate d'); Ethyle (acetate d') [French]; Ethylester kyseliny octove; Etile (acetato di); Etile 

(acetato di) [Italian]; FEMA No. 2414; HSDB 83; NSC 70930; Octan etylu; Octan etylu [Polish]; 

RCRA waste number U112; UNII-76845O8NMZ; Vinegar naphtha, Cof E n°:191. 

� E Number: No data available to us at this time. 

� Gross Formula: C4-H8-O2 

� Structural Formula: 

� Molecular weight (g/mol): 88.11 

� CAS registration number: 141-78-6 

� Properties: 

Melting point: -8.36E+01°C 

Boiling Point: 77.1°C 

Solubility in water: No data available to us at this time 

pK a: No data available to us at this time.

Flashpoint : 7.2°C (OPEN CUP) 

Flammability limits (vol/vol%): LOWER 2.2%; UPPER 9% 

(Auto)ignition temperature: 800F 

Decomposition temperature: No data available to us at this time 

Stability: Stable under ordinary conditions of use and storage. 

Vapour pressure: 93.2 

log K ow: 0.73 

2. General information 

2.1 Function/category 

2.2 Exposure 

Probable Routes of Human Exposure: NIOSH (NOES Survey 1981-1983) has statistically estimated 

that 375,906 workers (87,691 of these are female) are potentially exposed to ethyl acetate in the 

US(1). Occupational exposure to ethyl acetate may occur through inhalation and dermal contact with 

this compound at workplaces where ethyl acetate is produced or used(SRC). Ethyl acetate was 

identified (relative abundance) in air samples collected where printing pastes (66%) and paints (30%) 

were used, in car repair shops (45%), and in various other industries (57%) in Belgium(2). Mean 

concentrations of ethyl acetate in air during parquet work in Finland were 119 ppm during 

installation with resin adhesives; 319 ppm during puttying; 72 ppm during sanding after puttying; 413 

ppm during undercoat varnishing (nitrocellulose); 64 ppm during urea-formaldehyde varnishing; and 

1 ppm during work with water-based varnishes(3). It was also detected in air during the use of contact 

adhesives at mean concentrations of 14 ppm during repair of a textile carpet (dispersion and contact 

adhesives); 83 ppm during repair of a textile carpet (contact adhesives only); 29 ppm during beading 

of textile carpets (contact adhesives only); and 71 ppm during repair of bathroom floor mats 

(dispersion and contact adhesives)(3). Ethyl acetate was detected in 36% of all air samples, at a mean 

concentration of 11 ppm, collected from Finnish furniture factories from 1975 to 1984(4). Breathing 

zone samples collected during spray painting contained ethyl acetate at a geometric mean 

concentration of 9.51 ppm(5). It was detected in the air of one auto paint shop at a concentration of 

10.5 mg/cu m(6). Ethyl acetate was identified in 12% of 275 products (including thinners, degreasers, 

paints, inks, and dome reagents) used in workplaces in various industries(7). Ethyl acetate was 

identified in the breathing zone of shoe factory workers(8). Ethyl acetate was detected in the ambient 

air of shoe factory in Italy in Nov 1991 at median concentrations of 10 and 7 mg/cu m(9). 

[(1) NIOSH; National Occupational Exposure Survey (NOES) (1983) (2) Veulemans H et al; Am Indust 

Hyg Assoc J 48: 671-7 (1987) (3) Riala REE, Riihimaki HA; Appl Occup Environ Hyg 6: 301-8 (1991) 

(4) Priha E; Ann Occup Hyg 30: 289-94 (1986) (5) Myer HE et al; Am Ind Hyg Assoc J 54: 663-70 

(1993) (6) Medinilla J, Espigares M; Ann Occup Hyg 32: 509-13 (1988) (7) Lehman E et al; pp. 31-41 

in Safety and Health ASP Org Sol Expos Finland April 1985, Riihimaki V, Ulfvarson U, eds NY,NY: 

Alan R Liss Inc (1986) (8) Ahonen I, Schimberg RW; Br J Ind Med 45: 133-6 (1988) (9) Mutti A et al; 

Int Arch Occup Environ Health 65: S171-6 (1993)]

The general population may be exposed to ethyl acetate via inhalation of ambient air, ingestion of 

food and drinking water, and dermal contact with consumer products containing ethyl acetate. (SRC) 

Populations at Special Risk: Employees /with chronic respiratory, skin, liver, or kidney disase may 

be/ at increased risk from ethyl acetate. 

[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health 

Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, 

DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** 

As taken from HSDB powered by Toxnet, 2010 available at http://toxnet.nlm.nih.gov/cgibin/sis/htmlgen?HSDB 

Occurrence in tobacco products: 

In the burned part: Yes 

In tobacco naturally: Yes (Stedman 1968; Lloyd et al., 1976). 

Other sources of exposure : 

Cosmetics : Yes (Cosmetics Bench Ref., 1996) 

Environment: Yes (HSDB, 2002) 

Food: Yes (Fenaroli, 1995) 

Pharmaceuticals: Yes (Martindale, 1993) 

2.3 Combustion products 

This ingredient was investigated in a pyrolysis study. Results are given in Baker and Bishop (2004) J. 

Anal. Appl. Pyrolysis, 71, 2004, pp. 223-311. 

Ingredients 

CAS Number 

Ethyl acetate 

CAS 141-78-6 

CH 2COOCH 2CH 3 

Chemical 

Class 

Mol. 

Wt. 

(M) 

Bp or 

Mp 

( 0 C) 

Ester M=88 

bp77 

Max 

cig 

Appln. 

Level 

(ppm) 

Purity of 

sample 

Pyrolysed 

(%) 

Composition of pyrolysate 

(Compound %) 

Max 

level 

in 

smoke 

(�g) 

550 99 Ethyl acetate 100 275 

When ethyl acetate was pyrolysed (at 300, 600 and 900oC; in helium) the products produced 

included Ethanol; Ethyl acetate ,Benzene ,Acetic acid. (McWhirter 2001). 

2.4 Ingredient(s) from which it originates 

No data available to us at this time.

3. Status in legislation and other official guidance 

FIFRA Requirements: Residues of ethyl acetate are exempted from the requirement of a tolerance 

when used as a solvent or cosolvent in accordance with good agricultural practices as inert (or 

occasionally active) ingredients in pesticide formulations applied to growing crops or to raw 

agricultural commodities after harvest. [40 CFR 180.1001(c) (7/1/97)] **PEER REVIEWED** 

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older 

pesticides to consider their health and environmental effects and make decisions about their future 

use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide 

active ingredients initially registered before November 1, 1984, and determines whether they are 

eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food 

Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior 

to the effective date of FIFRA, as amended in 1988, were divided into three lists based upon their 

potential for human exposure and other factors, with List B containing pesticides of greater concern 

and List D pesticides of less concern. Ethyl acetate is found on List D. Case No: 4005; Pesticide type: 

insecticide, herbicide, antimicrobial; Case Status: OPP is reviewing data from the pesticide's 

producers regarding its human health and/or environmental effects, or OPP is determining the 

pesticide's eligibility for reregistration and developing the Reregistration Eligibility Decision (RED) 

document.; Active ingredient (AI): Ethyl acetate; AI Status: The active ingredient is no longer 

contained in any registered pesticide products ... "cancelled." 

[USEPA/OPP; Status of Pesticides in Registration, Reregistration and Special Review p.292 (Spring, 

1998) EPA 738-R-98-002] **QC REVIEWED** 

TSCA Requirements: A testing consent order is in effect for ethyl acetate for health effects testing. FR 

citation: 1/23/95. [40 CFR 799.5000 (7/1/97)] **PEER REVIEWED** 

CERCLA Reportable Quantities: Persons in charge of vessels or facilities are required to notify the 

National Response Center (NRC) immediately, when there is a release of this designated hazardous 

substance, in an amount equal to or greater than its reportable quantity of 5000 lb or 2270 kg. The 

toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426- 

2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. 

D.3.b). [40 CFR 302.4 (7/1/97)] **PEER REVIEWED** 

RCRA Requirements: U112; As stipulated in 40 CFR 261.33, when ethyl acetate, as a commercial 

chemical product or manufacturing chemical intermediate or an off-specification commercial 

chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed 

according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is 

any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water 

or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial 

exclusion from hazardous waste regulations (40 CFR 261.5). [40 CFR 261.33 (7/1/97)] **PEER 

REVIEWED** 

F003; When ethyl acetate is a spent solvent, it is classified as a hazardous waste from a nonspecific 

source (F003), as stated in 40 CFR 261.31, and must be managed according to State and/or Federal 

hazardous waste regulations. [40 CFR 261.31 (7/1/97)] **PEER REVIEWED**

Atmospheric Standards: This action promulgates standards of performance for equipment leaks of 

Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry 

(SOCMI). The intended effect of these standards is to require all newly constructed, modified, and 

reconstructed SOCMI process units to use the best demonstrated system of continuous emission 

reduction for equipment leaks of VOC, considering costs, non air quality health and environmental 

impact and energy requirements. Ethyl acetate is produced, as an intermediate or final product, by 

process units covered under this subpart. [40 CFR 60.489 (7/1/97)] **PEER REVIEWED** 

FDA Requirements: Certification of this color additive when used as a diluent (in inks for marking 

fruit & vegetables) is not necessary for the protection of the public health and therefore batches 

thereof are exempt from the requirements of section 706(c) of the Federal Food, Drug, and Cosmetic 

Act. /Restrictions incl no residue./ [21 CFR 73.1 (4/1/97)] **PEER REVIEWED** 

Synthetic flavoring substances and adjuvants /for human consumption/ that are generally recognized 

as safe for their intended use, within the meaning of section 409 of the Act. Ethyl acetate is included 

on this list. [21 CFR 182.60 (4/1/97)] **PEER REVIEWED** 

Synthetic flavoring substances and adjuvants /for animal drugs, feeds, and related products/ that are 

generally recognized as safe for their intended use, within the meaning of section 409 of the Act. 

Ethyl acetate is included on this list. [21 CFR 582.60 (4/1/97)] **PEER REVIEWED** 

Allowable Tolerances: Residues of ethyl acetate are exempted from the requirement of a tolerance 

when used as a solvent or cosolvent in accordance with good agricultural practices as inert (or 

occasionally active) ingredients in pesticide formulations applied to growing crops or to raw 

agricultural commodities after harvest. [40 CFR 180.1001(c) (7/1/97)] **PEER REVIEWED** 

OSHA Standards: Permissible Exposure Limit: Table Z-1 8-hr Time Weighted Avg: 400 ppm (1400 

mg/cu m). [29 CFR 1910.1000 (7/1/98)] **QC REVIEWED** 

Threshold Limit Values: 8 hr Time Weighted Avg (TWA): 400 ppm. 

[American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values 

for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH, 2008, 

p. 29] **QC REVIEWED** 

Excursion Limit Recommendation: Excursions in worker exposure levels may exceed 3 times the TLV- 

TWA for no more than a total of 30 minutes during a work day, and under no circumstances should 

they exceed 5 times the TLV-TWA, provided that the TLV-TWA is not exceeded. 

[American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values 

for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH, 2008, 

p. 5] **QC REVIEWED** 

NIOSH Recommendations: Recommended Exposure Limit: 10 Hr Time-Weighted Avg: 400 ppm 

(1400 mg/cu m). [NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication 

No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 130] **QC REVIEWED** 

Immediately Dangerous to Life or Health: 2000 ppm (Based on 10% of the lower explosive limit for 

safety considerations even though the relevant toxicological data indicated that irreversible health

effects or impairment of escape existed only at higher concentrations.) [NIOSH. NIOSH Pocket Guide 

to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government 

Printing Office, 1997., p. 130] **QC REVIEWED** 

Other Standards Regulations and Guidelines: USSR (1973): 55 ppm; Czechoslovakia (1969): 110 

ppm; Sweden (1974): 300 ppm; Italy (1975): 220 ppm. [American Conference of Governmental 

Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 

5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986.] **PEER 

REVIEWED** 


Summary of Evaluations Performed by the Joint FAO/WHO Expert Committee on Food Additives 

ETHYL ACETATE 

COE No.: 191 

FEMA No.: 2414 

JECFA No.: 27 

Chemical names: ETHYL ACETATE 

Synonyms: ACETIC ACID ETHYL ESTER; ETHYL ETHANOATE 

Functional class: FLAVOURING AGENT; CARRIER SOLVENT 

Latest evaluation: 1996 

ADI: 0-25 mg/kg bw (1967) 

Comments: No safety concern at current levels of intake when used as a flavouring agent. The 

1967 ADI of 0-25 mg/kg bw was maintained at the forty-sixth meeting (1997). 

Report: TRS 868-JECFA 46/21 

Specifications: COMPENDIUM ADDENDUM 4/FNP 52 Add.4/49 (SOLVENT); 177 (FLAVOUR) 

Tox monograph: See TRS 868-JECFA 46/64 

Previous status: 1967, NMRS 44/TRS 383-JECFA 11/12, FAS 69.31/NMRS 44B-JECFA 11/16 

(COMPENDIUM/581), FAS 68.33/NMRS 44A-JECFA 11/23. 0-25. FU. N 

As taken from JECFA evaluation of Ethyl Acetate available at 

http://www.inchem.org/documents/jecfa/jeceval/jec_711.htm 

4. Metabolism/Pharmacokinetics 

4.1 Metabolism/metabolites 

... ETHYL ACETATE ... METABOLISM PRODUCES CORRESPONDING ETHYL ALCOHOL & IS 

PARTLY EXCRETED IN EXHALED AIR & URINE & PARTLY METABOLIZED.

[Snyder, R. (ed.). Ethel Browning's Toxicity and Metabolism of Industrial Solvents. Second Edition. 

Volume 3 Alcohols and Esters. New York, NY: Elsevier, 1992., p. 237] **PEER REVIEWED** 

AT HIGHER LEVELS, THE RATE OF HYDROLYSIS OF ETHYL ACETATE /IN RATS/ APPEARED TO 

EXCEED ETHANOL OXIDATION, LEADING TO ITS (ETHANOL'S) ACCUMULATION IN THE 

VASCULAR SYSTEM. ALSO, WHEN IT (ETHYL ACETATE) WAS INJECTED IP AT 1.6 G/KG, 

HYDROLYSIS TO ACETIC ACID AND ETHANOL OCCURRED RAPIDLY. 

[Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 

2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 2983-4] 

**PEER REVIEWED** 


Type: Metabolism 

Remark: 

Source: 

Hydrolysis rate of ethyl acetate in rat ethmoturbinate S9 

homogenate: 30 nmol/mg S9 protein/min. 

BP Chemicals Ltd. London 

(173) 

Type: Metabolism 

Remark: 

In vitro incubation of 360 mg ethyl acetate/l with pig 

jejunum homogenate for 2 h caused 100 % hydrolysis; 

incubation of 81 mg ethyl acetate/l with pancreatin 

did not cause any measurable hydrolysis; 37 degree C; 

pH 7.5. 

Source: BP Chemicals Ltd. London(174) 

Type: Metabolism

Remark: 

In vitro incubation of 0.2 g ethyl acetate/100 ml blood for 

5 h at 37 degree C revealed a half–time of 65 – 70 min in 

rat blood. 

In vivo studies: 

1.6 ml ethyl acetate/kg bw was injected i.p. into 

anaesthetized rats and blood samples were withdrawn 

periodically: hydrolysis to ethanol was very rapid with a 

half–time estimated at 5 – 10 min. 

Continuous inhalation of ethyl acetate by anaesthetized 

rats via an endotracheal tube led to an accumulation of 

ethanol in blood when the ethyl acetate vapour concentration 

was increased above 7320 mg/m3; no appreciable ethyl acetate 

concentration was found in blood (< 10 mg/100 ml). 

Ethyl acetate and ethanol were determined gaschromato– 

graphically. 

Source: BP Chemicals Ltd. London 

Test substance: 

reagent grade ethyl acetate; i.p. injection study: 25 % 

(v/v) ethyl acetate in corn oil 

(175) 

Type: Metabolism

Remark: 

Ethyl acetate deposition was measured in the surgically 

isolated upper resipratory tracts (URT) of rats and 

hamsters; degree of metabolism was estimated by mathematical 

modelling and by comparison of deposition efficiencies in 

control animals and carboxylesterase–inhibited animals: 

ethyl acetate deposited was 10 – 35 % of inspired vapour in 

rats and 36 – 72 % of inspired vapour in hamsters; 

significant amounts of ethyl acetate were metabolized in the 

URT of both species: rat 40 – 65 %, hamster 63 – 90 % of 

deposited substance. 


As taken from IUCLID Dataset (2000), Ethyl acetate (141-78-6). 

4.2 Absorption, distribution and excretion 

Ethyl acetate may cause adverse health effects following exposure via inhalation, ingestion or dermal 

contact. The primary route of absorption responsible for the toxicity of ethyl acetate is inhalation. 

[Ryan, R.P., C.E. Terry (eds.). Toxicology Desk Reference 4th ed. Volumes 1-3. Taylor & Francis, 

Washington, D.C. 1997., p. 1253] **PEER REVIEWED** 

As taken from HSDB powered by Toxnet, 2010 available at http://toxnet.nlm.nih.gov/cgibin/sis/htmlgen?HSDB

Remark: 

16 male volunteers were exposed to 1449 mg ethyl acetate/m3 air (402 ppm) for 4 h 

(dynamic exposure with an air exchange 

of 7.5 times per hour): 30 min after the beginning the alveolar concentration 

reached 16 % (= 235 mg/m3) of the exposure concentration and 

dropped to 2.0 % (= 29 mg/m3) within 30 – 60 min after 

cessation of exposure; concentration of ethanol (metabolite) in the alveolar air 

during exposure: 4.2 ppm (8 mg/m3); cumulative excretion of ethyl acetate in urine 

reached 1.75 mg within 2 h after exposure cessation and no further ethyl acetate was 

excreted in the urine. 

