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A multidisciplinary approach to toxicological screening: II. Developmental toxicity
1ManTech Environmental Technology, Inc., Research Triangle Park, North Carolina, USA.
Abstract:
As part of the validation of an integrated bioassay for systemic toxicity, neurotoxicity, and developmental toxicity, we evaluated the effects of four pesticides, four chlorinated solvents, and two other industrial chemicals in Fischer 344 rats. The pesticides included carbaryl, triadimefon, chlordane, and heptachlor; the solvents included dichloromethane (DCM), carbon tetrachloride, trichloroethylene (TCE), and tetrachloroethylene (perchloroethylene, PER); and the industrial chemicals were di(2-ethylhexyl)phthalate (DEHP) and phenol. In the developmental toxicity studies, timed-pregnant rats were treated by gavage with vehicle or 1 of 2 dose levels of each compound on gestation d 6-19. The dams were allowed to deliver and their litters were examined on postnatal d 1, 3, and 6. Litter weights were determined on postnatal d 1 and 6. Implants were also counted to determine prenatal loss. Maternal toxicity was evidenced by dose-related alterations in weight gain for all 10 compounds. Clinical signs of maternal toxicity were present for all chemicals except chlordane and heptachlor. DEHP exposure resulted in the most pronounced developmental toxicity (high levels of pre- and postnatal mortality), whereas chlordane induced extensive postnatal loss. Of the solvents, only DCM did not cause a high incidence of full-litter resorption. Phenol, heptachlor, triadimefon, and carbaryl showed only slight potential for developmental toxicity. Malformations suggestive of teratogenicity included kinked tail (phenol), microphthalmia (TCE, PER, DEHP), and cleft palate with renal agenesis (DEHP). Although several findings (eye defects caused by TCE and PER, full-litter resorption and delayed parturition caused by PER, and delayed parturition/dystocia associated with triadimefon) have not been previously reported, the results are generally consistent with previous reports and highlight the importance and relative ease of incorporation of developmental evaluations into a multidisciplinary screening battery.
Insights
This study assessed the developmental toxicity of 10 industrial chemicals in rats, finding di(2-ethylhexyl)phthalate (DEHP) and chlordane caused significant harm, while others showed less impact.
Area of Science:
- Toxicology
- Developmental Biology
- Environmental Health
Background:
- Integrated bioassays are crucial for evaluating chemical safety.
- Assessing systemic, neurotoxic, and developmental effects provides a comprehensive toxicity profile.
- Understanding chemical impacts on development is vital for public health protection.
Purpose of the Study:
- To validate an integrated bioassay for toxicity testing.
- To evaluate the developmental toxicity of pesticides, chlorinated solvents, and industrial chemicals.
- To identify specific teratogenic effects and developmental risks associated with chemical exposure.
Main Methods:
- Fischer 344 rats were used in developmental toxicity studies.
- Timed-pregnant rats received gavage administration of 10 chemicals (pesticides, solvents, industrial chemicals) during gestation.
- Dams and litters were monitored for maternal toxicity, litter weights, prenatal loss, and postnatal development.
Main Results:
- All 10 compounds induced maternal toxicity; DEHP and chlordane showed the most severe developmental effects (mortality, postnatal loss).
- Dichloromethane (DCM) was the only solvent not causing high litter resorption.
- Teratogenic malformations included kinked tail (phenol), microphthalmia (TCE, PER, DEHP), and cleft palate with renal agenesis (DEHP).
Conclusions:
- The integrated bioassay effectively identified developmental toxicity risks.
- DEHP and chlordane pose significant developmental hazards.
- The study underscores the importance of incorporating developmental evaluations into multidisciplinary toxicity screening batteries.