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44710501.der.pdf
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44710501
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Triallate
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2303-17-5
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078802
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Lemen, J.; Kaempfe, A.; Thake, D. et al. (1998) Developmental Neurotoxicity Study of Triallate Administered to Pregnant/Lactating CD Rats: Lab Project Number: ML-97-129: MSE-N 97002: RD 1451. Unpublished study prepared by Monsanto Company. 1528 p.
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1998.0
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Triallate: In a developmental neurotoxicity study (MRID 4471050), 21-22 pregnant Sprague-Dawley rats/group were administered Triallate (96.84% a.i.) in corn oil by gavage from gestation day 6 through lactation day 20 at 0, 10, 30, or 60 mg/kg/day. At postnatal day 4, the pups were culled and assigned to three separate subsets for different investigational programs.
At 60 mg/kg/day maternal toxicity was limited to reduction in body weight gains during gestation days 6-9 (decr. 67%, p<=0.01) and gestation days 6-12 (decr. 32%, p<=0.05) and reduction in food consumption during gestation days 6-12 (decr. 15%, p<=0.01). The maternal LOAEL was 60 mg/kg/day, based on reductions in body weight gains and food consumption. The maternal toxicity NOAEL was 30 mg/kg/day.
At 60 mg/kg/day there were several parameters affected in the developing offspring. Body weight was reduced (6% in males and 7% in females at postnatal days 17 and 21, p < 0.05 or .01) and remained about 4-6% lower to postnatal day 87. Reduced forelimb grip strength (decr. 23%, p<=0.05) was possibly associated with the reduced body weight. Increased motor activity was observed at postnatal day (PND) 17 (incr. 72% M, p<=0.01 and incr. 57% F, p < 0.05 ), 21(incr. 73% M, p<=0.01 and incr. 54% F, ns), and 58 (incr. 21% M, p<=0.05 and 21% F, ns) and at PND 84 (incr. 7% M, ns and incr. 19% M [correct F], p < 0.05). When the motor activity data from PND 58 and 84 were combined and the litter was used as the statistical unit, significance was found in both males (incr. 15%, p<=0.05) and females (incr. 21%, p<=0.01). There were significant decreases in passive avoidance latency (a measure of acquisition and memory) in females at PND 61/62 (144%, p<=0.05) and when results from PND 61/62 1) and 75 (using a different set of rats) were combined and analyzed by litter (decr. 34%, p<=0.05). Results from PND 23 (decr. 58%) and PND 75 (decr. 22%) were not significantly different, but were decreased, indicating a general decrease in latency at all time points for females only. A non-significant increase (4/26 treated vs 1/27 controls) in the number of hyperactive females was also noted and only considered to be of toxicological concern because of the concomitant differences in the related observations of motor activity and passive avoidance. The developmental neurotoxicity LOAEL is 60 mg/kg/day, based on increased activity. The developmental neurotoxicity NOAEL is 30 mg/kg/day.
Classification. This study in the rat is classified acceptable/guideline (§83-6) and does satisfy the guideline requirements for a developmental neurotoxicity study. Deviations from the Guidelines were approved by the Agency prior to the conduct of the study and are documented in the report.
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Developmental-Neurotoxicity
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NA [83-6, Developmental Neurotoxicity]
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Oral
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No Duration Period; GD 6 to LD 20
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13524.0
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1999-06-21
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2021-03-24
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kept file with cover memo that was previously cleared
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Added by
Madison Feshuk
on Apr 25, 2022
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