Source: BP Chemicals Ltd. London (184) 

Type: other: Transdermal flux 

Remark: 

Transdermal steady state flux of ethyl acetate through 4 types of skin: human cadaver 

skin (A): 0.5 mg/cm2/h, lag time: 24 h human cadaver skin (B): 0.5 mg/cm2/h, lag 

time: 20 h rat skin (A): 12 mg/cm2/h, lag time: 8 h rat skin (B): 10 mg/cm2/h, lag 

time: 8 h hairless mouse skin (B): 18 mg/cm2/h, lag time: 6 h hairless guinea pig skin 

(B): 7 mg/cm2/h, lag time 8 h; Franz diffusion cells; receptor phase (isotonic saline): 

37 degree C; donor phase: 32 degree C. 

Source: BP Chemicals Ltd. London


A. levonorgestrel was diluted in neat ethyl acetate; B. levonorgestrel was diluted in a 

70 % solution of ethyl acetate in ethanol (179) 

Type: other: Accumulation in Rat 

Remark: 

8.6 % of the applied dose were found to be stored in rats5 d after a single 

administration of ethyl acetate by gavage; dose was equivalent to 1 mg/kg in diet; no 

further data available. 



4.3 Interactions 

ETHYL ACETATE IN COMBINATION WITH TOLUENE APPEARED TO PRODUCE A MIXTURE OF 

LOWER TOXICITY THAN THAT OF EITHER COMPOUND ALONE. MIXING OF ETHYL ACETATE 

WITH PROPYLENE OXIDE, PROPYLENE GLYCOL, OR FORMALIN APPEARS TO DECR ITS LD50 

VALUE, BUT ITS TOXICITY INCREASES IN COMBINATION WITH MORPHOLINE, ETHYLENE 

GLYCOL, OR ETHYL ALCOHOL. 


2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 2984] **PEER 

REVIEWED** As taken from HSDB: 83. Last Revision Date: 2005/06/24 powered by Toxnet at 

http://toxnet.nlm.nih.gov/ 

5. Toxicity 

5.1 Single dose toxicity 

Organism Test 

Type 

Route Reported Dose 

(Normalized 

Dose) 

cat LCLo inhalation 61gm/m3 

(61000mg/m3) 

Effect Source 

"Handbook of 

Toxicology," 4 vols., 

Philadelphia, W.B. 

Saunders Co., 1956- 

59Vol. 1, Pg. 336, 

1955.

Organism Test 

Type 


(Normalized 

Dose) 

cat LD50 subcutaneous 3gm/kg 

(3000mg/kg) 

guinea pig LD50 oral 5500mg/kg 

(5500mg/kg) 

guinea pig LD50 subcutaneous 3gm/kg 

(3000mg/kg) 

human TCLo inhalation 400ppm 

(400ppm) 

mouse LC50 inhalation 45gm/m3/2H 

(45000mg/m3) 

Effect Source 

BEHAVIORAL: 

SOMNOLENCE (GENERAL 

DEPRESSED ACTIVITY) 

GASTROINTESTINAL: 

NAUSEA OR VOMITING 

BLOOD: OTHER 

CHANGES 

BEHAVIORAL: 



BEHAVIORAL: CHANGES 

IN MOTOR ACTIVITY 

(SPECIFIC ASSAY) 

BEHAVIORAL: COMA 

BEHAVIORAL: 



SENSE ORGANS AND 

SPECIAL SENSES: OTHER 

CHANGES: OLFACTION 

SENSE ORGANS AND 

SPECIAL SENSES: 

CONJUNCTIVE 

IRRITATION: EYE 

LUNGS, THORAX, OR 

RESPIRATION: OTHER 

CHANGES 

Archiv fuer 

Gewerbepathologie 

und Gewerbehygiene. 

Vol. 5, Pg. 1, 1933. 

Gigiena i Sanitariya. 

For English translation, 

see HYSAAV. Vol. 

48(4), Pg. 66, 1983. 

Archiv fuer 

Gewerbepathologie 

und Gewerbehygiene. 

Vol. 5, Pg. 1, 1933. 

Journal of Industrial 

Hygiene and 

Toxicology. Vol. 25, 

Pg. 282, 1943. 

"Toxicometric 

Parameters of 

Industrial Toxic 

Chemicals Under 

Single Exposure," 

Izmerov, N.F., et al., 

Moscow, Centre of 

International Projects, 

GKNT, 1982Vol. -, Pg. 

65, 1982.

Organism Test 

Type 


(Normalized 

Dose) 

mouse LD50 intraperitoneal 709mg/kg 

(709mg/kg) 

mouse LD50 oral 4100mg/kg 

(4100mg/kg) 

rabbit LD50 oral 4935mg/kg 

(4935mg/kg) 

rabbit LD50 skin > 20mL/kg 

(20mL/kg) 

rat LC50 inhalation 200gm/m3 

(200000mg/m3) 

rat LD50 oral 5620mg/kg 

(5620mg/kg) 

rat LDLo subcutaneous 5gm/kg 

(5000mg/kg) 

Effect Source 

BEHAVIORAL: 



BEHAVIORAL: CHANGES 

IN MOTOR ACTIVITY 

(SPECIFIC ASSAY) 

BEHAVIORAL: COMA 

BEHAVIORAL: 



GASTROINTESTINAL: 

CHANGES IN STRUCTURE 

OR FUNCTION OF 

SALIVARY GLANDS 

LUNGS, THORAX, OR 

RESPIRATION: ACUTE 

PULMONARY EDEMA 

Shell Chemical 

Company. 

Unpublished Report. 

Vol. -, Pg. 5, 1961. 

Gigiena i Sanitariya. 

For English translation, 

see HYSAAV. Vol. 

48(4), Pg. 66, 1983. 

Industrial Medicine 

and Surgery. Vol. 41, 

Pg. 31, 1972. 

Union Carbide Data 

Sheet. Vol. 10/4/1968, 

Science Reports of the 

Research Institutes, 

Tohoku University, 

Series C: Medicine. 

Vol. 36(1-4), Pg. 10, 

1989. 

Yakkyoku. Pharmacy. 

Vol. 32, Pg. 1241, 

1981. 

Bolletino della Societe 

Italiana di Biologia 

Sperimentale. Vol. 18, 

Pg. 45, 1943. 

As taken from ChemIDplus powered by Toxnet, 2010 available at http://toxnet.nlm.nih.gov/cgibin/sis/htmlgen?CHEM 

Non-Human Toxicity Values:

LD50 Rat oral 5.6 g/kg /From table/ 



REVIEWED** 

LD50 Rabbit oral 4.94 g/kg /From table/ 



REVIEWED** 

LD50 Mouse oral 0.44 g/kg /From table/ 



REVIEWED** 

LD50 Guinea pig sc 3.0 g/kg /From table/ 



REVIEWED** 

LD50 Cat sc 3.0 g/kg /From table/ 



REVIEWED** 

LD50 Rat oral 11.3 ml/kg 

[The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983., p. 545] **PEER 

REVIEWED** 

LD50 Rabbit oral 4.9 g/kg 

[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. 

Baltimore: Williams and Wilkins, 1984., p. II-201] **PEER REVIEWED** 

LD50 Mouse inhalation 1500 ppm/4hr 



LD50 Rabbit inhalation 2500 ppm/4hr 



LD50 Rat inhalation 4000 ppm/4hr 



LC50 Rat inhalation 16,000 ppm/6hr

[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold 

Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 

1991., p. 569] **PEER REVIEWED** 

Acute Inhalation: 

... ANIMALS COULD WITHSTAND CONCN OF ETHYL ACETATE OF 2000 PPM FOR 65, 4 HR 

EXPOSURES WITHOUT APPARENT ILL EFFECTS AS MEASURED BY LACK OF CHANGE IN BODY 

WT & IN RED & WHITE BLOOD COUNTS. 

[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold 

Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 

1991., p. 569] **PEER REVIEWED** 


Rat Oral LD 50 5.6-10.2 g/kg bw (BIBRA, 1992) 

Mouse Oral LD 50 4.1 g/kg bw (BIBRA, 1992) 

Rat 8-hr LC 50 5.86 mg/l (BIBRA, 1992) 

Mouse 3-hr LC 50 44 mg/l (BIBRA, 1992) 

A man died from inhaling the vapour from a lacquer contaning 80 % ethyl acetate. Examination at 

autopsy revealed accumulation of blood in the upper respiratory tract, the spleen and the kidneys, 

minute haemorrhages of the pleura and the outer wall of the heart, and inflammation and bleeding of 

the stomach (BIBRA, 1992). 

“Ethyl acetate is low in toxicity. It is a mild mucous membrane irritant, but is not caustic. In high 

concentrations it may be a CNS depressant. Animal studies have demonstrated pulmonary edema, 

decreased cardiac contractility, seizures and hepatic damage, but these have NOT been reported in 

humans.” 

“Immediately Dangerous to Life or Health: 2000 ppm (Based on 10% of the lower explosive limit for 

safety considerations even though the relevant toxicological data indicated that irreversible health 

effects or impairment of escape existed only at higher concentrations.)“ 


Species Route Dose data Toxic effects 

Human Inhalation TCLo: 400 ppm D07, D25, J30

Rat Oral LC 50: 200 g/m 3 F07, J15, K01 

Rat Subcutaneous LDLo: 5 g/kg - 

Mouse Oral LD 50: 4.1 g/kg F07, F17, F24 

Mouse Inhalation LC 50: 45 g/m 3 /2h - 

Mouse Intraperitoneal LD 50: 0.709 g/kg - 

Cat Inhalation LCLo: 61 g/m 3 - 

Cat Subcutaneous LD 50: 3 g/kg F07, K13, P30 

Rabbit Oral LD 50: 4.935 g/kg - 

Rabbit Skin LD 50: > 20 mL/kg - 

Guinea pig Oral LD 50: 5.5 g/kg F07, F17, F24 

Guinea pig Subcutaneous LD 50: 3 g/kg F07 

Mouse Inhalation TCLo: 200 ppm/6M J25 

As taken from RTECS AH5425000 available at http://www.drugfuture.com/toxic/q4-q13.html 

Species Route Dose data 

Rat Oral LD 50: 6.1 g/kg bw 

Rabbit Oral LD 50: 7.65 g/kg bw 

Rat Inhalation LC 50: 0.2 g/L 

Rat Inhalation LC: 0.0577 g/L 

Mouse Inhalation LC 50: 0.0335 g/L 

Mouse Inhalation LCLo: 0.031 g/L 

Rat Intraperitoneal LD 50: 2.11 g/kg bw 

Mouse Intraperitoneal LD 50: 1 g/kg bw 

As taken from IUCLID Dataset (2000), Ethyl acetate (141-78-6).

“Intravenous injection of 9.5 mL of a 5% solution of ethyl acetate/animal (v/v: 428 mg/rabbit) caused 

no changes of blood pressure or respiration.” 

“Heart rate and systemic arterial blood pressure were reduced progressively whilst pulmonary arterial 

pressure increased gradually during continuous infusion, myocardial contractile force decreased 

progressively as the blood concentrations reached > 0.3 mg/mL; exposure period: 40-150min 

(probably 60min); 6 anaesthetized, open chest dogs.” 

“Mice were exposed to ethyl acetate by cumulative inhalation of increasing concentration fot 30 min 

(each concentration): EC 50 for schedule-controlled behaviour (response to appropriate stimulti 

rewarded with milk presentation) = 2174 mg/m 3 (standard deviation = 447); abolished responding in 

all mice; all mice recovered completely 30min; mice were weight-reduced to 80% of the free feeding 

weight.” 

As tken from IUCLID Dataset (2000), Ethyl acetate (141-78-6). 

Humans 

Acute exposure 

The ACGIH TLV-TWA of 400 ppm [1440 mg/m 3 

] was established to minimize the potential risk for 

irritation of the eyes, nose, and upper respiratory tract [see below] (ACGIH, 2002). 

Exposure of 10 individuals to a vapour containing 400 ppm [1440 mg/m 3 

] for 3-5 minutes resulted in 

irritation to the eyes, nose, and throat. No irritation was reported at 200 ppm [720 mg/m 3 

], but this 

concentration was regarded by some as having intense odour. Most of the volunteers found 100 ppm 

[360 mg/m 3 

] tolerable for 8 hr exposure (Nelson et al. 1943). 

In an early report, a man died from inhaling the vapour (in an enclosed tank) from a lacquer 

containing 80% ethyl acetate [the remaining 20% of the lacquer was not identified]. Accumulation of 

blood in the upper respiratory tract, spleen, and kidneys; minute haemorrhages of the membranes 

covering the lungs and outer wall of the heart; and inflammation and bleeding of the stomach were 

observed (Althoff, 1931). 

Laboratory animals 

Acute exposure 

Rat. 8-hr LC 50 : 5.86 mg/l (Patty, 1963). 

[exposure time unknown] LC 50 : 200 mg/l (Kawasaki et al. 1975). 

All six rats survived a 4-hr exposure to 8000 ppm [28.8 mg/l], but all six died at 16,000 ppm [57.6 

mg/l] for 4 hr (Smyth et al. 1962). Deaths occurred within 19-70 minutes following exposure to air 

containing 2.5-10% [92-366 mg/l] ethyl acetate (Kojima et al. 1977). 

Mouse. 3-hr LC 50 : 44 mg/l (Spealman et al. 1945). 

2-hr LC 50 : 45 mg/l (Izmerov et al. 1977).

In studies involving exposures lasting for 5-10 minutes, the concentration causing a 50% decrease in 

respiratory rate (RC 50 ) [indicative of local irritation] was determined to be 580-614 ppm [2.1-2.2 mg/l] 

(de Ceaurriz et al. 1981; Kane et al. 1980). 

5.2 Chronic toxicity 

CHRONIC, REPEATED INHALATION BY MICE 6 HR/DAY FOR 7 DAYS OF 4200-4400 PPM /& BY 

GUINEA PIGS OF 2000 PPM/ WAS FOUND ... TO CAUSE NO DEFINITE ... /SRP: CNS 

DEPRESSANT/ SYMPTOMS, BUT ... NOTED INCR IN ERYTHROCYTES WITH NO 

CORRESPONDING INCR IN HEMOGLOBIN, & SOME INCR IN POLYMORPHS. ... THERE WAS 

LOSS OF APPETITE ... NO CHANGE IN ... URINE ... . 




Male and female rats were exposed to 0 ppm (n=36), 350 ppm (n=24), 750 ppm (n=24) or 1500 

ppm (n=36), 6 hr/day, 5 days/week, for 13 weeks. Reductions in growth and feed efficiency were 

observed in males at 350 ppm and above. Reduced body weight and feed consumption were seen at 

750 and 1500 ppm. Behavioural effects were reported at the highest dose (Christoph et al. 2003). 

According to the English abstract of a Soviet study, continuous exposure of rats and mice to 0.01- 

0.043 mg/l for 90 days caused functional disturbances and structural changes in undisclosed body 

organs, but no such effects were reported at 0.002 mg/l (Solomin et al. 1975). A second English 

abstract [possibly of the same study] reported that rats inhaling 0.01-0.05 mg/l continuously for 90 

days developed severe microscopic changes in the thyroid. A second group of similarly exposed rats 

(that were restricted in movement) exhibited changes in the microscopic structure of the brain, and 

kidney damage (Tikhonova et al. 1975). The reliability of these studies is uncertain. 

A brief report of an unpublished study notes that olfactory degeneration was observed in male and 

female rats exposed for 90 days to atmospheres containing 350 and 1500 ppm (Anon, 1996). 

In early studies, blood chemistry changes were observed in mice and cats inhaling 15-16 mg/l, 6-8 

hr/day, for 1 wk (Flury & Wirth, 1933) and in rabbits following exposure at 16 mg/l, 6 hr/day for 40 

days (Blina, 1933a). According to a brief summary, repeated exposure [duration unspecified] of 

rabbits at 4450 ppm evidently resulted in blood chemistry changes and damage to the liver (cited in 

ACGIH, 2002). 

No overt effects developed in three guinea pigs following 65 4-hr exposures over 10 weeks (daily for 

two weeks, then 6 days/week for the remaining period) at 2000 ppm [7.2 mg/l] (Smyth & Smyth, 

1928). 

Human Case: 

No adverse symptoms were reported in an undisclosed number of workers exposed for several 

months to atmospheric concentrations of 1.3-5.4 mg/l [1300-5400 mg/m 3 

] (Patty, 1963).

Repeated Dose Toxicity 

Species: rat 

Route of admin.: inhalation 

Exposure period: 90 d 

Frequency of 

treatment: 

continuous 

Post. obs. Period: no data 

Doses: 0, 0.002, 0.01 and 0.043 mg/l air 

Control Group: other: yes, concurrent unspecified 

NOAEL: = .002 mg/l 

Method: other: Repeated Inhalation Toxicity 

Remark: 0.010 and 0.043 mg/l: significantly increased number of leukocytes after 30 d; 

increased motoric chronaxy after 15 and 30 d; decreased cholinesterase activity 

during the whole exposure period (minimum at day 15); significantly reduced body 

weight after 90 d; pathological changes of the cerebral cortex (swelling, 

hyperchromemia), liver (decreased glycogen and lipid level), thyroid gland (follicle 

degeneration, infiltration) and adrenal gland (hypertrophy of the cortex). 


