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45630301.der.pdf
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45630301
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Methyl parathion
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298-00-0
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053501
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Beyrouty, P. (2002) A Developmental Neurotoxicity Study of Orally Administered Methyl Parathion in the Rat: Lab Project Number: 97574. Unpublished study prepared by ClinTrials BioResearch Ltd. 2132 p.
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2002.0
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In a developmental neurotoxicity study (MRID 45630301), Methyl Parathion (96.8% a.i., lot # 621-BSe-20A) was administered to 32 pregnant female Crl:CD7 (SD) IGS BR rats/group by gavage at doses of 0, 0.03, 0.30, or 0.60 mg/kg/day from gestation day 6 through postnatal day 10. The resulting offspring were dosed on lactation days 11-21. A Functional Observational Battery (FOB) was performed on all dams on gestation days 12 and 18 and on lactation days 4 and 10. On postnatal day 4, litters were culled to yield four males and four females (as closely as possible). Randomly-selected pups (at least 10/sex/dose) were selected for either the FOB on lactation days 4, 11, and 21, neuropathological evaluation and brain weights on days 11, 22, and 70, motor activity on days 13, 17, 21, and 70, passive avoidance on days 23 and 24, auditory startle habituation on days 23 and 60, or water maze testing on days 58-63. Pup physical development was assessed by bodyweight; sexual maturation was assessed by age at vaginal opening for females and age at completion of balano-preputial separation for males. No treatment-related effects were seen in the dams on survival, body weight, body weight gain, food consumption, clinical signs, or reproductive performances.
The maternal NOAEL is 0.60 mg/kg/day, the highest dose tested. The maternal LOAEL is not established.
Treatment had no adverse effects on the offspring survival, clinical signs, developmental landmarks, body weight, body weight gain, motor activity, auditory startle reflex, learning and memory, brain weights, brain morphology or neuropathology. During the period of direct dosing, 12 pups (5 males and 7 females) from 5 litters at the high dose exhibited tremors post-dosing only on Day 13.
The offspring LOAEL is 0.60 mg/kg/day, based on tremors observed on PND 13. The offspring NOAEL is 0.30 mg/kg/day.
This study is classified Acceptable/Non Guideline and may be used for regulatory purposes; however it does not satisfy the guideline requirement for a developmental neurotoxicity study in rats (OPPTS 870.6300, 83-6); OECD 426 (draft) at this time pending a comprehensive review of all available positive control data.
[Note - 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. J. Rowland, 09/26/2005]
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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; gavage; maternal GD 6 to PND 10;
offspring LD 11 to LD 21
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50608.0
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2005-09-26
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2010-11-16
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Added by
Madison Feshuk
on Apr 25, 2022
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