Toxicological Evaluation and Limit Values for ... - MiljÃ¸styrelsen

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decrease with increasing length of the ethylene oxide chain (Talmage1994).AirNP released to the atmosphere will exist in the vapour phase and isthought to be degraded by reaction with photochemically produced hydroxylradicals, with a calculated half-life of 0.3 days.No data have been found for NPE.WaterAbiotic degradation of NP is negligible. Biodegradation does not readilytake place. The half-life in surface water may be around 30 days (EU-RAR 1998).No data have been found for NPE.SoilNP in soil will have no mobility (HSDB 1997). Biodegradation of NP insoil is slow, and may occur in steps, each step characterised by a certainrate of degradation, as shown in field tests. The half-life in soil is probablyaround 30 days (EU-RAR 1998).No data have been found for NPE.BioaccumulationNP bioconcentrates to a significant extent in aquatic species. Excretionand metabolism is rapid (EU-RAR 1998).No data have been found for NPE.1.6 Human exposureThe possible routes of human exposure to NP and NPEs are dermal contactand inhalation by workers involved in the manufacture and use, dermaland inhalation exposure of consumers from household pesticideproducts, dermal contact to cleaning products and cosmetics, mucousmembrane contact to spermicides; inhalatory exposure via the environmentthrough air, and oral exposure via the environment through drinkingwater and food.8
2 Toxicokinetics2.1 Absorption, distributionInhalationNo data have been found for either NP or NPE.However, on the basis that NP appears to be readily absorbed from thegastrointestinal tract and in view of its high partition coefficient (approximately4.5) (EU-RAR 1998) it is assumed that significant absorptionvia the inhalation route will occur.Oral intakeKnaak et al. (1966) administered 14 C-labelled nonylphenol, 14 C-labellednonylphenol ethoxylate (9 ethylene oxide units), and 14 C-labelled polyoxyethylene,orally or intraperitoneally to male rats (4 rats per group).Daily urine and faeces samples were collected and analysed for 14 C overa 7-day period, while exhaled CO 2 samples were collected and analysedfor 14 C over a 4-day period. For NP and NPE, a similar pattern of excretionwas found. About 70% of the administered radioactivity was excretedvia faeces, and 20% via the urine. Most of the radioactivity wasexcreted within 4 days after administration. No radioactivity was detectedin exhaled CO 2 . The main part of the urinary NP and NPE metaboliteswere found to be acidic and were believed to be glucuronic acidconjugates of nonylphenol.The toxicokinetic behaviour of radiolabelled nonylphenol was investigatedin two male volunteers, aged 29 and 58 years (Müller 1997 -quoted in EU-RAR 1998). Ring 14 C-labelled nonylphenol was administeredto one volunteer as a single oral dose of 5 mg (66 µg/kg bodyweight)and to the second volunteer as a single intravenous dose of 1 mg(14 µg/kg). Blood, urine and faeces were collected from the first volunteerat intervals for up to 56 hours after administration. Blood samplesonly were taken from the second volunteer, for up 24 hours. The biologicalsamples were analysed for nonylphenol and nonylphenol conjugates(glucuronide and sulphate) by gas chromatography/mass spectrometry (itis not clear why radiolabelled nonylphenol was used). Recovery experimentsusing spiked blood, urine, faeces and adipose tissue samples confirmedthe efficiency of the analytical extraction technique. Followingoral administration, the concentration of nonylphenol and nonylphenolpresent as conjugates in the blood both peaked at about 1 hour; peakconcentration of nonylphenol present as a conjugate was 86 ng/g blood,which was some 100-fold greater than that of unconjugated nonylphenol.For intravenous administration, the highest concentrations of nonylphenol,at 0.6 and 0.2 ng/g blood for unconjugated and conjugated compound,respectively, were seen at the first sampling point of 30 minutes;at all time points the concentrations of unconjugated and conjugatednonylphenol were of the same order of magnitude. For both the oral andintravenous routes, the time courses of blood concentration were indicativeof an initial phase of distribution from the blood to a second compartment(presumably the lipid compartment) followed by a slowerelimination phase. Comparison of the AUCs for the oral and intravenous9
Page 1 and 2: Environmental Project No. 512 2000M
Page 3 and 4: 1 General description1.1 IdentityNo
Page 5 and 6: with varying average lengths of the
Page 7: 1.4 Environmental occurrenceNP and
Page 11 and 12: 3 Human toxicity3.1 Short term toxi
Page 13 and 14: 9 concentrated vapour atambient tem
Page 15 and 16: Table 3. Dermal LD 50 -values in ra
Page 17 and 18: Table 4a Number of animals with his
Page 19 and 20: with 40 ethylene oxide units, no ef
Page 21 and 22: *) In the original report, dose was
Page 23 and 24: Table 7 Results of studies in dogs
Page 25 and 26: Dermal contactNo data have been fou
Page 27 and 28: generation reproduction toxicity st
Page 30 and 31: 5 Regulations, limit valuesAmbient
Page 32 and 33: units is low, as LD 50 values varyi
Page 34 and 35: 7 EvaluationA study in humans invol
Page 36 and 37: mg/kg/day were found in rats. In do
Page 38 and 39: = 25 mg/kg soilNPEBased on the TDI
Page 40 and 41: is set at the limit value. A C-valu
Page 42 and 43: Odum J, Lefevre PA, Tittensor S, Pa

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