PRINCIPLES OF TOXICOLOGY

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TABLE 16.2 Occupational Exposure Limits for Selected Solvents and Related Materials Compound CAS No. 1999 ACGIH TLV a (ppm) 1999 ACGIH STEL b (ppm) 1999 ACGIH Carcinogen Class 1999 OSHA- PEL (ppm) 1999 OSHA- STEL (ppm) 1999 USEPA Carcinogen Class d Acetaldehyde 75-07-0 NE 25 A3 200 NE B2 Acetone 67-64-1 500 750 A4 1,000 NE D Acrolein 107-02-8 0.1 0.23 A4 0.1 NE C Aniline 62-53-3 2 NE A3 5 NE B2 Benzene 71-43-2 0.5 2.5 A1 1 5 A Benzidine 92-87-5 NE NE A1 NE NE A Carbon disulfide 75-15-0 10 NE NE 20 30 ND Carbon tetrachloride 56-23-5 5 10 A2 10 25 B2 Chloroform 67-66-3 10 NE A3 NE 50 B2 Dimethylaniline 121-69-7 5 10 A4 5 NE ND 1,4-Dioxane 123-91-1 20 NE A3 100 NE B2 Ethanol 64-17-5 1,000 NE A4 1,000 NE ND Ethyl acetate 141-78-6 400 NE NE 400 NE ND Ethyl ether 60-29-7 400 500 NE 400 NE ND Ethylene glycol, aerosol 107-21-1 NE 100 A4 NE NE ND Formaldehyde 50-00-0 NE 0.3 A2 0.75 2 B1 n-Hexane 110-54-3 50 NE NE 500 NE ND Hexane isomers (other) ND 500 1,000 NE NE NE ND Hydrazine 302-01-2 0.01 NE A3 1 NE B2 Isopropanol 67-63-0 400 c 500 A4 400 NE ND Isopropyl ether 108-20-3 250 310 NE 500 NE ND Methanol 67-56-1 200 250 NE 200 NE ND Methyl bromide 74-83-9 1 NE NE NE 20 D Methyl chloride 74-87-3 50 100 A4 100 200 ND Methylene chloride 75-09-2 50 NE A3 25 125 B2 Methyl ethyl ketone 78-93-3 200 300 NE 200 NE D Naphthalene 91-20-3 10 15 A4 10 NE C Nitrobenzene 98-95-3 1 NE A3 1 NE D Nitromethane 75-52-5 20 NE NE c 100 NE ND Phenol 108-95-2 5 NE A4 5 NE D Pyridine 110-86-1 5 NE NE 5 NE ND Styrene 100-42-5 20 40 A4 100 200 ND Tetrahydrofuran 109-99-9 200 250 NE 200 NE ND Toluene 108-88-3 50 NE A4 200 300 D Trichloroethene 79-01-6 50 100 A5 100 200 ND Vinyl chloride 75-01-4 1 NE A1 1 5 A NE Not Established ND No Data, or not classified with regard to carcinogen status by U.S. EPA. a ACGIH Time-Weighted Average Threshold Limit Value (TWA-TLV). b ACGIH Short Term Exposure Limit (STEL) or Ceiling Value. c Changes are pending. d U.S. EPA Carcinogen Classification system presently undergoing reveiw. 16.2 BASIC <strong>PRINCIPLES</strong> 371
372 PROPERTIES AND EFFECTS <strong>OF</strong> ORGANIC SOLVENTS TABLE 16.3 Occupational Exposure Guideline Definitions ACGIH: American Conference of Governmental Industrial Hygienists TLV-TWA: threshold limit value—time-weighted average—time-weighted average concentration for a normal 8-h workday and a 40-h workweek, to which nearly all workers may be repeatedly exposed, day after day, without adverse effects STEL: short-term exposure limit—defined as 15 min TWA exposure that should not be exceeded during a workday; concentration to which workers can be exposed continuously for a short period without suffering irritation, chronic or irreversible tissue damage, or narcosis sufficient to increase likelihood of injury, impair self-rescue or materially reduce work efficiency, provided the TLV-TWA is not exceeded Categories for carcinogenic potential: A1 Confirmed Human Carcinogen A2 Suspected Human Carcinogen A3 Animal Carcinogen A4 Not Classifiable as a Human Carcinogen A5 Not Suspected as a Human Carcinogen OSHA: Occupational Safety and Health Administration PEL-TWA: permissible exposure limit–time-weighted average—concentration not to be exceeded during any 8-h workshift of a 40-h workweek C: ceiling limit—ceiling concentrations must not be exceeded during any part of the workday; if instantaneous monitoring is not feasible, the ceiling must be assessed as a 15-min TWA exposure USEPA Integrated Risk Information System (IRIS database) Categories for carcinogenic potential: A Known Human Carcinogen B1 Probable Human Carcinogen (based on human data) B2 Probable Human Carcinogen (based on animal data) C Possible Human Carcinogen D Not Classifiable as to Human Carcinogenicity (based on lack of data concerning carcinogenicity in humans or animals) have direct applicability in industrial settings. They can be acquired directly from USEPA on databases such as the Integrated Risk Information System (IRIS). Absorption, Distribution, and Excretion Most commonly, due to the characteristic of volatility, solvent exposure occurs via the inhalation route, but there also may be absorption through the skin following exposures to vapors or through direct contact with the liquid form. While penetration of solvent vapors through the skin typically is considered to be negligible at low air concentrations, ACGIH and OSHA specifically note for a number of substances that this route may be significant, hence the “skin” designation in occupational guidelines. This is particularly true in cases where high concentrations exist in confined spaces and where respiratory protection (e.g., use of air-purifying or air-supplied respirators) limits the potential for inhalation exposure. As an example, it has been demonstrated that exposure to vapor of 2-butoxyethanol, a glycol ether, under some conditions may result in uptake through the skin which exceeds uptake via inhalation. Characteristic of all volatile materials, the quantity of solvent that is absorbed by the lungs is dependent on several factors, including pulmonary ventilation rate, depth of respirations, and pulmonary circulation rate, all of which are influenced by workload. The partition coefficients that are representative of solvent behavior in various tissues (i.e., for air:blood, fat:blood, brain:blood) are specific to the chemical structure and properties of the individual solvent. Toluene, styrene, and acetone are examples of rapidly absorbed solvents.