Species: rat 

Sex: female 

Strain: Wistar 




treatment: 

8 h/d 

Post. obs. period: 1 d 

Doses: 1.1 mg/l air (300 ppm)

Method: other: Repeated Inhalation Effects 

other TS: >= 99 % pure 

Remark: No changes in the activity of alkaline phosphatases originating from leukocytes or 

serum; enzyme assays were conducted on day 8; dynamic exposure; Alkaline 

PhosphaK–test (trade name); 7 rats. 


Species: rat 

Sex: male/female 

Strain: no data 

Route of admin.: gavage 



treatment: 

daily 

Post. obs. period: none 

Doses: 0, 300, 900 and 3600 mg/kg bw d 

Control Group: other: yes, concurrent: animals were gavaged 

NOAEL: = 900 mg/kg bw 

LOAEL: = 3600 mg/kg bw 

Method: other: Rat Oral Subchronic Study, US EPA 

Remark: 3600 mg/kg bw d: Male rats showed significantly depressed body and organ weights, 

and depressed food consumption; female rats showed nonsignificant depression of 

above parameters compared with controls; 30 animals/sex/dose and control. 

Source: BP Chemicals Ltd. London(146)

Species: rat 

Sex: male 

Strain: no data 

Route of admin.: i.p. 

Exposure period: one to eight days 


treatment: 

daily 

Post. obs. period: no data specified 

Doses: 900 mg/kg bw d 

Control Group: other: yes, concurrent unspecified 

Method: other: Repeated i.p. Toxicity 

Test substance: other TS: presumably neat 

Remark: After 8 d of exposure liver pyruvate, blood and liver lactate levels were increased, 

blood pyruvate increased with increasing time (daily measurement), liver glycogen 

was decreased; liver enzyme activities: glucose–6–phosphatase activity was 

decreased; lactate dehydrogenase activity was increased; ethyl acetate had no effect 

on ATPase, 5’–nucleotidase, acid phosphatase or succinate dehydrogenase activity; 6 

– 12 animals per enzyme test or liver and blood level determination. 


Species: mouse 



Frequency 

oftreatment: 

continuous 

Post. obs. period: no data

Doses: 0, .002, .010, .043 mg/l air 

Control Group: no data specified 

NOAEL: = .002 mg/l 


Remark: Functional disturbances in the state of the animals (e.g. increased motoric chronaxy 

after 15 and 30 d of exposure) and morphological changes in their viscera were seen 

at 0.010 and 0.043 mg/l; 7 mice/dose group; no further data available. 


Species: rabbit 


Exposure period: 7 w 


treatment: 

Post. obs. period: 3 w 

8/d, 5 d/w 

Doses: ca. 5 – 62 mg/l air 


LOAEL: 5 – 10 mg/l 


Test substance: other TS: 99.6 % pure 

Remark: 35 – 62 mg/l: slight loss in body weight; post exposure observation did not reveal any 

signs of pathological changes (behaviour, appetite, blood count, urinalysis), not even 

of the eyes; at the beginning of the exposure intensive swelling and injection of lids 

and conjunctiva occurred but disappeared during the exposure period; it could be 

shown that the conjunctiva got accustomed to the vapour: exposing an untreated 

rabbit to ethyl acetate in the 4th week of the study the known strong irritation was 

achieved, whereas the 4–week–treated rabbits already showed a moderate 

reddening; no corneal changes throughout the study. 






treatment: 

60 min/d 

Post. obs. period: no data specified 

Doses: 16 mg/l 



Year: 1933 

Test substance: no data 

Remark: Result secondary anaemia with leukocytosis, hyperaemia, cloudy swelling and fatty 

degeneration of various organs and variable intensity. 


Species: cat 





treatment: 

6 h/d 

Post. obs. period: 6 d 

Doses: 15 – 16 mg/l 

Control Group: no data specified


Year: 1933 

Remark: during exposure: strong salivation, lacrimation, respiratory rate declined to 20 min–1; 

at the end of the exposure period: decreased appetite, body weight loss, increased 

number of erythrocytes, no changes in hemoglobin or number of leukocytes (relative 

increase in the number of neutrophils and relative decrease in the number of 

lymphocytes), no pathological changes in the urine 


Species: guinea pig 


Exposure period: 10.5 w (65 exposures) 


treatment: 

Post. obs. period: none 

Doses: 7.3 mg/l (2000 ppm) 

Control Group: yes, concurrent vehicle 

during the first two weeks: daily, thereafter: 4 h/d, 6 d/w 


Remark: Whole–body vapour exposure; animals remained in good condition and showed no 

evidence of harm; animals were weighed weekly, blood counts and urinalysis were 

carried out every 2 weeks; 3 animals. 



5.3 Reproduction toxicity 

No effects in sperm count were detected in a study of 11 printing factory workers occupationally 

exposed to an atmosphere reportedly containing ethyl acetate at 150 ppm (BIBRA, 1992).

“No reproductive studies were found for ethyl acetate in humans. Inhalation of lacquer thinner, 

which contains ethyl acetate, in male rats produced lower testicular and prostate weights. Ethyl 

acetate alone produced similar effects and also reduced the number of spermatozoa.” 

“WHEN ETHYL ACETATE WAS INJECTED INTO THE YOLK SAC OF FRESH FERTILE CHICKEN EGGS 

BEFORE INCUBATION IN A DOSE OF 9, 22.5, 45, OR 90 MG/EGG, THE HATCHABILITIES WERE 

85, 50, 35, AND 15%, RESPECTIVELY.” 


Developmental Toxicity/Teratogenicity 

Species: hen 


Strain: Leghorn 

Route of admin.: other: injected into egg. 

Exposure period: Incubation period or incubation period–4 days. 


treatment: 

Single injection. 

Doses: Up to 25 mg/egg. 


Method: other: groups of 100 chick eggs treated at each of 5 dose levels. Eggs were candled 

daily. Non–viable embryos and hatched chicks were examined grossly for 

abnormalities and signs of toxicity. 

Test substance: other TS: ethyl acetate in absolute alcohol. 

Remark: Ethyl acetate showed no teratogenic effects. 


Species: hen


Route of admin.: other: yolk sac of fertile eggs 

Duration of test: until hatch 

Doses: 9 – 90 mg/egg 


Method: other: % hatch determined after injection of ethyl acetate into the yolk sac of fresh 

fertile chicken eggs at 9, 22.5, 45 or 90 mg/egg. 

Year: 1963 

GLP: no data 

Test substance: other TS 

Remark: Hatchability was 95% in the control group (boiled water) and decreased dosage– 

relatedly through 85%, 50% and 35% to 15% at the highest dosage. 


Human Study: 

Remark: 

No effects on sperm count were detected in a study of eleven printing factory workers 

occupationally exposed (for an undisclosed time) to an atmosphere reportedly 

containing ethyl acetate at 150 ppm (549 mg/m3) and other organic solvents. 



5.4 Mutagenicity 

Mutagenicity Studies: 

Test System: AMES SALMONELLA TYPHIMURIUM

Strain Indicator: TA100 

Metabolic Activation: NONE 

Method: PREINCUBATION 

Dose: 100-10000 UG/PLATE (TEST MATERIAL SOLVENT: DMSO) 

Results: NEGATIVE 

Reference: [ZEIGER,E, ANDERSON,B, HAWORTH,S, LAWLOR,T AND MORTELMANS,K; 

SALMONELLA MUTAGENICITY TESTS. V. RESULTS FROM THE TESTING OF 311 

CHEMICALS; ENVIRON. MOL. MUTAGEN. 19(SUPPL.21):2-141, 1992] 

Test System: AMES SALMONELLA TYPHIMURIUM 


Metabolic Activation: HAMSTER, LIVER, S-9, AROCLOR 1254 (10 OR 30%) 









Metabolic Activation: RAT, LIVER, S-9, AROCLOR 1254 (10 OR 30%) 



Results: NEGATIVE























Strain Indicator: TA1535























Reference: [ZEIGER,E, ANDERSON,B, HAWORTH,S, LAWLOR,T AND MORTELMANS,K;























Metabolic Activation: HAMSTER, LIVER, S-9, AROCLOR 1254 (10 OR 30%)
























CHEMICALS; ENVIRON. MOL. MUTAGEN. 19(SUPPL.21):2-141, 1992]



Metabolic Activation: HAMSTER, LIVER, S-9, AROCLOR 1254 (30%) 









Metabolic Activation: RAT, LIVER, S-9, AROCLOR 1254 (30%) 







Test System: CHO-LB CELLS 

End Point: IN VITRO CHROMOSOMAL ABERRATIONS 


Dose: 500; 1510; 5010 UG/ML (TEST MATERIAL SOLVENT: DMSO)

Dose Regimen: 8 HR TREATMENT, 2.5 HR RECOVERY WITH COLCEMID ADDED 


Reference: [LOVEDAY,KS ANDERSON,BE RESNICK,MA ZEIGER,E; CHROMOSOME 

ABERRATION AND SISTER CHROMATID EXCHANGE TESTS IN CHINESE 

HAMSTER OVARY CELLS IN VITRO, V: RESULTS WITH 46 CHEMICALS; 

ENVIRON. MOL. MUTAGEN. 16(9):272-303, 1990] 



Metabolic Activation: RAT, LIVER, S-9, AROCLOR 1254 

Dose: 500; 1510; 5010 UG/ML (TEST MATERIAL SOLVENT: DMSO) 

Dose Regimen: 2 HR TREATMENT, 18 HR RECOVERY WITH COLCEMID ADDED 2 HR BEFORE 

HARVEST 



ABERRATION AND SISTER CHROMATID EXCHANGE TESTS IN CHINESE 





Metabolic Activation: RAT, LIVER, S-9, AROCLOR 1254 

Dose: 3010; 4020; 5020 UG/ML (TEST MATERIAL SOLVENT: DMSO) 

Dose Regimen: 2 HR TREATMENT, 10 HR RECOVERY WITH COLCEMID ADDED 2 HR BEFORE 

HARVEST 



ABERRATION AND SISTER CHROMATID EXCHANGE TESTS IN CHINESE







Dose: 0.0763-5000 UG/PLATE (TEST MATERIAL SOLVENT: WATER) 


Reference: [JAPAN CHEMICAL INDUSTRY ECOLOGY- TOXICOLOGY AND INFORMATION 

CENTER, JAPAN; MUTAGENICITY TEST DATA OF EXISTING CHEMICAL 

SUBSTANCES BASED ON THE TOXICITY INVESTIGATION OF THE INDUSTRIAL 

SAFETY AND HEALTH LAW; (SUPPL), 1997] 



Metabolic Activation: RAT, LIVER, S-9, PHENOBARBITAL AND BETA-NAPHTHOFLAVONE 









Strain Indicator: TA100
























Results: NEGATIVE

























Test System: AMES SALMONELLA TYPHIMURIUM
























Dose: 0.0763-5000 UG/PLATE (TEST MATERIAL SOLVENT: WATER)

























SAFETY AND HEALTH LAW; (SUPPL), 1997]

Test System: E. COLI 

Strain Indicator: WP2UVRA 










Strain Indicator: WP2UVRA 










Strain Indicator: WP2UVRA/PKM101 


Method: PREINCUBATION








Strain Indicator: WP2UVRA/PKM101 









In Vivo Mutagenicity: 

Test System: BONE MARROW POLYCHROMATIC ERYTHROCYTES 

End Point: IN VIVO MICRONUCLEUS 

Species: MOUSE 

Strain/Sex: DDY/MALE 

Route: IP 

Dose: 100; 200; 400; 800 MG/KG (TEST MATERIAL SOLVENT: 0.5% 

CARBOXYMETHYLCELLULOSE SODIUM SALT) 

Dose Regimen: SINGLE DOSE; 24 HR HARVEST


Reference: [HAYASHI,M, KISHI,M, SOFUNI,T AND ISHIDATE MJR; MICRONUCLEUS TESTS 

IN MICE ON 39 FOOD ADDITIVES AND EIGHT MISCELLANEOUS CHEMICALS, 

FOOD CHEM. TOXICOL. 26(6):487-500, 1988] 

Test System: BONE MARROW POLYCHROMATIC ERYTHROCYTES 

End Point: IN VIVO MICRONUCLEUS 

Species: MOUSE 

Strain/Sex: DDY/MALE 

Route: IP 

Dose: 200 MG/KG (TEST MATERIAL SOLVENT: 0.5% CARBOXYMETHYLCELLULOSE 

SODIUM SALT) 

Dose Regimen: 1/D FOR 4D; 24 HR HARVEST 


Reference: [HAYASHI,M, KISHI,M, SOFUNI,T AND ISHIDATE MJR; MICRONUCLEUS TESTS 

IN MICE ON 39 FOOD ADDITIVES AND EIGHT MISCELLANEOUS CHEMICALS, 

FOOD CHEM. TOXICOL. 26(6):487-500, 1988] 

As taken from CCRIS powered by Toxnet, 2010 available at http://toxnet.nlm.nih.gov/cgibin/sis/htmlgen?CCRIS 

Genotoxicity [+ve, positive; -ve, negative; ?, equivocal; with, with metabolic activation; 

without, without metabolic activation] 

In vivo 

Species Test conditions Endpoint Result Reference 

Hamster 

s, 40 per 

group 

Hamster 

s, 40 per 

group 

Animals given a single gavage 

dose of 0 or 2.5 g/kg bw. 

Examination of micronuclei in 

bone marrow cells 

Intraperitoneal injection of 473 

mg/kg bw. Examination of 

micronuclei in bone marrow 

Chromosome damage -ve Basler, 1986 

Chromosome damage -ve Basler, 1986

Mice, 6 

males 

per 

group 

In vitro 

cells 

Intraperitoneal injections of 0, 

100, 200, 400 or 800 mg/kg bw. 

Examination of micronuclei in 

bone marrow cells 24 hr later. 

Chromosome damage -ve 

Good 

quality 

study 

Hayashi et al. 

1988 

Test system Test conditions Endpoint Activation Result References 

Human 

cells 

Chinese 

hamster 

lung cells 

Chinese 

hamster 

cells 

Chinese 

hamster 

cells 

Salmonella 

typhimuriu 

m 

TA92, 

TA94, 

TA98, 

TA100, 

TA1535, 

TA1537 

Salmonella 

typhimuriu 

m TA97, 

TA98, 

TA100, 

TA1535, 

TA1537 

Salmonella 

typhimuriu 

m TA98, 

TA100, 

TA102, 

TA104, 

Incubated at 

concentrations up 

to 0.01M. 

Incubated at 

concentrations up 

to 9 mg/ml for 48 

hr, cells examined 

for chromosomal 

aberrations and 

polyploidy. 

Concentrations up 

to 5 mg/ml. 

Examination for 

chromosomal 

aberrations 

Examination for 

sister chromatid 

exchanges 

Ames test with 

amounts up to 5 

mg/plate 



mg/plate 



mg/plate 

DNA damage with and without 

S9 

Chromosome 

damage and 

changes in 

chromosome 

number 

Chromosome 

damage 

Chromosome 

effects 

without S9 +ve for 

aberrations 

-ve for 

polyploidy 

with and without 

S9 

with and 

without S9 

Mutation with and without 

S9 


S9 


S9 

-ve Perocco et al. 

1983 

Ishidate et al. 

1984 

-ve Loveday et al. 

1990 

+ve 

(with S9 only) 

-ve 

Good quality 

study 

-ve 

Good quality 

study 

-ve 

Probably a 

good quality 

study to 

Japanese 

guideline 

Loveday et al. 

1990 

Ishidate et al. 

1984 

Zeiger et al. 

1992 

JETOC, 1997

TA1535, 

TA1537 

Escherichia 

coli 

WP2uvrA, 

WP2 

uvrA/pKM1 

01 

Bacillus 

subtilis 

strains 

M45, H17 

Concentrations up 

to 5 mg/plate 

Two rec assays 

measuring 

differential killing. 

Tested amounts 

not stated. 

GENE-TOX Evaluation B (post-1980): 


S9 

DNA damage 

(indicative test) 

Species/Cell Type: Mammalian polychromatic erythrocytes 

Assay Type: Micronucleus test, chromosome aberrations 

Assay Code: MNT- 

Results: Negative 

without 1 +ve 

1 -ve 

Panel Report: EMICBACK/77345; MUTAT RES 239:29-80,1990 

Reference: EMICBACK/63397; MUTAT RES 174:11-13,1986 

GENE-TOX Evaluation A (pre-1980): 

Species/Cell Type: Bacillus subtilis (H17 vs M45) 

Assay Type: Rec-assay, spot test, DNA effects (bacterial DNA repair) 

Assay Code: REWT 

Results: No conclusion 

Panel Report: EMICBACK/45048; MUTAT RES 87:211-297,1981 

-ve 

Probably a 

good quality 

study to 

Japanese 

guideline 

JETOC, 1997 

Nonaka, 

1989; Shirasu 

et al. 1976 

As taken from GENETOX powered by Toxnet, 2010 available at http://toxnet.nlm.nih.gov/cgibin/sis/htmlgen?GENETOX

Other In Vitro Test: 

Acorus calamus L. (AC), family Araceae, have been used in the Indian and Chinese systems of 

medicine for hundreds of years. The radix of AC is widely used in the therapy of diabetes in 

traditional folk medicine of America and Indonesia. AIM OF THE STUDY: To investigate the insulin 

sensitizing activity and antidiabetic effects of the ethyl acetate fraction of AC (ACE). MATERIALS AND 

METHODS: Glucose consumption mediated by insulin was detected in L6 rat skeletal muscle cells. 

