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46151802.DER.pdf
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46151802
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Acephate
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30560-19-1
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103301
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Hoberman, A. (2003) Oral (Gavage) Developmental Neurotoxicity Study of Acephate Technical in Rats. Project Number: VP/23747, 200300344, ARGUS/222/002. Unpublished study prepared by Argus Research Laboratories, Inc. 878 p.
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2003.0
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In a developmental neurotoxicity study (MRID 46151802) Acephate technical (99.2% a.i.; Lot #: AS 40s) in deionized water was administered daily by oral gavage to pregnant Crl:CD® (SD)IGS BR VAF/Plus® rats (25/dose) at doses of 0, 0.5, 1, or 10 mg/kg/day from gestation day (GD) 6 through lactation day (LD) 6. Additionally the F1 pups were similarly dosed on postnatal days (PNDs) 7-21. Dams were allowed to deliver naturally and were sacrificed on LD 6. On PND 4, litters were standardized to 10 pups/litter (5 males and 5 females when possible); the remaining offspring were sacrificed and examined grossly and for cholinesterase activity. Subsequently, 10 pups/sex/group were allocated to Subsets 1-4 and up to 10 pups/sex/group to Subset 5. Selected subsets were examined for detailed clinical and functional observational battery, motor activity, auditory startle habituation, passive avoidance and water maze learning and memory tests, brain weight, neuropathology, and/or brain and blood cholinesterase determinations. Pups were weaned on PND 21, and all offspring were sacrificed by PND 71.
No treatment-related effect was observed on maternal mortality, clinical signs, abbreviated functional observations, body weight, food consumption, reproductive performance, and gross pathology.
The maternal NOAEL is 10 mg/kg/day (HDT). A maternal LOAEL is not established.
Treatment had no adverse effects on offspring survival, body weight, body weight gain, food consumption, clinical signs, FOB, developmental landmarks, auditory startle reflex, learning and memory, brain weights, brain morphology or neuropathology. Assessment for motor activity revealed a non-significant but dose-related decrease in the number of movements (19% decreased at 1 mg/kg/day to 30% decreased at 10 mg/kg/day) that was accompanied by non-significant but comparable dose-related decreases in time spent in movement (19% decreased at 1 mg/kg/day to 28% decreased at 10 mg/kg/day) in females on Day 21. However, it was determined that no conclusions can be drawn regarding the effect of acephate on motor activity because the variability in the data was so high.
No treatment-related cholinesterase inhibition (ChEI) was seen in the brains, plasma or red blood cells of male or female pups at PND 4. On Day 21, dose-depended and statistically significant ChEI of the brain were seen. Inhibition at the low, mid and high dose groups were 29 %, 34% and 62%, respectively, in males and 25%, 25%, and 58%, respectively, in females. There were also significant (p<0.01) reductions in plasma (46% in males and 43% in female) and RBC (50% in males and 63% in females) ChEI in males at the high-dose males at PND 21.
The offspring LOAEL is 0.5 mg/kg/day (LDT), based on statistically significant and dose-depended inhibition of brain cholinesterase activity in male and female pups on Day 21. An offspring NOAEL was not established.
This study is classified Acceptable/NonGuideline and may be used for regulatory purposes. It does not, however, satisfy the guideline requirement for a developmental neurotoxicity study in rats (OPPTS 870.6300, §83-6); OECD 426 (draft) due to the inadequacies in the assessment of motor activity in the offspring and the pending comprehensive review of the positive control data.
[This classification scheme is applicable only to Developmental Neurotoxicity (DNT) studies. The DNT Work Group determined that this study can be classified as Acceptable. This study does not satisfy the guideline requirements for a developmental neurotoxicity study and is classified as NonGuideline pending review of all available positive control data. 01/24/2006 J. Rowland ]
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Developmental-Neurotoxicity
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NA [870.6300, Developmental neurotoxicity study]
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Oral
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No Duration Period; gavage; maternal GD 6 to LD 6;
F1 pups PND 7 to PND 21;positive control MRID 46179301
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52318.0
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2006-01-24
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2006-02-08
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Added by
Madison Feshuk
on Apr 25, 2022
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