Subchronic thyroid toxicity evaluation of 4,4'-methylenebis(N,N'-dimethyl)aniline in Fischer 344 rats.
Female F344 rats were exposed to 4,4'-methylenebis(N,N'-dimethyl)aniline (MDA) by dietary feed at concentrations of 0, 50, 200, 375, 500, or 750 ppm for 5 d, 2 wk, 4 wk, and 13 wk duration. Endpoints evaluated included clinical observations, body weights, thyroid weights, serum thyroid hormones, blood MDA, gross pathology, and thyroid histopathology. There were no MDA exposure-related clinical signs of toxicity. Mean body weight decreased 5% compared to control in the 750 ppm group during study wk 6 through 13. Serum TSH increased and serum T4 and T3 levels decreased with increasing feed concentrations of MDA and time of exposure. Thyroid weight increases were both concentration- and exposure time-dependent and statistically significant at ≥375 ppm. Incidence and severity of decreased colloid, follicular cell hypertrophy and follicular cell hyperplasia were also related to MDA concentration and exposure time. A no-observed-adverse-effect level (NOAEL) of 200 ppm was selected based on the statistically significant increase in incidence of follicular cell hyperplasia at concentrations ≥375 ppm.
The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, USA.
Darol E
DE
Dodd
Linda J
LJ
Pluta
Mark A
MA
Sochaski
Kathleen A
KA
Funk
Russell S
RS
Thomas
D000284:Administration, Oral; D000814:Aniline Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D006965:Hyperplasia; D006984:Hypertrophy; D007202:Indicators and Reagents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D013961:Thyroid Gland / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D013964:Thyroid Neoplasms / Q000139:chemically induced; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
C574620:4,4'-methylenebis(N,N'-dimethyl)aniline; D000814:Aniline Compounds; D002273:Carcinogens; D004785:Environmental Pollutants; D007202:Indicators and Reagents; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine