ORIGINAL PAPER
Developmental toxicity of N-methylaniline following prenatal oral administration in rats
More details
Hide details
1
Nofer Institute of Occupational Medicine, Łódź, Poland
(Department of Toxicology and Carcinogenesis)
Corresponding author
Krystyna Sitarek
Nofer Institute of Occupational Medicine, Department of Toxicology and Carcinogenesis, św. Teresy 8, 91-348 Łódź, Poland
Int J Occup Med Environ Health. 2016;29(3):479-92
KEYWORDS
TOPICS
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.