Diabetes and its complications related indexes were monitored after orally administrating to 

genetically obese diabetic C57BL/Ks db/db mice daily for 3 weeks. RESULTS: ACE (12.5 and 25 

microg/ml) increased glucose consumption mediated by insulin in L6 cells (p

Remark: In vitro incubation of murine 3T3–L1 fibroblast–like cells with ethyl acetate for 72 h 

caused a reduction in final cellular protein content: ID50 = 43300 mg/l; FRAME 

kenacid blue test. 


Test substance: ethyl acetate diluted with water(170) 

Type: Cytotoxicity 

Remark: 

Tubulin assembly inhibition test In vitro incubation of 4.5 – 18 mg ethyl acetate/l with 

porcine brain tubulin inhibited the tubulin assembly: 4.5 mg/l: 0.280 total 

absorbance increment9 mg/l: 0.240, at 14.5 and 18 mg/l no saturation of the 

absorbance increment was reached during the 30–min incubation; 32 degree C; 

assembly was observed photometrically by measuring the increase in adsorbance 

at350 nm. 


(171) 

Type: Cytotoxicity 

Remark: Tubulin assembly inhibition test In vitro incubation of 13.5 g ethyl acetate/l with 

porcine brain tubulin caused 30 % inhibition of tubulin assembly, 37 degree C; pH 

6.9; assembly was observed photometrically by measuring the increase in absorbance 

at 350 nm. 



5.6 Carcinogenicity 

“Ethyl acetate exposure was associated with increased risk for lymphatic leukemia in rubber workers 

however, ethyl acetate is not generally regarded as a human carcinogen at the present time.” 


“Ethyl acetate was tested for carcinogenicity by pulmonary tumour response in strain A mice. It did 

not produce an increase in lung tumours compared with controls” As taken from NOHSC, available 

at http://www.nohsc.gov.au/OHSInformation/Databases/ExposureStandards/az/Ethyl_acetate.htm 

Carcinogenicity 

Species Test conditions Evidence of 

carcinogenicity 

Reference 

No studies meeting modern standards for carcinogenicity testing were identified. A limited study is summarized 

below. If required, data on ethanol and acetic acid, the two primary (hydrolysis) products of mammalian 

metabolism, could be summarised. 

Mice, 

strain A, 

15/sex in 

treated 

groups, 

50/sex 

untreated 

and 80/sex 

treated 

with 

vehicle 

Intraperitoneal injections of 150 or 750 mg/kg bw in 

tricaprylin given three times weekly for 8 wk to mice of 

a strain known to be susceptible to lung tumour 

induction. 

Limited study, only the lungs were examined in detail. 

Liver, kidneys, spleen, thymus, intestine and salivary 

and endocrine glands were also examined for 

“abnormalities”. 

Species: mouse 


Strain: other: A/He 

Route of admin.: i.p. 

Exposure period: 8 w 

Frequency of treatment: 3 times/w 

Post. obs. period: 16 w 

None 

No statistically significant 

increases in number of 

mice with lung tumours or 

number of lung 

tumours/mouse were 

observed after 24 wk in 

the surviving animals 

Stoner et al. 

1973

Doses: 150 mg/kg bw/injection (total dose: 3600 mg/kg bw) and 750 mg/kgbw/injection 

(total dose: 18000 mg/kg bw) 

Control Group: other: yes, concurrent vehicle and no treatment 

Method: other: Mouse Pulmonary Tumour Test according to Andervant and Shimkin 

Year: 1940 

GLP: no 

Test substance: other TS: vehicle: tricaprylin 

Result: Mortality: Low dose group: 3 of 30 (m/f) 

high dose group: 2 of 30 (only f) 

control group, vehicle: 6 of 160 (m/f) 

control group, untreated: 6 of 100 (m/f); 

number of mice with lung tumours: 

low dose group: 2 of 27 

high dose group: 7 of 28 

control group, vehicle: 37 of 154 

control group, untreated: 18 of 94; 

mean number of tumours per mouse: 

low dose group: 0.07 +– 0.02 (m) and 0.08 +– 0.02 (f) 

high dose group: 0.33 +– 0.09 (m) and 0.23 +– 0.06 (f) 

vehicle group: 0.24 +– 0.03 (m) and 0.20 +– 0.02 (f) 

untreated group: 0.22 +– 0.03 (f) and 0.17 +– 0.02 (f). 

Ethyl acetate did not produce an increase in lung tumours 

compared with controls. 



5.7 Irritation / immunotoxicity 

Skin, Eye and Respiratory Irritations: 

Irritating to mucous surfaces, particularly the eyes, gums and respiratory passages ... . On repeated or 

prolonged exposures, it causes conjunctival irritation and corneal clouding. .”


“118 subjects were exposed to a nail polish remover containing 16.5 % ethyl acetate; 1 ml was 

applied to the back of each subject with a brush applicator and was covered with an open patch for 

48 h; sites were then rinsed and evaluated: no reactions were observed in any of the subjects; 

procedure was repeated after the subjects had used the product (no further details) for 4 weeks: again 

no reactions were observed in the open patch test.” 

“25 subjects were patch-tested in a maximation test with 0.3 ml of a formulation containing 97 % 

ethyl acetate; occlusive test, five consecutive 48-hr periods; a challenge test 10 days after the final 

induction patch failed to elicit any skin reactions.” 

“Covered 24-h patch testing with undiluted ethyl acetate revealed that two of a group of six 

confectionery workers with occupational contact eczema reacted to ethyl acetate. Similar patch 

testing of 102 other eczema patients revealed one sensitized individual.” 


Sensitization 

No skin reactions were reported in a maximization test in 25 human volunteers following repeated 

covered 48-hr skin applications at a concentration of 10% in petrolatum (Kligman, 1972), or after five 

consecutive 48-hr covered patch tests with a formulation containing 97% ethyl acetate, with 

challenge 10 days later (Ivy Research Laboratories, 1983). 

No skin sensitization reactions were induced after “open patch” tests with a nail polish remover 

containing 16.5% ethyl acetate, applied to the back of 118 subjects for 48 hr, followed by 4 weeks of 

use of the product [no further details given], and open patch tests again using the same procedure 

(Epinette, 1987). 

Three skin sensitization reactions, and two equivocal reactions, were reported in 190 individuals 

following 24- or 48-hr covered patch tests with ethyl acetate at a concentration between 0.05 and 

0.5% in a cream base on 70 occasions over about 4 yr (Takenaka et al. 1970). A nail colour 

containing 6.5% ethyl acetate was applied undercover to the skin of the back of 218 subjects, 3 

days/week for 3 weeks, followed 14 days later by 2 consecutive 48-hr patch tests at a different site. 

Three insignificant responses were observed, although these were described as “irritant in nature 

possibly due to residual solvent on patches while under occlusion” (CTFA, 1980). 

Covered 24-hr patch tests with undiluted ethyl acetate revealed two reactions in a group of six 

confectionary workers with occupational eczema, and one reaction in 102 other eczema patients 

(Heygi, 1971) 

Skin Irritation 


Result: not irritating

Method: other: Skin Irritation 

GLP: no 


Remark: open application of 0.01 ml to the clipped skin of 5 rabbits; contact period: 24 h; 

injury grade 1 of 10 


Eye Irritation 


Result: not irritating 

Method: Draize Test 

Test substance: other TS: ethyl acetate in propylene glycol 

Remark: Instillation of 0.1 ml of 3, 10, 30 and 100 % vol.% test substance solution (2.7– 90 

mg ethyl acetate) into one eye of 4 – 6 rabbits; mean 24 h post instillation 

Draize score: 2/110 – 15/110 (dose–related); results classified according to the Texaco single–digit 

toxicity classification system:minimally (= mildly) irritating; corneal thickness 

measurement: percentage of swelling at 24 h post installation compared to several 

hours before installation (100 % corneal thickness) = 99 – 106 % (not dose–related), 

result was noted as mild. 



Method: other: Eye Irritation 

Year: 1946 

GLP: no 

(142) 

Remark: application of 0.005 – 0.5 ml ethyl acetate to the center of the cornea; examination

after 18 – 24 h; injury grade 2 of 10 (not classifiable according to current 

day standards) 



(122) 

Method: other: Instillation of one drop into eye (no further details) 

Remark: Reddening and slight swelling of the conjunctiva; symptoms were reversible after one 

to two days. 


Species: human 

Result: irritating 

EC classificat.: not irritating 

Year: 1943 

Remark: Dose: 400 ppm; 

Time: 72 hour. 

Source: Petrasol B.V. Gorinchem(2) 

Sensitization 

Type: Guinea pig maximization test 

Species: guinea pig 

Result: not sensitizing 

Method: OECD Guide–line 406 "Skin Sensitization" 

Year: 1981 

Test substance: other TS: refer to Huls Section 1 dossier.


Type: other 

Species: human 

Result: not sensitizing 

Classification: not sensitizing 

Remark: A maximum test was carried out on 25 volunteers. The material was tested at a 

concentration of 10% in petrolatum and produced no sensitization reactions. 

Source: Petrasol B.V. Gorinchem (5) 

HUMAN CASE: 

Remark: 

Occlusive epicutaneous testing of 190 individuals identified three sensitized 

individuals and another two giving equivocal reactions (mild erythema); vehicle 

control tests were always carried out simultaneously; undisclosed concentration 

between 0.05 and 0.5 % in a cream base; contact period: 24 or 48 h; 70 occasions 

between September 1963 and December 1967. 


Remark: 

Covered 24–h patch testing with undiluted ethyl acetate revealed that two of a group 

of six confectionery workers with occupational contact eczema reacted to ethyl 

acetate. Similar patch testing of 102 other eczema patients revealed one sensitized 

individual. 


Remark: 

A woman who developed contact dermatitis of the nose as a result of wearing 

spectacles reacted positively in an occlusive patch test (presumably for 24 – 48 h) with 

ethylene glycol monomethyl ether acetate and >= 0.1 % ethyl acetate in methyl 

ethyl ketone; she did not react to 0.01 % ethyl acetate; fifteen healthy control subjects 

failed to react at 5 %; the spectacles did not contain any ethyl acetate, but ethylene 

glycol monomethyl ether acetate as an optical solvent with an ethyl acetate–like 

molecular shape. 


Remark: 

Application of ethyl acetate to (probably) three volunteers for 1 h/d for 6 days resulted 

in damage to the outer skin layer (stratum corneum), as measured by an increase in 

the rate of water vapour loss from the skin; test substance was applied in a glass 

cylinder with a 2 cm2 opening, fixed by agar agar. 


Remark: 

Twelve volunteers of Oriental ancestry were patch tested with a 25 % aqueous 

solution of ethyl acetate; 25 ul were applied to the forearm on a filter paper patch 

and covered for 5 min; the patches were removed and the sites were observed for 60 

minutes: erythema was seen in one of the subjects. 


Remark: 

Ten people (mixed sexes) were exposed to various 

concentrations of ethyl acetate vapour for 3 – 5 minutes in 

a gas cabinet; after exposure, each individual classified 

the effect of the vapour on the eyes, nose and throat: a 

concentration of 400 ppm (1464 mg/m3) irritated the eyes, 

nose and throat of the majority of subjects. 


Remark: 

A product containing 97 % ethyl acetate was evaluated in 10 

subjects: 21 consecutive applications of 0.1 ml were made to 

the back of each subject under closed patches; each patch 

was removed after 23 h and the product was rinsed from the 

skin; sites were scored 1 h later; there was no evidence 

of cumulative skin irritation. 


Remark: 

Ethyl acetate is unlikely to cause irritation on brief 

occasional exposure. Prolonged or repeated contact will 

defat the skin and may cause irritation and dermatitis. 

Unlikely to be absorbed across the skin in harmful amounts. 


Remark: 

Liquid ethyl acetate and high concentrations of the vapour 

will produce conjunctival irritation and transient corneal 

damage.



5.8 All other relevant types of toxicity 

Human Case Report: 

The tissue distribution of ethyl acetate and ethanol in a case of acute intoxication by ethyl acetate is 

presented. The victim was a 39-year-old man who was found dead lying on his abdomen in the 

interior of a tank containing ethyl acetate. Confirmation of ethyl acetate was obtained with static 

headspace gas chromatography with mass spectrometry. In blood, rapid biotransformation of ethyl 

acetate occurs by plasma esterases resulting in acetic acid and ethanol. Quantitation of ethyl acetate 

and ethanol in the postmortem samples was performed using static headspace gas chromatography 

with flame ionization detector. N-butanol was used as internal standard. Separation of the 

compounds was obtained on a Supelcowaxtrade mark-10 Fused Silica capillary column. The method 

was linear over the specific ranges investigated and showed a within-run accuracy of 99.8 and 

101.0% and a precision of 0.5 and 2.0% for ethanol and ethyl acetate, respectively. The postmortem 

samples were analyzed in duplicate or triplicate. Coefficients of variation were < or =4.51% for ethyl 

acetate and < or =0.52% for ethanol. The low ratios of the ethyl acetate concentration to the 

ethanol concentration found in the postmortem tissue samples confirmed the rapid in vivo 

biotransformation of ethyl acetate. The highest concentration of ethyl acetate was found in the testis 

indicating that postmortem percutane absorption may have occurred. To our knowledge, this is the 

first reported tissue distribution study of ethyl acetate and ethanol in a case of acute intoxication by 

ethyl acetate. 

As taken from Coopman VA et al. Forensic Sci Int. 2005, Nov 25; 154(2-3):92-5. PubMed, 2010 

available at 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=16182954&d 

opt=AbstractPlus 

6. Functional effects on 

6.1 Broncho/pulmonary system 

Type: other: Upper–respiratory–tract irritation 

Remark: 

Concentration of airborne ethyl acetate that produced a 50 % 

decrease in respiratory rate in mice, RD50 = 2.25 mg/l; 

inhalation exposure period: 10 min; 4 male mice/concentra– 

tion. 


Test substance: reagent quality 

Type: other: Upper–respiratory–tract irritation 

Remark: 

Concentration of airborne ethyl acetate that produced a 50 % 

decrease in respiratory rate in mice, RD50 = 2.12 mg/l; 

inhalation exposure period: ca. 5 min; 6 mice/concentration. 


Remark: 

10 volunteers (men and women, between 18 and 25 years old) 

were exposed to 344 – 501 mg ethyl acetate/m3 air for 4 h: 

respiratory uptake (%): 63.2 +– 5.4 (men) 

56.7 +– 1.7 (women) 

respiratory excretion (%): 3.0 +– 0.6 (men) 

2.5 +– 0.6 (women) 

respiratory retention (%): 60.2 +– 8.6 (men) 

54.1 +– 5.4 (women); 

concentrations in environmental and expired air were 

measured every hour during exposure (expired air was 

collected during 3 min); 

rate constant of respiratory elimination during the first 

hour after cessation of the ethyl acetate exposure: 4.66 h–1 

(men) and 4.92 h–1 (women); 

respiratory elimination compared to retained ethyl acetate 

after cessation of exposure: 0.2 %; one hour after cessation 

of exposure ethyl acetate was undetectable in the expired 

air, therefore the authors suggested a rapid biotransfor– 

mation. 

Source: BP Chemicals Ltd. London(182) (183) 


6.2 Cardiovascular system 

“Leucopenia without change in differential or red blood cell counts was observed in rats exposed for 

4 hr to increasing air concentration of ... ethyl acetate. ... This effect was abolished by adrenalectomy. 

This solvent caused leucopenia only when exposure reached the irritant level. It is discussed that 

stress associated with the irritative effect of chemicals can confound specific hematological effects.” 

“Anti-Arrhythmia Agents” 


Type: other: Myocardial depressant action 

Remark: 

In vitro incubation with ca. 2640 mg/l ethyl acetate 

depressed the force of guinea pig ventricular strip 

contraction: ca. 80 % loss of peak tension (= negative 

inotropic action; data obtained from a figure). 



6.3 Nervous system 

The neurotoxic effects of inhaled amyl-acetate, ethyl-acetate, and n-butyl-acetate were investigated in 

mice. Male CFW-albino-mice were exposed to up to 40,000 ppm amyl-acetate, 2,000 ppm ethylacetate, 

or 8,000 ppm n-butyl-acetate for 20 minutes in an exposure chamber. Acute neurotoxic 

effects were assessed by measuring locomotor activity and functional observational battery. Similar 

acute behavioral effects on locomotor activity were observed in mice following ethyl-acetate and nbutyl-acetate 

exposure, with amyl-acetate inducing little neurotoxic effect. Exposure to the 

compounds caused changes in posture, with decreased arousal and rearing; increased central nervous 

system excitability, as manifested by increased tonic and clonic movements; and increased autonomic 

effects. Also, decreased mobility and righting reflex, and an elevated reaction to sensory stimuli were 

observed. Handling induced convulsions were produced in some mice following acute exposure; 

potency differences were observed. Significant decreases in locomotor activity were seen with 

exposure to ethyl-acetate and n-butyl-acetate at the highest concentrations tested, and minimally 

effective levels for activity decreasing effects were 2,000 and 8,000 ppm for ethyl-acetate and nbutyl-acetate, 

respectively. Rapid recovery was seen in mice after removal from exposure. /It was/ 

concluded that acute exposure to acetyl-acetate, n-butyl-acetate, and ethyl-acetate produces acute 

neurobehavioral effects which differ from the effects produced by exposure to alkylbenzenes and

halogenated hydrocarbon solvents. [Bowen SE, Balster RL; Fundam and Appl Toxicol 35 (2): 189-96 

(1997)] **PEER REVIEWED** 

ANIMAL EXPERIMENTS HAVE SHOWN THAT, IN VERY HIGH CONCN, THE ESTER HAS ... /SRP: 

CNS DEPRESSANT/ & LETHAL EFFECTS. 

