title: Developmental toxicity of N-methylaniline following prenatal oral administration in rats.
abstract: OBJECTIVE
  The objective of the study was to assess prenatal toxicity of N-methylaniline (NMA) administered by gavage to pregnant female rats.
  
  
  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.
authors.affiliation: Nofer Institute of Occupational Medicine, Łódź, Poland (Department of Toxicology and Carcinogenesis). ksitarek@imp.lodz.pl.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Sitarek
authors.affiliation: Nofer Institute of Occupational Medicine, Łódź, Poland (Department of Toxicology and Carcinogenesis). jola@imp.lodz.pl.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Gromadzińska
authors.affiliation: Nofer Institute of Occupational Medicine, Łódź, Poland (Department of Toxicology and Carcinogenesis). janstet@imp.lodz.pl.
authors.forename: Jan
authors.initials: J
authors.lastname: Stetkiewicz
authors.affiliation: Nofer Institute of Occupational Medicine, Łódź, Poland (Department of Toxicology and Carcinogenesis). astra@imp.lodz.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Lutz
authors.affiliation: Nofer Institute of Occupational Medicine, Łódź, Poland (Department of Toxicology and Carcinogenesis). lenakrol@imp.lodz.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Król
authors.affiliation: Nofer Institute of Occupational Medicine, Łódź, Poland (Department of Toxicology and Carcinogenesis). kachada@imp.lodz.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Domeradzka-Gajda
authors.affiliation: Nofer Institute of Occupational Medicine, Łódź, Poland (Department of Toxicology and Carcinogenesis). wojciech@imp.lodz.pl.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Wąsowicz
mesh_terms: D000284:Administration, Oral; D000740:Anemia / Q000139:chemically induced; D000814:Aniline Compounds / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D006454:Hemoglobins / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000814:Aniline Compounds; D006454:Hemoglobins; D014284:Triiodothyronine; D013974:Thyroxine; C021313:methylaniline
keywords: N-methylaniline; NMA; developmental toxicity; metHb; rat; toxicity