Two-generation reproductive toxicity study of inhaled toluene diisocyanate vapor in CD rats
| Autor: | I. M. Pritts, L. C. Fisher, Teresa L. Neeper-Bradley, Timothy D. Landry, Rochelle W. Tyl, Patricia E. Losco, Darol E. Dodd, James P. Lyon |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Atmosphere Exposure Chambers medicine.medical_specialty No-observed-adverse-effect level Litter Size Physiology Biology Weight Gain Toxicology Rats Sprague-Dawley chemistry.chemical_compound Pregnancy Occupational Exposure Internal medicine Lactation Administration Inhalation medicine Animals Sex Ratio Rhinitis Toluene diisocyanate Reproduction Body Weight Teratology Rats Teratogens medicine.anatomical_structure Endocrinology Fetal Weight chemistry Toxicity Gestation Female Toluene 2 4-Diisocyanate medicine.symptom Reproductive toxicity Weight gain |
| Zdroj: | Toxicological Sciences. 52:258-268 |
| ISSN: | 1096-0929 |
| Popis: | Twenty-eight 42-day-old pups/sex/group (F0) were exposed to toluene diisocyanate vapor (TDI; 80% 2,4-TDI, 20% 2,6-TDI) by inhalation at 0.0, 0.02, 0.08, or 0.3 ppm, 6 h/day, 5 days/week, for 10 weeks, then mated within groups for 3 weeks, with exposure 7 days/week during mating, gestation, and lactation. F0 maternal animals were not exposed from gestational day (gd) 20 through postnatal day (pnd) 4; maternal exposures resumed on pnd 5. Twenty-eight weanlings/sex/group continued exposure for 12 weeks (starting on pnd 28) and were bred as described above. F0 and F1 parents and ten F1 and F2 weanlings/sex/group were necropsied, and adult reproductive organs, pituitary, liver, kidneys, and upper respiratory tract (target organs) were evaluated histologically in ten/sex/group. Adult toxicity was observed in both sexes and generations at 0.08 and 0.3 ppm, including occasional reductions in body weights and weight gain, clinical signs of toxicity at 0.08 and 0.3 ppm, and histologic changes in the nasal cavities at 0.02, 0.08, and 0.3 ppm (including rhinitis, a nonspecific response to an irritating vapor, at all concentrations). There was no reproductive toxicity, reproductive organ pathology, or effect on gestation or lactation at any exposure concentration. Postnatal toxicity and reduced body weights and weight gains during lactation occurred only in F2 litters at 0.08 and 0.3 ppm. Therefore, under the conditions of this study, a no observed adverse effect level (NOAEL) was not determined for adult toxicity; the NOAEL for reproductive toxicity was at least 0.3 ppm, and the NOAEL for postnatal toxicity was 0.02 ppm. |
| Databáze: | OpenAIRE |
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