[International Labour Office. Encyclopedia of Occupational Health and Safety. Volumes I and II. New 

York: McGraw-Hill Book Co., 1971., p. 477] **PEER REVIEWED** 

“THE ALIPHATIC ESTERS USED AS LACQUER SOLVENTS, PRIMARILY ETHYL ACETATE AND 

BUTYL ACETATE, HAVE ... /SRP: CNS DEPRESSANT/ PROPERTIES WHICH ARE LESS PROMINENT 

THAN THOSE ASSOCIATED WITH THE CHLORINATED HYDROCARBONS.” 

“Chronic exposure to solvent mixtures including ethyl acetate has been associated with poorer 

performance on neurobehavioral tests. High concentrations orally administered to rabbits caused lack 

of coordination. High concentrations have intoxicating properties in animals and would be expected 

to cause narcosis in humans.” 

“Cats exposed to a concn of 12,000 ppm in 43 mg/l for 5 hr were affected by the lowest /SRP: CNS 

depressant/ concn. Exposures to 20,000 ppm in 72 mg/l for 45 min resulted in deep /SRP: CNS 

depression/, recovery. Exposures to 43,000 ppm in 155 mg/l for 14-16 min resulted in deep /CNS 

depression/, death.” 


“In 1931, a fatality was reported. A workman was found dead in the interior of a tank in which he 

was using a paint containing ethyl acetate but also other constituents. Death resulted from narcosis or 

anoxia.” As taken from NOHSC, available at 

http://www.nohsc.gov.au/OHSInformation/Databases/ExposureStandards/az/Ethyl_acetate.htm 

“An ethyl acetate extract of Spigelia anthelmia (EASa), with validated anthelmintic activity, was 

evaluated for its acute toxicity and general effects in albino Swiss mice and for neuromuscular 

relaxant activity in the frog sciatic-gastrocnemius and rectus abdominis preparation. The extract 

induced a dose-related myotonia and muscular paralysis of rapid onset at higher doses. The 

calculated LD50 after oral and intraperitoneal administration was 345.9 [241.4-484.7] mg/kg and 

60.8 [47.4-80] mg/kg, respectively. In broilers, intramuscular injection of EASa-induced spastic 

paralysis qualitatively similar to that obtained after succinylcholine administration and contrasting to 

the flaccid paralysis induced by D-tubocurarine. The contraction elicited by direct stimulation of the 

gastrocnemius was blocked by EASa by 54.3+/-4.7% (IC50 = 21.4 [11.2-35.8] microg/ml) and the 

twitches evoked by stimulation of the sciatic nerve were blocked by 69.1+/-7.4% (IC50 = 17.9 [4.5- 

34.23] microg/ml). EASa also blocked acetylcholine-induced contractions in the frog rectus abdominis 

by 58.6+/-7.4% (IC50 = 7.4 [1.7-15.28] microg/ml) but did not decrease tonic contractions induced 

by a high-potassium Ringer solution. In summary, the ethyl acetate extract of Spigelia anthelmia 

induces tonic paralysis in vivo, and decreases amplitudes of twitches and increases tonus of skeletal 

muscle in vitro.” 

As taken from Camurca-Vasconcelos AL et al., (2004), J Ethnopharmacol. 2004 Jun; 92(2-3):257-61, 

available at

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uid 

s=15138009&query_hl=4&itool=pubmed_docsum 

“Various effects on the central and peripheral nervous system have been reported in workers exposed 

for several years-(often 5-15 yr) to concentrations, where specified, of about 0.03-0.2 mg ethyl 

acetate/L The effects seen included reductions in nerve conduction velocity, decreased ability to 

concentrate, impaired memory and subjective symptoms indicative of CNS depression. It is difficult to 

attribute these effects to ethyl acetate exposure, however, since the workers were also exposed to a 

variety of other solvents (including n-hexane, toluene, styrene, xylene, trichloroethylene and methyl 

ethyl ketone) which can induce nervous system toxicity (Hanninen et al. 1976; Husman, 1980; Mutti 

et al. 1982; Olson, 1982; Triebig et al. 1983).” As taken from BIBRA (1992). 

In rats exposed by inhalation at 0, 350, 750, or 1500 ppm, 6 hr/day, 5 days/week, for 13 weeks, 

motor activity (movement duration) was reduced in female rats at the highest concentration (the 

animals were normal after a 4-week recovery period). No other effects on motor activity (number of 

movements), or in functional observational battery tests (including grip strength and foot splay), or on 

nervous system tissues (on microscopic examination) were reported in male or female rats exposed to 

up to 1500 ppm (Christoph et al. 2003). 

Following a 10-day inhalation exposure, a reduction in motor activity was reported in female rats at 

6000 ppm, and a functional observational battery (FOB) test suggested that males and females 

exposed to 3000 or 6000 ppm may have experienced deficits in general conditioning and pupil size 

(Anon, 1995a). Decreased activity was reported in rats exposed at 3000 and 6000 ppm [duration 

unspecified]; no effects were noted at 1500 ppm (Anon, 1995b). 

In mice, central nervous system (CNS) depression developed after exposure for 3-5 hr at 5000 ppm 

(18 mg/l) (Boeltzig, 1931), and after 30 minutes to 560 ppm [2 mg/l], but not at 300 ppm [1.1 mg/l] 

(Glowa & Dews, 1987). No narcotic symptoms were induced in mice inhaling 15-16 mg/l, 6 hr/day, 

for 1 wk (Flury & Wirth, 1933). Neurobehavioural effects, measured by FOB tests, and decreased 

locomotor activity were observed in mice after a 20-minutes inhalation exposure at 2000 ppm 

(Bowen & Balster, 1997). 

ND 50 (narcotic dose) of 4.5 g/kg for rabbits (this is the single dose given by stomach tube that 

produced stupor and loss of voluntary movements in half of the animals) (Munch, 1972). In two early 

studies, inhalation of the vapours of ethyl acetate [not further defined] resulted in deep narcosis (and 

subsequent death) of rabbits within 9 minutes (Weber, 1902), and air ‘saturated’ with ethyl acetate 

for 5 minutes induced deep narcosis in guinea pigs (Althoff, 1931). Exposure at 21,500 ppm (77 mg/l) 

for 1-10 hr was fatal to guinea pigs, causing death due to severe CNS depression (Blina, 1933a,b). 

In cats, concentrations of approximately 35 mg/l (where specified, for 7.5-24 hr) produced excessive 

salivation (Boeltzig, 1931; Flury & Wirth, 1933). Levels of 72 mg/l for 45 minutes (Boeltzig, 1931) and 

43 mg/l for 3-5 hr (Flury and Wirth, 1933) induced deep narcosis, whereas 56 mg/l (for 60-72 

minutes) caused fatigue, stupor and death (Flury & Wirth, 1933). 

Type: Neurotoxicity

Remark: 

Threshold limit for a depressive effect of ethyl acetate on the vestibulo–oculumotor 

reflex in female Sprague–Dawley rats: 44 mg/l blood (blood–level caused by an 

intravenous infusion at a rate of 18.5 mg ethyl acetate/kg/min during 60 min). 



vehicle: Intralipid (trade mark; lipid emulsion used for 

human parenteral nutrition) 

(176) 

Type: Neurotoxicity 

Remark: 

Two intravenous injections of 120 mg/kg bw (0.2 ml/rabbit of 

1.5 kg; 30–min interval) caused narcosis in a rabbit. 



Remark: Oral narcotic dose for rabbits, ND50 = 4493 mg/kg bw. 



Remark: 

Narcotic threshold concentration for mice: 18 mg/l byinhalation; deep narcosis 

occurred after 190 – 240 min ofexposure. 


Type: Neurotoxicity

Remark: 

Narcotic threshold concentration for cats: 43 mg/l by 

inhalation; deep narcosis occurred after ca. 300 min of 

exposure. 


Remark: 

Inhalation of high concentrations may cause central nervous system depression, 

resulting in drowsiness and loss of consciousness. 


Remark: 

Major effects of acute over–exposure will be local irritation, CNS depression and 

acidosis. Prolonged exposure to concentrations above the occupational expsure 

standard have been reported to cause anaemia, liver and kidney damage. 



6.4 Other organ systems, dependent on the properties of the substance 

Human Case Report: 

Remark: 

A man died from inhaling, in an enclosed space, the vapour 

from a lacquer containing 80 % ethyl acetate. Examination at 

autopsy revealed hyperaemia of the upper respiratory tract, 

spleen and kidneys; petechial haemorrhages in the 

epicardium and pleura and haemorrhagic gastritis. 


Remark: 

Inhalation of ethyl acetate vapour at concentrations above 

2000 ppm (7320 mg/m3) may cause narcosis. 


Remark: 

Local effects include temporary, slight corneal clouding and inflammation of the gums 

after inhalation of the vapours. 


Remark: 

Ingestion of large amounts may cause gastrointestinal irritation and central nervous 

system depression, leading to loss of consciousness. Aspiration during swallowing or 

vomiting will injure the lungs. 


Remark: 

Study of 30 workers exposed chronically to 15–50 mg of ethylacetate in addition to 

20 to 80 mg of amyl acetate/L of air showed no abnormalities in cornea, merely 

hyperemia of bulbar conjunctiva. Prolonged inhalation may be damaging lungs, liver, 

kidney and heart. 



7. Addiction 

JTI is not aware of any internal or external information that demonstrates that this ingredient 

enhances the uptake, the metabolism of nicotine, or reinforces the addictive effect of nicotine in 

tobacco.

8. Burnt ingredient toxicity 

This ingredient was considered as part of an overall safety assessment of ingredients added to tobacco 

in the manufacture of cigarettes. An expert panel of toxicologists reviewed the open literature and 

internal toxicology data of 5 tobacco companies to evaluate a composite list of ingredients used in the 

manufacture of cigarettes. The conclusion of this report was that these ingredients did not increase 

the inherent biological activity of tobacco cigarettes, and are considered to be acceptable under 

conditions of intended use (Doull et al., 1994 & 1998). 

8.1 Neat ingredient 

No data available to us at this time. 

8.2 Smoke chemistry 

A number of experimental cigarettes were prepared containing flavoring ingredients in combination. 

One of these cigarettes contained Ethyl acetate at 643 ppm (Baker et al., 2004a). Results showed 

that the addition of the ingredients had no impact on smoke chemistry when compared to a 

reference cigarette. 

Test cigarettes, including various combinations of ingredients, were compared to identical, additive 

free, reference cigarettes in a smoke chemistry study. One experimental cigarette contained Ethyl 

acetate at 515 ppm, in addition to over 160 other ingredients (Carmines, 2002). The main 

differences, when compared to the reference cigarette, were an increase in water, and decreases in 

nicotine, nitrogen oxides, formaldehyde, phenols, acrylonitrile, naphthalene, N-nitrosamines, and 

arsenic (Rustemeier et al., 2002). 

A test cigarette, with a combination of flavors, was compared to identical, reference cigarette without 

flavors in a smoke chemistry study. The test cigarette included Ethyl acetate at 13 and 600 ppm. 

Results are given in JTI KB Study Report (s). 

8.3 Condensate in vitro toxicity 

Tobacco smoke condensates from cigarettes containing ingredients and an “ingredient free” reference 

were tested in a battery of in vitro tests (the Ames test, neutral red cytotoxicity assay). Within the 

sensitivity and specificity of the bioassays the activity of the condensate was not changed by the 

addition of the ingredients, which included Ethyl acetate at 515 ppm (Carmines, 2002). 


were tested in a battery of in vitro tests (the Ames test, mammalian cell micronucleus test and the 

neutral red cytotoxicity assay). Within the sensitivity and specificity of the bioassays the activity of the 

condensate was not changed by the addition of the ingredients, which included Ethyl acetate at 643 

ppm (Baker et al., 2004c).

The effects of the presence of a number of ingredients, including Ethyl acetate at 515 ppm, in test 

cigarettes were evaluated in a bacterial mutagenicity assay of cigarette smoke condensate. Results for 

the test cigarettes were compared those of an ingredient-free reference cigarette. Within the 

sensitivity and specificity of the test systems, the in vitro mutagenicity of the cigarette smoke was not 

increased by the addition of the ingredients (Röemer et al., 2002). 

A neutral red assay was performed on both cigarette smoke condensate and the water soluble portion 

of the gas/vapor phase of a test cigarette containing Ethyl acetate at 515 ppm. Results for the test 

cigarettes were compared those of an ingredient-free reference cigarette. Within the sensitivity and 

specificity of the test systems, the in vitro cytotoxicity of the cigarette smoke was not increased by the 

addition of the ingredients (Röemer et al., 2002). 

The effects of the presence of a number of flavor ingredients, including Ethyl acetate 13 and 600 

ppm, in test cigarettes were evaluated in a bacterial mutagenicity assay of cigarette smoke 

condensate. Results for the test cigarettes were compared those of a reference cigarette without 

flavors. Results are given in JTI KB Study Report (s). 

The effects of the presence of a number of flavor ingredients, including Ethyl acetate 600 ppm, in test 

cigarettes were evaluated in a cytotoxicity assay of cigarette smoke condensate. Results for the test 

cigarettes were compared those of a reference cigarette without flavors. Results are given in JTI KB 

Report (s). 


were tested in a battery of in vitro tests (the Ames test, mammalian cell micronucleus test and the 

neutral red cytotoxicity assay). Within the sensitivity and specificity of the bioassays the activity of the 

condensate was not changed by the addition of the ingredients, which included Ethyl acetate at 350 

ppm. Results are given in fGLH Study Report (2010). 

8.4 Condensate in vivo toxicity 

When evaluated in a 90-day sub-chronic inhalation study, the response due to tobacco smoke 

exposure was not distinguishable between test and control cigarettes, indicating that the presence of 

ingredients, including Ethyl acetate at 643 ppm, had made no discernable differences to the type and 

severity of the treatment related changes (Baker et al., 2004c). 

The effects of adding Ethyl acetate at 515 ppm, in combination with other ingredients in a series of 

test cigarettes, were evaluated in a 13-week inhalation study, in which the test cigarettes were 

compared to an ingredient free reference cigarette. The results demonstrated that the addition of the 

ingredients did not increase the overall toxicity of the test cigarette smoke, when compared to that of 

the reference cigarette (Vanscheeuwijck et al., 2002). 

When evaluated in a 90-day sub-chronic inhalation study, the response due to tobacco smoke 

exposure was not distinguishable between test and control cigarettes, indicating that the presence of

ingredients, including Ethyl acetate at 515 ppm, had made no discernable differences to the type and 

severity of the treatment related changes (Carmines et al., 2002). 

The cigarette smoke condensate from test cigarettes containing a number of ingredients in 

combination, including Ethyl acetate at 13 and 600 ppm, was evaluated in a mouse skin painting 

assay and compared to the condensate of a reference cigarette without flavorings. It was concluded 

that the test cigarette had no greater tumor promotion potential than the reference cigarette. Results 

are given in JTI KB Study Report (s). 

The effects of adding Ethyl acetate 13 and 600 ppm to a test cigarette, in combination with other 

flavorings, were evaluated in a 13-week inhalation study, in which the test cigarette was compared to 

a flavour free reference cigarette. The results did not indicate any consistent differences in toxicity 

between smoke from the test and reference cigarettes. Results are given in JTI KB Study Report (s). 

The effects of adding Ethyl acetate at

water, based upon ethyl acetate's biodegradation in aqueous screening studies. 93% biodegradation 

was observed in a complete mix continuous-flow activated sludge system. 26.6 and 57.1% of ethyl 

acetate's theoretical BOD was reached in 5 days using the standard dilution method and seawater 

dilution method, respectively. If released into water, ethyl acetate is not expected to adsorb to 

suspended solids and sediment in water based on the estimated Koc. Volatilization from water 

surfaces is expected to be an important fate process based on ethyl acetate's Henry's Law constant. 

