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The mouse teratogen dinocap has lower A/D ratios and is not teratogenic in the rat and hamster
J M Rogers1, B Barbee, L M Burkhead
1Perinatal Toxicology Branch, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Abstract:
The fungicide dinocap is currently used in the control of powdery mildew. We have reported that dinocap is teratogenic in the CD-1 mouse, causing cleft palate, otolith defects, and fetal weight deficits well below maternotoxic dose levels. In this study the maternal and fetal toxicity of dinocap was determined in the Sprague-Dawley rat and Syrian golden hamster, and adult-to-developmental (A/D) toxicity ratios were calculated and compared with the previously established A/D ratio of dinocap in the mouse. Dinocap in corn oil was administered by gavage to pregnant rats on gestation days 7-20 (0, 100, 150, 200 mg/kg/day) and to hamsters on gestation days 7-14 (0, 12.5, 25, 50, 75, 100, 200 mg/kg/day). Dams were killed on day 21 (rat) or day 15 (hamster), and litters were removed, counted, and weighed; half of each litter was necropsied for soft tissue defects, and the remaining half was processed for skeletal examination. In the rat, maternal extrauterine weight gain was significantly affected at 150 and 200 mg/kg/day, relative liver weight was elevated at 100 mg/kg/day and above, and fetal weight was lower at 150 and 200 mg/kg/day. In the hamster, maternal extrauterine weight was lower at 12.5 mg/kg/day and above; fetal weight was reduced, and the incidence of dilated renal pelvis was higher, at 25 mg/kg/day and above. Thus the A/D ratios for dinocap in the rat and hamster are similar, approximately 1.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Dinocap, a fungicide, shows teratogenic effects in rats and hamsters, similar to mice. This study assessed dinocap
Area of Science:
- Toxicology
- Developmental Biology
- Environmental Science
Background:
- Dinocap is a fungicide used for powdery mildew control.
- Previous studies indicated dinocap is teratogenic in mice, causing birth defects at low doses.
Purpose of the Study:
- To determine the maternal and fetal toxicity of dinocap in Sprague-Dawley rats and Syrian golden hamsters.
- To compare the adult-to-developmental (A/D) toxicity ratios of dinocap across species.
Main Methods:
- Pregnant rats and hamsters were administered dinocap via gavage during critical gestation periods.
- Maternal weight, liver weight, fetal weight, and developmental defects (soft tissue and skeletal) were assessed.
Main Results:
- In rats, maternal weight gain and fetal weight were reduced at higher doses; liver weight increased.
- In hamsters, maternal weight, fetal weight, and renal pelvis dilation were affected at lower doses.
- Adult-to-developmental (A/D) toxicity ratios for dinocap were similar in rats and hamsters, approximately 1.
Conclusions:
- Dinocap exhibits maternal and developmental toxicity in rats and hamsters.
- The toxicity profile and A/D ratios suggest a consistent teratogenic risk across these species.
- Findings highlight the importance of considering dinocap's developmental toxicity in risk assessments.