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45068601.DER.pdf
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45068601
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Aldicarb
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116-06-3
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098301
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Moser, V. (1999) Comparison of Aldicarb and Methamidophos Neurotoxicity at Different Ages in the Rat: Behavior and Biochemical Parameters. Toxicology and Applied Pharmacology 157:94-106.
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1999.0
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Aldicarb: In this special acute neurotoxicity study (MRID 45068601), groups of 14 Long-Evans CRL:(LE)BR rats of 3 different ages (post-natal day (PND) 17; PND 27; or >PND 67) were given acute oral doses by gavage between 0.05 and 0.35 mg/kg of Aldicarb (>99%) in corn oil and their survival, behavior, and cholinesterase levels in whole blood and brain assessed. Using sequential dosing of groups of rats (first 2-3; then 5-10), the highest dose that produced clear signs of cholinergic toxicity without death or considerable weight loss was determined and called a maximum tolerated dose (MTD). For the full study, PND 17 rat doses were 0, 0.05, 0.1, or 0.18 mg/kg. PND 27 rat doses were 0, 0.08, 0.15, and 0.26 mg/kg. Adult rats received 0, 0.1, 0.2, and 0.35 mg/kg. 10 rats/sex/dose were examined by a Functional Observational Battery (FOB) and a Motor Activity test (MA) prior to the study, at the time of peak effect, 1 hour after dosing for the FOB and immediately after the FOB for MA; and on post-dosing days 1, 3, and 7. Blood (whole blood) and whole brain cholinesterase determinations were made on 4 rats/sex/dose at 1 hour after dosing, and, for the highest dose level, 24 and 72 hours after dosing, by the radiometric method.
The MTDs were: for PND 17 rats, 0.18 mg/kg; for PND 27 rats, 0.26 mg/kg; and for adult rats 0.35 mg/kg.
PND 17 rats showed only a few behavioral effects after their highest dose (0.18 mg/kg), tremors, gait changes/ataxia, and a lesser effect on the righting response. PND 27 and adult rats showed many significant behavioral responses at doses of 0.1 mg/kg (adults) or 0.15 mg/kg (PND 27) and higher. The LOAEL for behavioral effects for PND 27 pups was 0.08 mg/kg, where a significant decrease in the tail pinch response was seen in males. For adults, at 0.1 mg/kg, there were significant effects on tremors, miosis, and decreased motor activity in both sexes, gait changes/ataxia and decreased arousal in females. In automated motor activity, aldicarb produced dose related decreases in PND 27 and adult rats (5-80%), but almost no decreases in PND 17 rats (<20%).
All of the doses caused significant inhibition in the blood for all 3 ages, and all but the lowest dose for adults (0.18 mg/kg) and 0.05 mg/kg for PND 17 females (20%) caused significant inhibition in the brain as well. For brain ChEs, there was significantly more inhibition for PND 17 rats than adults based on their ED50 values (0.12 mg/kg vs 0.29mg/kg, males; 0.15 mg/kg vs 0.28 mg/kg, females). There were no significant differences found in levels of blood ChE among the 3 age groups. At 0.05 mg/kg in PND 17 rats, (lowest dose tested) blood inhibition was 66-75%, and brain inhibition was 30-15% (males, females respectively).
In conclusion, this study shows a 2 fold increase in sensitivity in terms of lethality and brain ChE inhibition for PND 17 rats in comparison to adults (MTD: PND 17 rats, 0.18 mg/kg vs. adults, 0.35 mg/kg; Brain ChE ED50s: 0.12 mg/kg vs 0.29mg/kg, males; 0.15 mg/kg vs 0.28 mg/kg, females, PND 17 vs. adults) but no differences in neurobehavioral effects, or blood ChE inhibition.
LOAEL= 0.05 mg/kg for PND 17 rats based on blood and brain ChE inhibition. NOAEL= < 0.05 mg/kg.
Not classified.
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Neurotoxicity-Acute
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NA [81-8, Acute neurotoxicity screen study in rats|81-9, Developmental neurotoxicity (use 870.3650 or 870.6300 instead of this)]
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Oral
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Treatment Duration: 1 Dose; special study
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14219.0
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2007-10-16
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2021-02-17
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Added by
Madison Feshuk
on Apr 25, 2022
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