Estimated volatilization half-lives for a model river and model lake are 8.9 hours and 5.6 days, 

respectively. An estimated BCF of 3.2 suggests the potential for bioconcentration in aquatic organisms 

is low. Ethyl acetate's hydrolysis half-life at 25 deg C and pH 7 is 2.0 years. Occupational exposure to 

ethyl acetate may occur through inhalation and dermal contact with this compound at workplaces 

where ethyl acetate is produced or used or where adhesives, thinners, degreasers, paints, inks, and 

dome reagents are used. The general population may be exposed to ethyl acetate via inhalation of 

ambient air, ingestion of food and drinking water, or dermal contact with consumer products 

containing this compound. (SRC) **QC REVIEWED** 

Probable Routes of Human Exposure: NIOSH (NOES Survey 1981-1983) has statistically estimated 

that 375,906 workers (87,691 of these are female) are potentially exposed to ethyl acetate in the 

US(1). Occupational exposure to ethyl acetate may occur through inhalation and dermal contact with 

this compound at workplaces where ethyl acetate is produced or used(SRC). Ethyl acetate was 

identified (relative abundance) in air samples collected where printing pastes (66%) and paints (30%) 

were used, in car repair shops (45%), and in various other industries (57%) in Belgium(2). Mean 

concentrations of ethyl acetate in air during parquet work in Finland were 119 ppm during 

installation with resin adhesives; 319 ppm during puttying; 72 ppm during sanding after puttying; 413 

ppm during undercoat varnishing (nitrocellulose); 64 ppm during urea-formaldehyde varnishing; and 

1 ppm during work with water-based varnishes(3). It was also detected in air during the use of contact 

adhesives at mean concentrations of 14 ppm during repair of a textile carpet (dispersion and contact 

adhesives); 83 ppm during repair of a textile carpet (contact adhesives only); 29 ppm during beading 

of textile carpets (contact adhesives only); and 71 ppm during repair of bathroom floor mats 

(dispersion and contact adhesives)(3). Ethyl acetate was detected in 36% of all air samples, at a mean 

concentration of 11 ppm, collected from Finnish furniture factories from 1975 to 1984(4). Breathing 

zone samples collected during spray painting contained ethyl acetate at a geometric mean 

concentration of 9.51 ppm(5). It was detected in the air of one auto paint shop at a concentration of 

10.5 mg/cu m(6). Ethyl acetate was identified in 12% of 275 products (including thinners, degreasers, 

paints, inks, and dome reagents) used in workplaces in various industries(7). Ethyl acetate was 

identified in the breathing zone of shoe factory workers(8). Ethyl acetate was detected in the ambient 

air of shoe factory in Italy in Nov 1991 at median concentrations of 10 and 7 mg/cu m(9). 

[(1) NIOSH; National Occupational Exposure Survey (NOES) (1983) (2) Veulemans H et al; Am Indust 

Hyg Assoc J 48: 671-7 (1987) (3) Riala REE, Riihimaki HA; Appl Occup Environ Hyg 6: 301-8 (1991) 

(4) Priha E; Ann Occup Hyg 30: 289-94 (1986) (5) Myer HE et al; Am Ind Hyg Assoc J 54: 663-70 

(1993) (6) Medinilla J, Espigares M; Ann Occup Hyg 32: 509-13 (1988) (7) Lehman E et al; pp. 31-41 

in Safety and Health ASP Org Sol Expos Finland April 1985, Riihimaki V, Ulfvarson U, eds NY,NY: 

Alan R Liss Inc (1986) (8) Ahonen I, Schimberg RW; Br J Ind Med 45: 133-6 (1988) (9) Mutti A et al; 

Int Arch Occup Environ Health 65: S171-6 (1993)] **PEER REVIEWED**

The general population may be exposed to ethyl acetate via inhalation of ambient air, ingestion of 

food and drinking water, and dermal contact with consumer products containing ethyl acetate. (SRC) 

**PEER REVIEWED** 

Body Burden: Mother's milk from 4 urban areas in the USA, 1 of 8 samples positive(1). 7 out of 12 

breath samples collected from nine volunteers in Bayonne and Elizabeth, NJ between July and Dec 

1980 contained ethyl acetate at unreported concentrations(2). Ethyl acetate was identified as a 

component in 13.7% of expired air samples from 54 volunteers in the Chicago area at a geometric 

mean concentration of 0.447 ng/l(3). Ethyl acetate was detected in expired air samples from 5 of 8 

male volunteers at levels ranging from 0.30 to 190.0 ug/hr(4). 

[(1) Pellizzari ED et al; Environ Sci Technol 16: 781-5 (1982) (2) Wallace LA et al; Environ Res 35: 

293-319 (1984) (3) Krotoszynski BK et al; J Anal Toxicol 3: 225-34 (1979) (4) Conkle JP et al; Arch 

Environ Health 30: 290-5 (1975)] **PEER REVIEWED** 

Natural Pollution Sources: Ethyl acetate is a natural product of fermentation(1,2). Natural sources of 

ethyl acetate include animal waste, plant volatiles, and microbes(1). 

[(1) Graedel TE; Chemical Compounds in the Atmosphere. NY,NY: Academic Press pp. 223-34 

(1978) (2) Reed G; Kirk-Othmer Encycl Chem Tech; 3rd ed NY,NY: Wiley Interscience 24: 789 

(1983)] **PEER REVIEWED** 

Artificial Pollution Sources: Ethyl acetate's production and use as a pharmaceutic aid (flavor); in 

artificial fruit essences; as a solvent; in the manufacture of smokeless powder, artificial leather, and 

photographic films and plates; and in cleaning textiles(1) may result in its release to the environment 

through various waste streams(SRC). 

[(1) Budavari S; The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 12th ed. 

Whitehouse Station, NJ: Merck and Co Inc p 641 (1996)] **PEER REVIEWED** 

Environmental Fate: TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc 

value of 59(SRC), determined from a log Kow of 0.73(2) and a regression-derived equation(3), 

indicates that ethyl acetate is expected to have high mobility in soil(SRC). Volatilization of ethyl 

acetate from moist soil surfaces is expected to be important(SRC) given a Henry's Law constant of 

1.34X10-4 atm-cu m/mole(4). The potential for volatilization of ethyl acetate from dry soil surfaces 

may exist(SRC) based on a vapor pressure of 93 mm Hg(5). Ethyl acetate may biodegrade in soil(SRC), 

based upon its biodegradation in aqueous screening studies(6,7). 

[(1) Swann RL et al; Res Rev 85: 23 (1983) (2) Hansch C et al; Exploring QSAR. Hydrophobic, 

Electronic, and Steric Constants. ACS Professional Reference Book. Heller SR (consult ed) 

Washington,DC: Amer Chem Soc p. 9 (1995) (3) Lyman WJ et al; Handbook of Chemical Property 

Estimation Methods. Washington,DC: Amer Chem Soc pp. 4-9 (1990) (4) Butler JAV, Tamchandani 

CN; J Chem Soc: 952-5 (1935) (5) Daubert TE, Danner RP; Physical and Thermodynamic Properties 

of Pure Chemicals: Data Compilation. Design Inst Phys Prop Data, Amer Inst Chem Eng., NY,NY: 

Hemisphere Pub Corp, Vol 2 (1991) (6) Takemoto S et al; Suishitsu Odaka Kenkyu 4: 80-90 (1981) 

(7) Kincannon DF et al; J Water Pollut Control Fed 55: 157-63 (1983)] **PEER REVIEWED** 

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 59(SRC), determined 

from a log Kow of 0.73(2) and a regression-derived equation(3), indicates that ethyl acetate is not 

expected to adsorb to suspended solids and sediment in water(SRC). Ethyl acetate is expected to 

volatilize from water surfaces(3,SRC) based on a Henry's Law constant of 1.34X10-4 atm-cu 

m/mole(4). Estimated volatilization half-lives for a model river and model lake are 8.9 hours and 5.6

days, respectively(3,SRC). According to a classification scheme(5), an estimated BCF of 3.2(3,SRC), 

from the log Kow(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). 

Simple esters are resistant to hydrolysis; ethyl acetate's hydrolysis half-life at 25 deg C and pH 7 is 2.0 

years(6). Biodegradation is expected to be an important process in aquatic systems(SRC), based upon 

aqueous screening studies(7,8). Ethyl acetate reached 26.6 and 57.1% of its theoretical BOD in 5 

days using the standard dilution method and seawater dilution method, respectively(7). 99.9% 

removal of ethyl acetate was observed in a complete mix continuous-flow activated sludge system; 

93% of this removal was attributed to biodegradation(8). 94% of theoretical methane production was 

observed after incubation in sediment and groundwater collected from the methanogenic portion of 

an anoxic aquifer polluted by municipal landfill leachate(9). 

[(1) Swann RL et al; Res Rev 85: 23 (1983) (2) Hansch C et al; Exploring QSAR. Hydrophobic, 

Electronic, and Steric Constants. ACS Professional Reference Book. Heller SR (consult ed) 

Washington,DC: Amer Chem Soc p 9 (1995) (3) Lyman WJ et al; Handbook of Chemical Property 

Estimation Methods. Washington,DC: Amer Chem Soc pp. 4-9, 5-4, 5-10, 15-1 to 15-29 (1990) (4) 

Butler JAV, Tamchandani CN; J Chem Soc: 952-5 (1935) (5) Franke C et al; Chemosphere 29: 1501- 

14 (1994) (6) Mabey WR et al; J Phys Chem Ref Data Vol 7, No. 2 p. 411 (1978) (7) Takemoto S et 

al; Suishitsu Odaka Kenkyu 4: 80-90 (1981) (8) Kincannon DF et al; J Water Pollut Control Fed 55: 

157-63 (1983) (9) Sulfita JM, Mormile MR; Environ Sci Technol 27: 976-8 (1993)] **PEER 

REVIEWED** 

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic 

compounds in the atmosphere(1), ethyl acetate, which has a vapor pressure of 93 mm Hg at 25 deg 

C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase ethyl acetate is 

degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the 

half-life for this reaction in air is estimated to be 10 days(3,SRC). 

[(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988) (2) Daubert TE, Danner RP; Physical and 

Thermodynamic Properties of Pure Chemicals: Data Compilation. Design Inst Phys Prop Data, Amer 

Inst Chem Eng., NY,NY: Hemisphere Pub Corp, Vol 2 (1991) (3) Atkinson R; J Phys Chem Ref Data 

Monograph 1 p. 166 (1989)] **PEER REVIEWED** 

Environmental Biodegradation: 

ANAEROBIC: Ethyl acetate has been demonstrated to be amenable to anaerobic biodegradation(1). It 

was mineralized (>75% of theoretical methane production) in 10% sludge from a secondary digester 

within 8 weeks(2). 96% utilization occurred in an anaerobic reactor with a 20 day retention time(3). 

Ethyl acetate, at a concentration of 1000 mg/l, was readily degraded in batch reactors containing 

anaerobic solids from an industrial anaerobic digester with some exposure to ethyl acetate(4). 100% 

loss of ethyl acetate was observed in aquifer slurries amended with sulfate and nitrate following 244 

days and 85 days incubation, respectively(5). 94% of theoretical methane production was observed 

after incubation in sediment and groundwater collected from the methanogenic portion of an anoxic 

aquifer polluted by municipal landfill leachate(6). 

[(1) Speece RE; Environ Sci Tech 17: 416A-27A (1983) (2) Shelton DR, Tiedje JM; Appl Environ 

Microbiol 47: 850-7 (1984) (3) Chou WL et al; Biotech Bioeng Symp 8: 391-414 (1979) (4) Schwartz 

LJ; Appl Biochem Biotehcnol 28/29: 297-305 (1991) (5) Mormile MR et al; Environ Sci Technol 28: 

1727-32 (1994) (6) Sulfita JM, Mormile MR; Environ Sci Technol 27: 976-8 (1993)] **PEER 

REVIEWED**

A review concluded that ethyl acetate is easily removed by biological treatment(1). Reported 5 day 

BOD values using a sewage inoculum range from 36-68% of theoretical(2-5) with the value being 

somewhat reduced in salt water(2). One investigator reported that ethyl acetate was completely 

degraded in 20 hr using activated sludge(6). In a bench-scale continuous-flow activated sludge reactor 

with an 8 hour retention time, 99.9% removal (including 17% volatilization loss) was obtained, with 

80% of the theoretical BOD(7). Ethyl acetate was 90% biooxidized in a 20-day BOD test using a 

filtered raw sewage seed; it was biooxidized 77% in a 28-day OECD closed-bottle test(8). A screening 

procedure that was systematically applied to a large number of organic chemicals ranked ethyl 

acetate as being completely biodegraded in a short time by general microorganisms(9). After a 5 hr 

lag, 43 to 53% of theoretical BOD was obtained in 50 to 70 hr(9). In screening tests, ethyl acetate, 

present at a concentration of 5 ppm, reached 26.6 and 57.1% of its theoretical BOD in 5 days using 

the standard dilution method and seawater dilution method, respectively(10). 99.9% removal of ethyl 

acetate was observed in a complete mix continuous-flow activated sludge system; 93% of this 

removal was attributed to biodegradation(11). 

[(1) Thom NS, Agg AR; Proc Roy Soc London B 189: 347-57 (1975) (2) Price KS et al; J Water Pollut 

Control Fed 46: 63-77 (1974) (3) Ettinger MB; Ind Eng Chem 48: 256-9 (1956) (4) Young RHF et al; J 

Water Pollut Control Fed 40: 354-68 (1968) (5) Heukelekian H, Rand MC; J Water Pollut Control 

Assoc 29: 1040-53 (1955) (6) Slave T et al; Rev Chim 25: 666-70 (1974) (7) Stover EL, Kincannon 

DF; J Water Pollut Control Fed 55: 97-109 (1983) (8) Waggy GT et al; Environ Toxicol Chem 13: 

1277-80 (1994) (9) Urano K, Kato Z; J Haz Mat 13: 135-45, 147-59 (1986) (10) Takemoto S et al; 

Suishitsu Odaka Kenkyu 4: 80-90 (1981) (11) Kincannon DF et al; J Water Pollut Control Fed 55: 

157-63 (1983)] **PEER REVIEWED** 

Environmental Abiotic Degradation: The rate constant for the vapor-phase reaction of ethyl acetate 

with photochemically-produced hydroxyl radicals is 1.6X10-12 cu cm/molecule-sec at 25 deg C(1). 

This corresponds to an atmospheric half-life of about 10 days at an atmospheric concentration of 

5X10+5 hydroxyl radicals per cu cm(1,SRC). The observed rate constant for the vapor-phase reaction 

of ethyl acetate with nitrate radicals is 1.4X10-17 cu cm/molecule-sec(2). This corresponds to an 

atmospheric half-life of about 16 years at an average nighttime nitrate radical concentration of 

2X10+8 molecules/cu cm (nitrate radicals are unstable in sunlight)(3,SRC). The rate constant for the 

reaction of ethyl acetate with hydroxyl radicals in aqueous solution is 4.0X10+8 L/mol sec(4). This 

corresponds to a half-life of about 5.5 years(SRC) at an average aqueous hydroxyl radical 

concentration of 1X10-17 mol/l(5). Simple esters are resistant to hydrolysis; ethyl acetate's hydrolysis 

half-life at 25 deg C and pH 7 is 2.0 years(6). 

[(1) Atkinson R; J Phys Chem Ref Data Monograph 1 p. 166 (1989) (2) Atkinson R; J Phys Chem Ref 

Data Monograph p. 213 (1994) (3) GEMS; Graphical Exposure Modeling System. FAP. Fate of Atmos 

Pollut (1986) (4) Buxton GV et al; J Phys Chem Ref Data 17: 513-882 (1988) (5) Mill T et al; Science 

207: 886-7 (1980) (6) Mabey WR et al; J Phys Chem Ref Data Vol 7, No. 2 p. 411 (1978)] **PEER 

REVIEWED** 

Environmental Bioconcentration: An estimated BCF of 3.2 was calculated for ethyl acetate(SRC), 

using a log Kow of 0.73(1) and a regression-derived equation(2). According to a classification 

scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC). 

[(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref 

Book. Heller SR (consult ed) Washington,DC: Amer Chem Soc p. 9 (1995) (2) Lyman WJ et al; 

Handbook of Chemical Property Estimation Methods. Washington DC: Amer Chem Soc pp. 5-4, 5- 

10 (1990) (3) Franke C et al; Chemosphere 29: 1501-14 (1994)] **PEER REVIEWED**

Soil Adsorption/Mobility: The Koc of ethyl acetate is estimated as 59(SRC), using a log Kow of 

0.73(1) and a regression-derived equation(2,SRC). According to a classification scheme(3), this 

estimated Koc value suggests that ethyl acetate is expected to have high mobility in soil(SRC). 

[(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref 

Book. Heller SR (consult ed) Washington,DC: Amer Chem Soc p. 9 (1995) (2) Lyman WJ et al; 

Handbook of Chemical Property Estimation Methods. Washington,DC: Amer Chem Soc pp. 4-9 

(1990) (3) Swann RL et al; Res Rev 85: 23 (1983)] **PEER REVIEWED** 

Volatilization from Water/Soil: The Henry's Law constant for ethyl acetate is 1.34X10-4 atm-cu 

m/mole(1). This Henry's Law constant indicates that ethyl acetate is expected to volatilize from water 

surfaces(2,SRC). Based on this Henry's Law constant, the estimated volatilization half-life from a 

model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec) is estimated as 8.9 hours(2,SRC). 

The estimated volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity 

of 0.5 m/sec) is estimated as 5.6 days(2,SRC). Ethyl acetate's Henry's Law constant(1) indicates that 

volatilization from moist soil surfaces may occur(SRC). The potential for volatilization of ethyl acetate 

from dry soil surfaces may exist(SRC) based on a vapor pressure of 93 mm Hg(3). 7% of the 99.9% 

removal observed in a continuous flow activated sludge system was attributed to stripping(4). 

[(1) Butler JAV, Tamchandani CN; J Chem Soc: 952-5 (1935) (2) Lyman WJ et al; Handbook of 

Chemical Property Estimation Methods. Washington,DC: Amer Chem Soc pp. 15-1 to 15-29 (1990) 

(3) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals: Data 

Compilation. Design Inst Phys Prop Data, Amer Inst Chem Eng., NY,NY: Hemisphere Pub Corp, Vol 2 

(1991) (4) Kincannon DF et al; J Water Pollut Control Fed 55: 157-63 (1983)] **PEER REVIEWED** 

Environmental Water Concentrations: DRINKING WATER: Ethyl acetate was detected, not 

quantified in 3 New Orleans drinking water plants(1). It was detected in drinking water, no levels 

given(2). Ethyl acetate was identified in commercially bottled Artesian water(3). 

[(1) Keith LH et al; pp. 329-73 in Identification and Analysis of Organic Pollutants in Water Keith LH 

ed Ann Arbor Press, Ann Arbor MI (1976) (2) Kool HJ et al; Crit Rev Environ Control 12: 307-57 

(1982) (3) Dowty BJ et al; Environ Sci Technol 9: 762-5 (1975)] **PEER REVIEWED** 

GROUNDWATER: It was not detected in an aquifer polluted by a paint factory even though ethyl 

acetate was stored in buried tanks that leaked(1). 

[(1) Botta D et al; Comm Eur Com Eur 8518 (Anal Org Micropollut Water): 261-75 (1984)] **PEER 

REVIEWED** 

SURFACE WATER: 14 heavily industrialized river basins in USA (204 sites)-only 1 site (Delaware River 

Basin) positive-1 ppb(1). Hayashida River in Tatsumo City, Japan (site of leather industry) 585 ppb(2). 

Ethyl acetate was identified in water samples from the brook, Rickenbach East, Switzerland, which 

receives discharges from a paint factory(3). 

[(1) Ewing BB et al; Monitoring to Detect Previously Unrecognized Pollutants in Surface Waters p. 75 

USEPA-560/6-77-015 (1977) (2) Yasuhara A et al; Environ Sci Technol 15: 570-3 (1981) (3) Juettner 

F; Wat Sci Tech 25: 155-64 (1992)] **PEER REVIEWED** Effluent Concentrations: Effluent gas from 

the metal painting factory and from the lumber painting factory contained ethyl acetate. [Yasuhara A 

et al; Chemosphere 13 (3): 469-82 (1984)] **PEER REVIEWED** 

Ethyl acetate was detected, not quantified in oil refinery final effluent(1) and effluent from sewage 

treatment plants(2). Ethyl acetate has been detected in U.S. municipal landfill leachate at 

concentrations ranging from 42 to 290 g/l(3). Ethyl acetate was identified, but not quantified, in

hazardous waste samples from a Midwest remedial action site(4). Ethyl acetate was detected, but not 

quantified, in a grab sample of oil refinery final effluent from a refinery in Lockport, IL(5). Ethyl 

acetate was identified as a volatile organic compound in a composite waste sample obtained from a 

barge which dumped its waste on Feb 9, 1978 at the Puerto Rico dumpsite(6). Ethyl acetate was 

identified in flue gas from a waste incineration plant in Germany(7). 

[(1) Ellis DD et al; Arch Environ Contam Toxicol 11: 373-82 (1982) (2) Shackelford WM, Keith LH; 

Frequency of Organic Compounds Identified in Water USEPA-600/4-76-062 (1976) (3) Roy WR; 

Contam Groundwaters, Adriano DC et al eds, Sci Rev: Northwood, UK 411-46 (1994) (4) Puskar MA 

et al; Environ Sci Technol 21: 90-6 (1987) (5) Ellis DD et al; Arch Environ Contam Toxicol 11: 373-82 

(1982) (6) Brooks JM et al; Wastes Ocean, Vol 1, Duedall, IW ed, NY,NY: Wiley pp. 171-98 (1983) 

(7) Jay K, Stieglitz L; Chemosphere 30: 1249-60 (1995)] **PEER REVIEWED** 

Atmospheric Concentrations: 

URBAN/SUBURBAN: Ethyl acetate was detected, not quantified in Leningrad, USSR(1). Average 

concentrations of ethyl acetate in urban air samples collected from four different sites in Stockholm 

ranged from 0.27 to 2.64 ppb; the average concentration at a site 12 km outside Stockholm was 0.23 

ppb(2). It was identified in ambient air from Pasadena, TX, Houston, TX, and Glendora, CA(3). 

SOURCE AREAS: It was detected in ambient air surrounding Kin Buc waste disposal site (4 sites) 0, 

trace, 4.1, 230 ug/cu m(4). Ethyl acetate was detected in ambient air near a furnace used for 

incinerating paint wastes at a concentration of 0.7 ppbv(5). 

[(1) Ioffe BV et al; J Chromatogr 142: 787-95 (1977) (2) Jonsson AE et al; Environ Int 11: 383-92 

(1985) (3) Pellizarri ED; Development of Analytical Techniques for Measuring Ambient Atmospheric 

Carcinogenic Vapors, EPA-600/2-75-076 (1975) (4) Pellizarri ED; Environ Sci Technol 16: 781-5 

(1982) (5) Kelly TJ et al; Environ Sci Technol 27: 1146-53 (1993)] **PEER REVIEWED** 

OTHER: 5 out of 8 personal air samples collected from volunteers in Bayonne and Elizabeth, NJ 

between July and Dec 1980 contained ethyl acetate at unreported concentrations(1). Ethyl acetate 

was identified in air at a forest site in the Eggegebirge in North Rhine-Westfalia, West Germany(2). 

INDOOR: Ethyl acetate was detected in air samples taken from preschools in Stockholm(3). Ethyl 

acetate was detected in indoor air samples from Northern Italy at concentrations of 9 and 26 ug/cu 

m(4). It was detected in indoor air collected in a machine shop and a new office area at 

concentrations of 1.4 and 21.8 ppbv, respectively(5). Ethyl acetate was detected in the indoor air of 

12 out of 12 Canadian homes in Nov and Dec 1986 at concentrations ranging from 3 to 13 ug/cu m, 

average 8.9 ug/cu m; indoor air concentrations in 6 Canadian homes in Feb and March 1987 ranged 

from 7 to 494 ug/cu m, average 153 ug/cu m (outdoor air average concentration 10 ug/cu m)(6). Ethyl 

acetate was detected in indoor air of new and recently renovated buildings in Switzerland at a 

maximum concentration of 1052 ug/cu m(7). It was detected in at least one indoor air sample from 

17 locations from two Stockholm preschools(8). 

[(1) Wallace LA et al; Environ Res 35: 293-319 (1984) (2) Helmig D et al; Chemosphere 19: 1399- 

1412 (1989) (3) Noma E et al; Atmos Environ 22: 451-60 (1988) (4) DeBortoli M et al; Environ Int 

12: 343-50 (1986) (5) Kelly TJ et al; Environ Sci Technol 27: 1146-53 (1993) (6) Chan CC et al; J Air 

Waste Manage Assoc 40: 62-7 (1990) (7) Rothweiler H et al; Atmos Environ 26A: 2219-25 (1992) (8) 

Noma E et al; Aimos Environ 22: 451-60 (1988)] **PEER REVIEWED**

Food Survey Values: Ethyl acetate forms from the reaction of acetyl coenzyme A with ethanol, and its 

formation depends greatly on temperature. Maximum formation occurs at 20-25 deg C. Therefore, 

top fermented beers contain higher amounts of this ester. 

[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John 

Wiley and Sons, 1978-1984., p. V24 789 (1984)] **PEER REVIEWED** 

Ethyl acetate is found in USA lager beer, 25 to 50 ppm(1). It is a component of Orleans vinegar(2) 

and artificial grape flavoring(3). Ethyl acetate was identified as a volatile component of roasted 

filberts(4), fried bacon(5), Beaufort cheese(6), blue cheese(7), Idaho Russet Burbank baked 

potatoes(8), and the edible Korean chamchwi plant(9). Korean salt-fermented anchovy, big-eyed 

herring, hair tail viscera and shrimp pastes contained ethyl acetate at mean concentrations of 3490, 

1660, 2340, and 3750 ng/g, respectively(10). Ethyl acetate was detected in beer at a concentration of 

8 ppm(11). Ethyl acetate was identified as a volatile compound in kiwi fruit, comprising 3.9, 4.7, and 

1.6% of the components in mature, ripe, and very ripe fruit, respectively(12). It was also identified as 

a volatile component of pineapple guava at a concentration of 0.11 ug/g(13). Fresh grapefruit juice 

contained 1.65 ppm ethyl acetate(14). Ethyl acetate was identified in mature and overripe guava 

fruits at concentrations of 614.1 and 8884.2 ug/kg, respectively(15). It was identified as a volatile 

flavor component of the strawberry variety Sivetta and in Golden Delicious apples(16). 

[(1) Reed G; Kirk-Othmer Encycl Chem Tech 3rd ed. NY,NY: Wiley Interscience 24: 789 (1983) (2) 

Webb AD; Kirk-Othmer Encycl Chem Tech 3rd ed. NY,NY: Wiley Interscience 23: 757 (1983) (3) 

Jones MB; Kirk-Othmer Encycl Chem Tech 3rd ed. NY,NY: Wiley Interscience 4: 712 (1978) (4) 

Kinlin TE et al; J Agric Food Chem 20: 1021-8 (1972) (5) Ho CT et al; J Agric Food Chem 31: 336-42 

(1983) (6) Dumont JP, Adda J; J Agric Food Chem 26: 364-7 (1978) (7) Day EA, Anderson DF; J Agric 

Food Chem 13: 2-4 (1965) (8) Coleman EC et al; J Agric Food Chem 29: 42-8 (1981) (9) Chung TY et 

al; J Agric Food Chem 41: 1693-7 (1993) (10) Cha YJ, Cadwallader KR; J Food Sci 60: 19-24 (1995) 

(11) Hashimoto H, Kuroiwa YJ; J Inst Brewing 72: 151-62 (1966) (12) Bartley JP, Schwede AM; J Agric 

Food Chem 37: 1023-5 (1989) (13) Binder RG, Flath RA; J Agric Food Chem 37: 734-6 (1989) (14) 

Cadwallader KR, Xu Y; J Agric Food Chem 42: 782-4 (1994) (15) Chyau CC et al; J Agric Food Chem 

40: 846-9 (1992) (16) Dirinck P et al; Analysis of Volatiles, Berlin,Germany: Walter Degruyter and Co 

381-400 (1984)] **PEER REVIEWED** 

Ethyl acetate was identified as a volatile component of duck meat, duck fat, Cantonese style roasted 

duck, and Cantonese style roasted duck gravy at concentrations of

MG, Shaw PE; J Agric Food Chem 42: 1525-8 (1994) (10) Mattheis JP et al; J Agric Food Chem 39: 

1902-6 (1991)] **PEER REVIEWED** 

Plant Concentrations: Ethyl acetate was identified as a volatile component of kiwi fruit flowers(1). 

Volatile emissions from Scots pine were found to contain ethyl acetate(2). 

[(1) Tatsuka K et al; J Agric Food Chem 38: 2176-80 (1990) (2) Singh HB, Zimmerman PB; Adv 

Environ Sci Technol 24: 177-235 (1992)] **PEER REVIEWED** 

Fish/Seafood Concentrations: Ethyl acetate was identified in a sample of mussel collected from the 

Oarai Coast in Ibaraki, Japan on July 31, 1985 at a concentration of 97.1 ug/g(1). 

[(1) Yashuara A, Morita M; Chemosphere 16: 2559-65 (1987)] **PEER REVIEWED** 

Milk Concentrations: Mother's milk from 4 urban areas in the USA, 1 of 8 samples positive(1). 

[(1) Pellizarri ED et al; Environ Sci Technol 16: 781-5 (1982)] **PEER REVIEWED** 

Other Environmental Concentrations: Nail polish remover typically contains 40 wt% ethyl 

acetate(1,2). Ethyl acetate was identified as a volatile component in fresh and used machine cuttingfluid 

emulsions at concentrations of 0.171 and 0.310 ug/g, respectively(3). Ethyl acetate was 

identified in the headspace of biodegradable and mixed household waste at concentrations ranging 

from 0.1 to 1 mg/cu m(4). It was also identified in liquid exudate from garden waste(5). Ethyl acetate 

has been identified as a volatile compound in the headspace of kitchen waste and mold-infested fiber 

board, kitchen waste exudate, stored food exudate, and garden waste headspace(6). Ethyl acetate 

was identified in 8 printer's inks at concentrations ranging from 0.1 to 13.7% (w/w)(7). Ethyl acetate 

was identified in volatile emissions from Scots pine(8). Ethyl acetate comprised 2.0 and 3.7% by 

weight of total organic gas emissions from industrial surface coatings and thinning solvent, 

respectively(9). Mean emission rates of ethyl acetate from particle board/carpet were 0.025 mg/sq m 

hr(10). Ethyl acetate emissions from whiskey vats averaged 0.593 g/cu m grain input(11). Ethyl acetate 

was found in glue used in Italian shoe factories(12). Ethyl acetate was identified as a volatile organic 

compound present in 3 of 3 samples of poultry manure at concentrations of 10.8, 23.0, and 61.2 

mg/kg(13). 

[(1) Isacoff H; Kirk-Othmer Encycl Chem Tech; 3rd ed. NY,NY: Wiley Interscience 7: 163 (1979) (2) 

Wallace LA et al; Res Triangle Inst, Research Triangle Park, NC Report 1991, USEPA/600/D-91/074; 

(NTIS PB-91-182865) (1991) (3) Yasuhara A et al; Agric Biol Chem 50: 1765-70 (1965) (4) Wilkins K; 

Chemosphere 29: 47-53 (1994) (5) Wilkins K, Larsen K; Chemosphere 32: 2049-55 (1996) (6) 

Wilkins CK, Larsen K; J High Resol Chromatogr 18: 373-7 (1995) (7) Rastogi SC; Arch Environ 

Contam Toxicol 20: 543-7 (1991) (8) Isidorov VA et al; Atmos Environ 19: 1-8 (1985) (9) Harley RA 

et al; Environ Sci Technol 26: 2395-408 (1992) (10) Colombo A et al; Sci Total Environ 91: 237-49 

(1990) (11) Carter RV, Linsky B; Atmos Environ 8: 57-62 (1974) (12) Perbellini L et al; Med Lav 83: 

115-19 (1992) (13) Yashuara A; J Chromatogr 387: 371-8 (1987)] **PEER REVIEWED** 

As taken from HSDB powered by Toxnet, 2010 available at http://toxnet.nlm.nih.gov/cgibin/sis/htmlgen?HSDB

9.2 Aquatic toxicity 

Ecotoxicity Values: 

LC50 HETEROPNEUSTES FOSSILIS (COMMON INDIAN CATFISH) 212.5 PPM/96 HR 

/CONDITIONS OF BIOASSAY NOT SPECIFIED/ 

[GUPTA AB, SRIVASTAVA AK; ECOTOXICOL ENVIRON SAF 6 (2): 166-70 (1982)] **PEER 

REVIEWED** 

LC50 Pimephales promelas (fathead minnow) 230 mg/l/96 hr (confidence limit 220-250 mg/l). 

Contamination of chemical in the control tanks - possibly due to volatility of the cmpd. /Conditions of 

bioassay not specified/ 

[Brooke, L.T., D.J. Call, D.T. Geiger and C.E. Northcott (eds.). Acute Toxicities of Organic Chemicals 

to Fathead Minnows (Pimephales Promelas). Superior, WI: Center for Lake Superior Environmental 

Studies Univ. of Wisconsin Superior, 1984., p. 103] **PEER REVIEWED** 

EC50 Pimephales promelas (fathead minnow) 220 mg/l/96 hr (confidence limit 210-240 mg/l). 

Contamination of chemical in the control tanks - possibly due to volatility of the cmpd. Affected fish 

lost equilibrium prior to death. /Conditions of bioassay not specified/ 

[Brooke, L.T., D.J. Call, D.T. Geiger and C.E. Northcott (eds.). Acute Toxicities of Organic Chemicals 

to Fathead Minnows (Pimephales Promelas). Superior, WI: Center for Lake Superior Environmental 

Studies Univ. of Wisconsin Superior, 1984., p. 103] **PEER REVIEWED** 

Acute/Prolonged Toxicity to Fish 

Type: flow through 

Species: Leuciscus idus melanotus (Fish, fresh water) 

Exposure period: 48 hour(s) 

Unit: mg/l 

LC0: = 135 – 306 

LC50: = 270 – 333 

LC100: = 360 – 360 

Method: other: DIN 384 12 L–20 

Year: 1978 

Source: NEUBER GES.M.B.H. WIEN(78) 

Type: flow through

Species: Oncorhynchus mykiss (Fish, fresh water) 


Unit: mg/l 

LC50: 484 

Year: 1986 



Species: Pimephales promelas (Fish, fresh water) 


Unit: mg/l 

Analytical monitoring: yes 

LC50: = 230 

Method: other: Acute Toxicity Tes 

other TS: > 99 % pure 

Remark: 29 – 30 d old fish 


Test condition: 24.3 degree C; pH 7.4; 6.7 mg O2/l; hardness: 45.0 mg/l as CaCO3 




Unit: mg/l 

LC50: 230 

Year: 1984 

Source: Petrasol B.V. Gorinchem(2)

Type: semistatic 

Species: Salmo gairdneri (Fish, estuary, fresh water) 


Unit: mg/l Analytical monitoring: no data 

LC50: 454.7 

Method: OECD Guide–line 203 "Fish, Acute Toxicity Test" 

Year: 1981 GLP: no dataTest substance: no data 

Remark: 

in difference to the OECD–Guide–line 203: 7 fish/group, 4 concentration groups 


Type: static 

Species: Leuciscus idus (Fish, fresh water) 


Unit: mg/l Analytical monitoring: no 

LC0: = 300 

LC50: = 350 

Method: other: Bestimmung der Wirkung von Wasserinhaltsstoffen auf Fische, DIN38412 Teil 

15 

Test substance: other TS: refer to Huels Section 1 dossier. 


