Subchronic Thyroid Toxicity Evaluation of 4,4′-Methylenebis(N,N′-Dimethyl)Aniline in Fischer 344 Rats
| Autor: | Mark A. Sochaski, Kathleen A. Funk, Linda J. Pluta, Darol E. Dodd, Russell S. Thomas |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
endocrine system
medicine.medical_specialty No-observed-adverse-effect level Health Toxicology and Mutagenesis Thyroid Gland Administration Oral Thyrotropin Toxicology Follicular cell Muscle hypertrophy Random Allocation Internal medicine medicine Animals Thyroid Neoplasms No-Observed-Adverse-Effect Level Aniline Compounds Hyperplasia Triiodothyronine Dose-Response Relationship Drug business.industry Thyroid Hypertrophy Organ Size medicine.disease Rats Inbred F344 Rats Thyroxine medicine.anatomical_structure Endocrinology Toxicity Carcinogens Environmental Pollutants Female Indicators and Reagents Histopathology business |
| Zdroj: | Journal of Toxicology and Environmental Health, Part A. 75:637-648 |
| ISSN: | 1087-2620 1528-7394 |
| DOI: | 10.1080/15287394.2012.688481 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|