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Effects of dinocap on otolith development: evaluation of mouse and hamster fetuses at term
J M Rogers1, L M Burkhead, B D Barbee
1Perinatal Toxicology Branch, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Abstract:
The morphology of otoliths in CD-1 mouse and Syrian hamster fetuses exposed to the fungicide dinocap were evaluated at the end of gestation. Pregnant mice were dosed by gavage with 0, 10, 15, 30, or 60 mg/kg/day dinocap in corn oil on days 7-16 of gestation. Pregnant hamsters were dosed by the same route with 0, 50, 100, or 200 mg/kg/day on days 7-14 of gestation. At the end of gestation (day 18 in mice, day 15 in hamsters) dams were killed and all fetuses were removed and fixed overnight in 70% ethanol. Fetal heads were then removed, left in 70% ethanol for at least 3 days, and then dehydrated in a graded ethanol series and cleared with methyl salicylate. Otoliths were examined by darkfield microscopy, and each otolith was scored for morphological completeness on a scale of 0 to 3. Otolith development was complete by day 18 of gestation in control mouse fetuses. Otolith development was complete in many, but not all, of the hamster fetuses by day 15 of gestation. In the mouse, dinocap exposure inhibited fetal otolith formation in a dose-related manner, with a significant effect on total otolith score occurring at 10 mg/kg/day and above. Dinocap affected otolith formation in the hamster only at 100 mg/kg/day (200 mg/kg/day was embryolethal), concomitant with severe maternotoxicity and fetotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
The fungicide dinocap disrupted fetal otolith development in mice and hamsters. Exposure to dinocap caused dose-related inhibition of otolith formation in mouse fetuses and affected hamster otoliths at higher doses.
Area of Science:
- Developmental Toxicology
- Teratology
- Otolith Morphology
Background:
- Fungicides can pose risks to developing organisms.
- Otoliths are crucial inner ear structures for balance and hearing.
- Understanding developmental toxicity of environmental agents is vital.
Purpose of the Study:
- To evaluate the effects of dinocap exposure on fetal otolith morphology.
- To determine dose-response relationships for dinocap's teratogenic potential on otoliths.
Main Methods:
- Pregnant CD-1 mice and Syrian hamsters were administered dinocap via gavage during critical gestation periods.
- Fetal heads were collected at term, and otoliths were isolated and prepared for microscopy.
- Otolith morphological completeness was assessed using darkfield microscopy and a scoring system.
Main Results:
- Dinocap exposure inhibited fetal otolith formation in mice in a dose-dependent manner, with effects seen at 10 mg/kg/day and higher.
- In hamsters, dinocap affected otolith formation at 100 mg/kg/day; higher doses (200 mg/kg/day) were embryolethal and caused severe maternal and fetal toxicity.
- Otolith development was complete by day 18 in control mouse fetuses and by day 15 in most control hamster fetuses.
Conclusions:
- Dinocap exhibits teratogenic effects on otolith development in both mouse and hamster models.
- The fungicide poses a developmental risk, particularly to otolith formation, with varying sensitivity between species.
- Further investigation into the mechanisms of dinocap's ototoxicity is warranted.