Type: static 


Exposure period: 48 hour(s)


LC0: = 135 

LC50: = 270 

LC100: = 360 


15; draft proposal 

Year: 1976 

GLP: no data 



Type: static 




LC0: = 306 

LC50: = 333 

LC100: = 360 


15; draft proposal 

Year: 1976 

GLP: no data 


Source: BP Chemicals Ltd. London (81)

Type: static 

Species: Oryzias latipes (Fish, fresh water) 



LC50: = 900 

Method: other: Acute Toxicity Test 

Remark: 

LC50 at 10 degree C = 1500 mg/l 

LC50 at 30 degree C = 1500 mg/l; 

maximum concentration for survival of all fish: 

268 mg/l (48–h incubation; 30 degree C) 


Test condition: 20 degree C 

Type: static 

Species: Oryzias latipes (Fish, fresh water) 



LC50: = 125 

NOLC : = 100 

Method: other: Acute Toxicity Text 


Remark: NOLC: highest test concentration at which no lethality was observed; 4 – 5–week old 

fish


Test condition: 24 degree C; Dutch Standard Water according to Canton and Slooff (1982) 

Type: static 




LC50: = 270 

NOLC : = 180 




fish 


Test condition: 20 degree C; Dutch Standard Water according to Canton and Slooff (1982) 

Type: static 

Species: Poecilia reticulata (Fish, fresh water) 



LC50: = 210 

NOLC : = 160 




fish

Source: BP Chemicals Ltd. London (84) (83) 

Test condition: 24 degree C; test medium according to Alabaster and Abraham (1965; "hard water") 

Type: static 




LC50: = 260 

NOLC : = 240 




fish 


Test condition: 15 degree C; tap water (pH 7 – 8) 

Type: static 

Species: other: Heteropneustes fossilis (Fish, fresh water) 



LC0: = 80 

LC50: = 212.5 

LC100: = 350 

Method: other: Acute Toxicity Test according to Standard Methods for theExamination of 

Water and Wastewater, APHA 

Year: 1971 

other TS: vehicle: absolute alcohol


Test condition: 17.6 +– 0.28 degree C; pH 7.4 +– 0.03; dissolved oxygen 6.37 +– 0.14 mg/l; 

hardness: 108 +– 6.96 mg/l as CaCO3 




LC50: 230 


Remark: no further information available 

Source: BP Chemicals Ltd. London86) 

Acute Toxicity to Aquatic Invertebrates 

( 

Species: Artemia salina (Crustacea) 



EC50: = 644.8 

Method: other: Acute Immobilization Test 

other TS: > 98 % pure; vehicle: acetone 

Remark: Artemisia nauplii were tested in 50 % artificial see water; EC50 in 25 % artificial 

seawater: 345.9 mg/l 


Test condition: 19 degree C; pH 8.3 – 8.6; 7.3 – 8.7 mg dissolved oxygen/l (87) 

Species: Artemia salina (Crustacea)


Unit: mg/l 

Analytical monitoring: no data 

EC50: = 1590 


Test condition: 24.5 degree C 

Species: Daphnia cucullata (Crustacea) 



EC50: = 164 

Method: other: Acute Toxicity Test according to the concept rules of the DutchStandardization 

Institute 

other TS: purest grade 

Remark: 11 +– 1 d old organisms 


Species: Daphnia magna (Crustacea) 

Unit: mg/l 

EC50: = 590 




Unit: mg/l Analytical monitoring: no

EC50: = 717 


Institute 

Remark: 11 +– 1 d old organisms; 

EC50: average of tests conducted in two laboratories 




Unit: mg/l 

EC50: > 1000 

Method: other: Daphnien–Kurzzeittest, DIN 38412 Teil 11, Bestimmung der Wirkungvon 

Wasserinhaltsstoffen auf Kleinkrebse 

Year: 1982 GLP: no 

Test substance: other TS: refer to Huls Section 1 dossier. 




Unit: mg/l 

EC0: = 625 

EC50: = 2500 

EC100: = 5000 

Method: other: Immobilization Test 


Test condition: 20 – 22 degree C; open test system




EC0: = 1562 

EC50: = 3090 

EC100: = 6000 

Method: other: Immobilization Test 


Test condition: 20 degree C; artificial fresh water (German DIN 38412 Teil 11, draft proposal); open 

test system 



Unit: mg/l 

EC0: = 625 

EC50: = 2500 

EC100: = 5000 

Year: 1977 

Source: NEUBER GES.M.B.H. WIEN (92) 



Unit: mg/l 

EC50: 2306 

Year: 1988


Species: Daphnia pulex (Crustacea) 


Unit: mg/l 

EC50: = 262 


Institute 

Remark: 11 +– 1 d old organisms 


Species: Daphnia pulex (Crustacea) 


Unit: mg/l 

LC50 : 295 

Year: 1978 


Species: Gammarus pulex (Crustacea) 


Unit: mg/l 

LC50 : = 750 


Test substance: other TS: > 98 % pure 

Remark: Mortalities were recorded at a 24–h time interval.


Test condition: 20 +– 1 degree C; Dutch Standard Water (93) 

Species: other aquatic mollusc: Lymnea stagnalis 



LC50 : = 1100 


Remark: Mortalities were recorded at a 24–h time interval; highest concentration at which no 

lethality was observed (NOLC) = 560 mg/l. 


Test condition: 20 +– 1 degree C; Dutch Standard Water (93) (83) 

Species: other aquatic worm: Dugesia cf. lugubris (Plathelminthes) 



LC50 : = 3020 



Remark: Mortalities were recorded at a 24–h time interval. 



Species: other aquatic worm: Erpobdella octoculata (Hirudinea) 


Unit: mg/l Analytical monitoring: no data

LC50 : = 1200 






Species: other aquatic crustacea: Asellus aquaticus 



LC50 : = 1600 






Toxicity to Aquatic Plants e.g. Algae 

Species: Chlorella pyrenoidosa (Algae) 

Endpoint: biomass 



NOEC: > 1000 



Test condition: 25 degree C(83)

Species: Microcystis aeruginosa (Algae, blue, cyanobacteria) 


Exposure period: 8 day 


TT : = 550 

Method: other: Cell Multiplication Inhibition Test 

Year: 1976 

Remark: TT = toxicity threshold 


Test condition: 27 degree C; pH 7.0(94) (95) 

Species: Scenedesmus pannonicus (Algae) 




NOEC: > 1000 




Test condition: 25 degree C(83) 

Species: Scenedesmus quadricauda (Algae) 




TT : = 15 




Test condition: 27 degree C; pH 7.0(96) (97) 

Species: Scenedesmus quadricauda (Algae) 

Endpoint: growth rate 



EC0: = 15 

Method: other: nicht bekannt 

Year: 1978 GLP: no dataTest substance: no data 

Source: NEUBER GES.M.B.H. WIEN(98) 

Species: Scenedesmus subspicatus (Algae) 




EC10: = 1600 

EC50: = 3300 

Method: other: Cell Multiplication Inhibition Test according to German DIN38412, part 9 

(draft standard) 

Year: 1988 

Remark: Concentration of the ethyl acetate stock solution was determined analytically 

preceding to the dilution steps; EC values were expressed as the arithmetically 

calculated concentrations of the dilution steps.





Unit: mg/l 

EC50: 3300 

Year: 1990 





Unit: mg/l 

EC10: = 2300 

EC50: = 5600 

Method: other: Cell Multiplication Inhibition Test according to German DIN38412, part 9 

(draft standard) 

Year: 1988 

Remark: Concentration of the ethyl acetate stock solution was determined analytically 

preceding to the dilution steps; EC values were expressed as the arithmetically 

calculated concentrations of the dilution steps. 




Exposure period: 72 hour(s)


NOEC: > 100 

Method: other: Directive 88/302/EEC, part C, p. 89 

Year: 1988 GLP: yes 

Test substance: other TS: refer to Huls Section 1 dossier 

Remark: Hoehere Konzentrationen sind aufgrund zeitweise auftretender Eigentruebungen in 

einigen Parallelen der beimpften Testansaetze nicht auswertbar. 

Source: BP Chemicals Ltd. London100) 

( 




Unit: mg/l 

EC50: 5600 

Year: 1990 


Species: Selenastrum capricornutum (Algae) 




NOEC: = 2000 




Test condition: 26 degree C

Toxicity to Microorganisms e.g. Bacteria 

Type: aquatic 

Species: Chilomonas paramaecium (Protozoa) 



TT : = 3248 




Test condition: 20 degree C; pH 6.9; axenic culture 

Type: aquatic 

Species: Entosiphon sulcatum (Protozoa) 



TT : = 202 




Test condition: 25 degree C; pH 6.9 

Type: aquatic 

Species: Photobacterium phosphoreum (Bacteria) 

Exposure period: 15 minute(s) 


EC10: = 1650 

EC50: = 5870 

Method: other: Microtox Assay System 

Year: 1979 GLP: no dataTest substance: 


Remark: 5–min EC50 = 5160 mg/l; 5–min EC10 = 930 mg/l 


Test condition: 15 +– 0.1 degree C 

Type: aquatic 

Species: Photobacterium phosphoreum (Bacteria) 



EC50: = 1180 

Method: other: Microtox Bioluminescence Assay 


Type: aquatic 

Species: Pseudomonas fluorescens (Bacteria) 



EC50: = 7400 

other: Growth Rate Inhibition Test 


Test condition: 33 degree C

Type: aquatic 

Species: Pseudomonas fluorescens (Bacteria) 



EC50: = 1500 

Method: other: Microtox Assay System 

Year: 1984 


Type: aquatic 

Species: Pseudomonas putida (Bacteria) 



TT : = 650 

other: Cell Multiplication Inhibition Test 




Type: aquatic 



Unit: mg/l 

EC10: = 2900 

Method: other: Pseudomonas–Zellvermehrungs–Hemmtest, DIN 38412 Teil 8, draftproposal, 

Bestimmung der Hemmwirkung von Wasserinhaltsstoffen aufBakterien

other TS: refer to Huls Section 1 dossier. 


Type: aquatic 




EC0: = 650 

Method: other: nicht bekannt 

Year: 1980 

Source: NEUBER GES.M.B.H. WIEN (107) 

Type: aquatic 

Species: Uronema parduzci (Protozoa) 



TT : = 1620 

other: Cell Multiplication Inhibition Test 

Year: 1978 




Chronic Toxicity to Aquatic Organisms 

Chronic Toxicity to Fish 

Species: Pimephales promelas (Fish, fresh water)

Endpoint: weight of young fish 



LOEC: = 9.65 

Method: other: Embryo–Larval Test 

Remark: LOEC refers to the lowest concentration tested. Growth inhibition was lower at all 

higher concentrations tested (19.40, 30.08, 49.40, 75.60 mg/l). 


Test condition: soft Lake Superior Water(110) 

Chronic Toxicity to Aquatic Invertebrates 

Species: Daphnia sp. (Crustacea) 

Endpoint: mortality 


Unit: mg/l 

Death : 1.5 



Endpoint: reproduction rate 


Unit: µg/l 

LD100 : 2400 

Year: 1989 



9.3 Sediment toxicity 

No data available to us at this time. 

9.4 Terrestrial toxicity 

TERRESTRIAL ORGANISMS 

Toxicity to Soil Dwelling Organisms 

Species: other: sediment dwelling worm: Tubifex and Limnodrilus 



Unit: other: mg/l 

LC50: = 760 

(Tubificidae,Annelida) 





Test condition: 20 +– 1 degree C; Dutch Standard Water 

Toxicity to Terrestrial Plants 

Species: other terrestrial plant: Picea sitchensis (Conifer) 

Endpoint: other: dry weight and photosynthetic CO2 uptake 

Unit: mg/l 

NOEC: ca. 10 

Method: other: Repeated Vapour Exposure Toxicity Test 

Remark: Only dry weight of current stem was decreased significantly at 40 mg/l (60 % of 

control; p


Test condition: Seedlings were flushed with 10 and 40 mg ethyl acetate/l air at a rate of 4 l/min, resp. 

for 15 min/d followed by treatment with normal air (15 – 30 min); exposure period: 

14 d. 

Species: other terrestrial plant: Beta vulgaris (Dicotyledonous) 

Endpoint: other: dry weight and photosynthetic CO2 uptake 

Method: other: Repeated Vapour Exposure Toxicity Test 

Remark: 

Significant dry weight reduction at 10 mg/l and 40 mg/l, 

resp. (p

Remark: 

Total dry weight was reduced significantly (56 % of 

control), as were dry weights of roots and petioles(p

Test condition: 22 – 24 degree C 

Species: other not soil dwelling arthropod: Culex pipiens (Insect) 


Expos. period: 48 hour(s) 


LC50: = 3950 

NOLC : = 2400 




NOLC = highest concentration at which no lethality was observed. 


Test condition: 26 degree C; Dutch Standard Water (according to Canton and Slooff, 1982) 

Species: other not soil dwelling arthropod: Aedes aegypti (Insect) 




LC50: = 350 

NOLC : = 160 



Remark: NOLC: highest test concentration at which no lethality was observed 


Test condition: 26 degree C; Dutch Standard Water (according to Canton and Slooff, 1982)

Species: other not soil dwelling arthropod: Ischnura elegans (Insect) 




LC50: = 600 





Test condition: 20 +– 1 degree C; Dutch Standard Water (according to Canton and Slooff, 1982) 

Species: other not soil dwelling arthropod: Nemoura cinerea (Insect) 




LC50: = 130 






Species: other not soil dwelling arthropod: Cloeon dipterum (Insect)




LC50: = 480 






Species: other not soil dwelling arthropod: Corixa punctata (Insect) 




LC50: = 600 






Species: other not soil dwelling arthropod: Chironomus gr. thummi (Insect) 



Unit: other: mg/l

LC50: = 760 







9.5 All other relevant types of ecotoxicity 

Remark: Narcotic threshold concentration for tadpoles (Rana 

pipiens): 3172 mg/l (concentration at which touching the 

tadpoles failed to cause motion). 


Remark: 

Acute toxicity to Xenopus laevis (Amphibian): 

48–h LC50 = 180 mg/l; 

highest concentration at which no lethality was observed: 

100 mg/l; 

GLP: no data; 

Analyt. Monitoring: no data; 

20 +– 1 degree C; 

testmedium: Dutch Standard Water; 

10 animals/concentration were tested 3 – 4 weeks after 

hatching. 


Test substance: ethyl acetate dissolved in distilled water

Remark: 

Acute toxicity to Ambystoma mexicanum (Amphibian): 

48–h LC50 = 150 mg/l; 


100 mg/l; 

GLP: no data; 


20 +– 1 degree C; 

testmedium: Dutch Standard Water; 

10 animals/concentration were tested 3 – 4 weeks after 

hatching. 


Test substance: ethyl acetate dissolved in distilled water 

Remark: 

Acute toxicity for Hydra oligactis (Hydrozoa): 

48–h LC50 = 1350 mg/l; 


1120 mg/l; 

GLP: no data; 


17 degree C; 

test medium: Dutch Standard Water. 

Source: BP Chemicals Ltd. London(93) (83)

Remark: 

Exposure of Heteropneustes fossilis (Fish, fresh water) 

to 170 mg ethyl acetate/l (= 80 % 96–h LC50): 

liver glycogen was decreased significantly after 3, 48 

and 96 h of exposure (p < 0.01); 

blood glucose was increased significantly after 3 and 6 h 

(p < 0.02), 12 and 48 h (p < 0.01) and 96 h (p < 0.001); 

blood pyruvate was increased significantly after 3 and 

48 h (p < 0.01), 6 and 96 h (p < 0.001); 

blood lactate was increased significantly after 3 h (p < 

0.01) and 6, 12, and 96 h (p < 0.001). 


Test substance: vehicle: absolute alcohol 

Remark: 

Unscheduled DNA synthesis in pollen of Petunia hybrida 

(Dicotyldonos) 

Pretreatment of pollen with ethyl acetate completely 

inhibited the 4NQO (4–nitroquinoline–1–oxide)–induced 

unscheduled DNA synthesis in the pollen; 

pretreatment: 35 mg of pollen were incubated 3 times with 

5 ml ethyl acetate at 0 degree C for a total of 15 min; 

germination in the presence of 0.05 M 4NQO for 2 h at 25 

degree C. 


Remark: 

Vicia faba root tip chromosome aberration test Ethyl acetate dose–relatedly decreased 

the number of total anaphases in Vicia faba cells, the frequencies of abnormal 

anaphases and total aberrations were increased, the frequency of C–mitosis was 

increased dose–relatedly, the mitotic index was nearly doubled at 0.5 % ethyl acetate 

(v/v or w/v?) compared to the untreated control, but then declined with increasing 

concentration to one half of the control at 2.5 % ethyl acetate; 1 – 3 h of exposure or 

4 h with recovery in tap water; incubation at 19 degree C in the dark.


Remark: 

In vitro incubation of partially purified Vibrio fischeri 

luciferase with 1180 mg ethyl acetate/l slightly stimulated 

luminescence: 

110 +– 15 % of control at 15 seconds, 

103 +– 7 % at 5 min, 100 +– 22 % at 15 min. 


Remark: 

In vitro incubation of a partially purified firefly 

luceferin–luciferase mxture with 1180 mg ethyl acethyl/l 

slightly decreased luminescence: 

78 +– 2 % of control at 15 seconds, 

100 +– 1 % at 5 min, 87 +– 3 % at 15 min. 



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Evaluation of potential toxic and addictive properties of Ethyl acetate

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