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PRINCIPLES OF TOXICOLOGY
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This book is printed on acid-free p
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vi CONTRI BUTORS PAUL J. MIDDENDORF
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viii CONTENTS 4 Hematotoxicity: Che
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x CONTENTS 12 Mutagenesis and Genet
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xii CONTENTS III APPLICATIONS 435 1
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PREFACE Purpose of This Book Princi
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ACKNOWLEDGMENTS A text of this unde
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PART I Conceptual Aspects Principle
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4 GENERAL PRINCIPLES OF TOXICOLOGY
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36 ABSORPTION, DISTRIBUTION, AND EL
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3 Biotransformation: A Balance betw
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BIOTRANSFORMATION: A BALANCE BETWEE
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BIOTRANSFORMATION: A BALANCE BETWEE
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Figure 3.5 Diagrammatic rendition o
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3.2 BIOTRANSFORMATION REACTIONS The
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TABLE 3.4 Important Cytochrome P450
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Figure 3.8 Cytochrome P450-catalyze
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oth of which are suitable for conju
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TABLE 3.6 Changes in Rat Hepatic Dr
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3.2 BIOTRANSFORMATION REACTIONS 75
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TABLE 3.7 Induction of Xenobiotic-M
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3.2 BIOTRANSFORMATION REACTIONS 79
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pyridoxal phosphate depletion by th
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Biotransformation: A Balance betwee
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een shown to be responsible for the
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4 Hematotoxicity: Chemically Induce
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Figure 4.1 Formation of blood. Matu
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TABLE 4.2 Leukemias and Lymphomas 4
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4.3 THE MYELOID SERIES 93 to contra
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function and response to stimuli, (
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Hypoxia can result from a variety o
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4.7 INORGANIC NITRATES/NITRITES AND
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Exposure to aromatic amines can be
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4.10 BONE MARROW SUPPRESSION AND LE
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4.12 TOXICITIES THAT INDIRECTLY INV
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4.15 ANTIDOTES FOR HYDROGEN SULFIDE
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REFERENCES AND SUGGESTED READING 10
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112 HEPATOTOXICITY: TOXIC EFFECTS O
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130 NEPHROTOXICITY: TOXIC RESPONSES
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7 Neurotoxicity: Toxic Responses of
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ions moving out of the cell brings
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an effect seen with some neurotoxic
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7.4 INTERACTIONS OF INDUSTRIAL CHEM
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• A study of the patient’s hist
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• Although much of the damage whi
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158 DERMAL AND OCULAR TOXICOLOGY Fi
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160 DERMAL AND OCULAR TOXICOLOGY P4
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162 DERMAL AND OCULAR TOXICOLOGY ca
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164 DERMAL AND OCULAR TOXICOLOGY ke
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166 DERMAL AND OCULAR TOXICOLOGY Fi
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168 DERMAL AND OCULAR TOXICOLOGY
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170 PULMONOTOXICITY: TOXIC EFFECTS
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10 Immunotoxicity: Toxic Effects on
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10.2 BIOLOGY OF THE IMMUNE RESPONSE
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10.2 BIOLOGY OF THE IMMUNE RESPONSE
