Developmental toxicity of N-methylaniline following prenatal oral administration in rats.

Abstract

OBJECTIVES The objective of the study was to assess prenatal toxicity of N-methylaniline (NMA) administered by gavage to pregnant female rats. MATERIAL AND METHODS Pregnant female rats were administered N-methylaniline in corn oil by gavage at daily doses of 0.8 mg/kg of body weight (b.w.), 4 mg/kg b.w., 20 mg/kg b.w. and 100 mg/kg b.w. from implantation (the 5th day post mating) to the day prior to the scheduled caesarean section (the 20th day of pregnancy). General behavior, body weight, food and water consumption, hematological, biochemical analyses and pathomorphological changes of the dams were recorded. RESULTS All the females survived until the end of the study. The test substance was toxic to pregnant females, even at the lowest of the used doses, i.e., 0.8 mg/kg b.w./day. Lower weight gain during pregnancy and significantly higher NMA-dose-dependent absolute weight of the organs were noted in the exposed females. The females from the groups exposed at doses of 20 mg/kg b.w./day and 100 mg/kg b.w./day developed anemia and showed higher concentrations of free thyroxine (FT3) and free triiodothyronine (FT4) thyroid hormones. Total protein concentration exhibited an increase in all the exposed groups of females. In the prenatal toxicity study, administration of N-methylaniline throughout the embryonic and fetal periods produced embryotoxic effects at doses ranging 4-100 mg/kg b.w./day. CONCLUSIONS Considering the data obtained in this study, it is reasonable to assume that N-methylaniline administered orally to pregnant rats is toxic for mothers even at a low dose of 0.8 mg/kg b.w./day. However, this dose was not associated with any significant effects to their offspring. This prenatal exposure level may be considered as no-observed-adverse-effect level (NOAEL) for the progeny and a dose of 4 mg/kg b.w./day as the lowest-observed-adverse-effect level (LOAEL) for the progeny.

DOI: 10.13075/ijomeh.1896.00571

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@article{Sitarek2016DevelopmentalTO, title={Developmental toxicity of N-methylaniline following prenatal oral administration in rats.}, author={Krystyna Sitarek and Jolanta Gromadzińska and Jan Stetkiewicz and Piotr Lutz and Magdalena Beata Kr{\'o}l and Katarzyna Domeradzka-Gajda and Wojciech Wąsowicz}, journal={International journal of occupational medicine and environmental health}, year={2016}, volume={29 3}, pages={479-92} }