Toxicological Evaluation and Limit Values for ... - Miljøstyrelsen

were examined. At the highest and second-highest dose levels, maternaltoxicity was evident, with mortality of two females. No maternal toxicitywas found at 75 mg/kg/day. Post-implantation loss, litter size, foetalweights, and incidence of foetal abnormalities was not affected, even atdose levels which caused maternal toxicity (EU-RAR 1998).NPE effects on the foetusMeyer et al. (1988) administered NPE with 9 or 30 ethylene oxide units(NPE 9, NPE 30) to pregnant rats from gestational day 6 to 15. Doses ofNPE 9 were 50, 250, or 500 mg/kg/day by gavage. A satellite group received500 mg/kg/day by gavage on gestational day 1-20, and two furthergroups received 50 or 500 mg/kg/day dermally on gestational day 6-15.NPE 30 was given at 50, 250, or 1000 mg/kg/day by gavage on gestationalday 6-15, with a satellite group receiving 1000 mg/kg/day on gestationalday 1-20. The rats were killed on day 21 and the foetuses examined.NPE 30 did not cause any toxic effects on dams or foetuses. NPE 9,at 500 mg/kg, caused an increase in extra ribs in the foetuses. This dosecaused a decreased weight gain in the dams.4.4 Genotoxic effectsNonylphenolNP appears to be negative in the Ames test (Salmonella typhimurium),however, a study of sufficient quality has not been found (EU-RAR1998). In an in vitro mammalian cell gene mutation test performed accordingto the OECD test guideline 476, and of GLP quality, and confirmedby a second independent experiment, NP was found non-mutagenic.The dose level may not have been high enough (EU-RAR 1998).Nonylphenol ethoxylateAn NPE with unknown ethylene oxide chain length was found negativein the Ames test, using Salmonella typhimurium (CIR 1983). NPEs with9 or 30 ethylene oxide units have been found negative in the Ames test(Salmonella typhimurium) (Meyer et al. 1988).4.5 Carcinogenic effectsFor nonylphenol, no data have been found (EU-RAR 1998).NPEs with 4 and 9 ethoxylene oxide units have been administered orallyto rats for 2 years (Smyth & Calandra 1969). The group size was 35 ofeach sex for NPE with 4 ethylene oxide units, and 5 of each sex wereinterim sacrificed at 12 months. Histopathological examination was doneon 28 tissues on 5 rats of each sex from the control and highest dosegroup.For NPE with 9 ethylene oxide units the group size was 36 of each sex,with 16 rats of each sex interim sacrificed at 6 and 12 months. Histopathologywas performed on 11 tissues and all neoplasms.No increased frequency of tumours was reported in either study.28