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certain situations immunosuppressio
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10.5 TESTS FOR DETECTING IMMUNOTOXI
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10.6 SPECIFIC CHEMICALS THAT ADVERS
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10.6 SPECIFIC CHEMICALS THAT ADVERS
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animal origin have also been shown
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The mainstay of treatment of multip
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PART II Specific Areas of Concern P
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210 REPRODUCTIVE TOXICOLOGY continu
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212 REPRODUCTIVE TOXICOLOGY Underst
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214 REPRODUCTIVE TOXICOLOGY spermat
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216 REPRODUCTIVE TOXICOLOGY gonadot
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218 REPRODUCTIVE TOXICOLOGY TABLE 1
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Figure 11.3 Cycle of follicular dev
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222 REPRODUCTIVE TOXICOLOGY Figure
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224 REPRODUCTIVE TOXICOLOGY TABLE 1
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226 Figure 11.5 Developmental tree
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228 REPRODUCTIVE TOXICOLOGY is clea
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230 REPRODUCTIVE TOXICOLOGY genital
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232 REPRODUCTIVE TOXICOLOGY to occu
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234 REPRODUCTIVE TOXICOLOGY these r
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236 REPRODUCTIVE TOXICOLOGY Two imp
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238 REPRODUCTIVE TOXICOLOGY Sundara
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240 MUTAGENESIS AND GENETIC TOXICOL
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248 Figure 12.5 Example of DNA addu
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TABLE 12-3 NTP and Gene-Tox Evaluat
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266 CHEMICAL CARCINOGENESIS 13.1 TH
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268 CHEMICAL CARCINOGENESIS TABLE 1
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270 CHEMICAL CARCINOGENESIS researc
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272 CHEMICAL CARCINOGENESIS Figure
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276
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280 CHEMICAL CARCINOGENESIS 13.4 MO
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286 CHEMICAL CARCINOGENESIS make a
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288 Figure 13.8 A genetic model of
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290 CHEMICAL CARCINOGENESIS Increas
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292 CHEMICAL CARCINOGENESIS may be
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294 CHEMICAL CARCINOGENESIS • The
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296 CHEMICAL CARCINOGENESIS evaluat
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298 CHEMICAL CARCINOGENESIS In rats
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302 CHEMICAL CARCINOGENESIS with ex
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316 CHEMICAL CARCINOGENESIS similar
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422 PROPERTIES AND EFFECTS OF NATUR
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PART III Applications Principles of
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438 RISK ASSESSMENT 18.1 RISK ASSES
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440 RISK ASSESSMENT control populat
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442 RISK ASSESSMENT there are some
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444 RISK ASSESSMENT • It identifi
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446 RISK ASSESSMENT chemical poses
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448 RISK ASSESSMENT • Estimating
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450 RISK ASSESSMENT Figure 18.3 Est
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452 RISK ASSESSMENT • As discusse
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454 RISK ASSESSMENT divided by a de
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456 RISK ASSESSMENT Because low-dos
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458 RISK ASSESSMENT TABLE 18.1 Expe
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460 RISK ASSESSMENT leading to impo
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462 RISK ASSESSMENT characterizatio
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464 RISK ASSESSMENT Figure 18.7 Sim
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466 RISK ASSESSMENT The RPF values
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468 RISK ASSESSMENT producing the e
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470 RISK ASSESSMENT TABLE 18.4b Can
