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CUMULATIVE EFFECTS OF THIRAM AND AMITRAZ ON PREGNANCY MAINTENANCE AND DEVELOPMENT IN THE RAT
Citation:
Best, D S., M G. Narotsky, AND R L. Cooper. CUMULATIVE EFFECTS OF THIRAM AND AMITRAZ ON PREGNANCY MAINTENANCE AND DEVELOPMENT IN THE RAT. Presented at Society of Toxicology, New Orleans, LA, March 6-10, 2005.
Description:
Cumulative Effects of Thiram and Amitraz on Pregnancy Maintenance and Development in the Rat.
Deborah S. Best, Michael G. Narotsky, and Ralph L. Cooper
Reproductive Toxicology Division, NHEERL, ORD, US Environmental Protection Agency, Research Triangle Park, NC
Amitraz and thiram are pesticides that have been shown to disrupt luteinizing hormone (LH) secretion in rats, albeit by different mechanisms. Amitraz acts via ?-noradrenergic antagonism; whereas thiram inhibits norepinephrine synthesis. Here, we sought to evaluate the cumulative effects of amitraz and thiram on pregnancy maintenance when administered during the LH-dependent period of pregnancy (days 7-10). To assess dose additivity, in Experiment 1, F344 rats were administered amitraz at 40 mg/kg (A40), thiram at 25 mg/kg (T25), or the two combined (AT-high) at 20 and 12.5 mg/kg, respectively, by gavage on gestation days (GD) 6-10. Controls received vehicle (1% methylcellulose). In Experiment 2, all doses were halved to yield treatments of A20, T12.5, and AT-low (A10 + T6.25). Tail-blood samples were taken from selected dams for assay of serum LH. Litters were examined on postnatal days (PD) 1 and 6. Full-litter resorption (FLR) was observed in 23 (79%), 8 (33%), and 18 (64%) of the dams in the A40, T25, and AT-high groups, respectively, and in 7 (41%), 3 (25%), and 1 (7%) of the dams in the A20, T12.5, and AT-low groups, respectively. One (5%) control dam had full-litter loss, but, unlike the other cases, the loss appeared to occur near term. Reduced serum LH levels were observed on GD 10 in A40, T25, and AT-high dams with FLR, and in A40 dams with live litters. For dams with surviving litters, delayed parturition was noted in the A40, T25, and AT-high groups. Surviving A40 litters had increased resorption rates and increased incidences of eye defects (microphthalmia, anophthalmia). Pup weights were reduced on PD 1 at A40 and T25. Thus, both chemicals, alone and in combination at the high doses, caused FLR and delayed parturition; these findings are consistent with dose additivity. Whereas the low doses of each chemical alone also caused FLR, dose additivity was not clearly demonstrated by the AT-low combination. [This abstract does not necessarily reflect EPA policy.]