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472 RISK ASSESSMENT TABLE 18.7 Acti
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474 RISK ASSESSMENT A second reason
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476 RISK ASSESSMENT Barnard, R. C.,
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19 Example of Risk Assessment Appli
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19.3 LEAD EXPOSURE AND WOMEN OF CHI
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19.4 PETROLEUM HYDROCARBONS: ASSESS
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19.4 PETROLEUM HYDROCARBONS: ASSESS
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19.5 RISK ASSESSMENT FOR ARSENIC 48
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19.5 RISK ASSESSMENT FOR ARSENIC 48
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19.6 REEVALUATION OF THE CARCINOGEN
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REFERENCES AND SUGGESTED READING RE
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20 Occupational and Environmental H
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20.1 DEFINITION AND SCOPE OF THE PR
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20.4 HUMAN RESOURCES IMPORTANT TO O
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treatment, or medical removal from
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Academic practices welcome complica
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Occupational and environmental medi
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512 EPIDEMIOLOGIC ISSUES IN OCCUPAT
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22 Controlling Occupational and Env
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22.2 EXPOSURE LIMITS 525 The TLVs
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modified “reference doses” to r
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observation process, followed by re
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• Hazard-specific training to ens
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22.3 PROGRAM MANAGEMENT 533 Conside
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Figure 22.1 22.3 PROGRAM MANAGEMENT
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fundamental viability of the work p
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Figure 22.2. 22.3 PROGRAM MANAGEMEN
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• Physical assessment and fit tes
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The study was designed to minimize
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TABLE 22.3 Margins of Safety at For
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top, and numerous slots with smalle
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TABLE 22.5 Comparison of Time-Weigh
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• Housing or building code violat
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• Environmental exposure limits,
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GLOSSARY Glossary absorption The mo
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GLOSSARY 557 antipyretic An agent t
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GLOSSARY 559 chloracne An acne-like
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GLOSSARY 561 eczema A superficial i
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GLOSSARY 563 hemolytic anemia Anemi
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GLOSSARY 565 lipoprotein Any of a g
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GLOSSARY 567 necrosis Death of one
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pernicious anemia The progressive,
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GLOSSARY 571 cells have both endoth
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GLOSSARY 573 tolerance The ability
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576 INDEX Allergic reaction (contin
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578 INDEX Biotransformation (contin
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580 INDEX Children’s health statu
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582 INDEX Diet and nutrition (conti
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584 INDEX Estrogens: endocrine disr
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586 INDEX Hair, toxic agent excreti
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588 INDEX hnmunoglobulins: autoimmu
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590 INDEX Loop of Henle, structure
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592 INDEX Mixed exposure patterns,
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594 INDEX Nutritional deficiencies,
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596 INDEX Pesticides (continued) Pe
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598 INDEX Relative potency factor (
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600 INDEX Solvents (continued) phys
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602 INDEX Tumorigenesis (continued)
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PRINCIPLES OF TOXICOLOGY

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