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46660601.der.pdf
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46660601
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Tetrachlorvinphos
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961-11-5
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083701
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Barnet Jr., J. (2005) Oral (Gavage) Developmental Neurotoxicity Study of Tetrachlorvinphos in Crl:CD (SD)IGS BR VAF/Plus Rats: Final Report. Project Number: 1608/003, PACA/DB04/04/633, PACA/DB04. Unpublished study prepared by Charles River Laboratories, Research Pathology Services and Consultants in Veterinary Pathology. 791 p.
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2005.0
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Tetrachlorvinphos: In a developmental neurotoxicity study (MRID 46660601), Tetrachlorvinphos (99.6% a.i.; Lot #: NJ250RB08) in aqueous 1% (w/v) methylcellulose was administered via gavage (10 mL/kg) to pregnant Sprague-Dawley rats (25/dose) from gestation day (GD) 6 to lactation day (LD) 6 at doses of 0, 10, 50, or 200 mg/kg/day. Additionally, the F1 pups were similarly dosed on postnatal days (PNDs) 7-21. Dams were allowed to deliver naturally and were sacrificed on LD 21. On PND 4, litters were standardized to 10 pups/litter; the remaining offspring and dams were sacrificed and subjected to a gross necropsy. Subsequently, 1 pup/sex/litter/group (at least 10 pups/sex/dose when available) were allocated to the following subsets: Subset 1, PND 21 brain weights and neurohistological evaluations; Subset 2, water maze and passive avoidance test; Subset 3, motor activity and auditory startle habituation; Subset 4, terminal brain weights and neurohistological evaluations; and Subset 5, standardize litter size to ten pups (5 male and 5 female) per litter on PND 4-21.
In dams, there were no treatment-related effects on mortality, clinical signs, body weight, body weight gain, feed consumption, FOB, or gross pathology. No treatment-related effects on reproductive parameters were observed. The maternal LOAEL was not observed. The maternal NOAEL was 200 mg/kg/day (HDT).
In offspring, there were no treatment-related effects on viability, litter observations, clinical signs, body weight, food consumption, FOB, motor activity, acoustic startle habituation, learning and memory (passive avoidance and water maze), gross pathology, or histopathology parameters. At 200 mg/kg/day, decreases (p¿0.05) in body weight were noted in the males (decr. 5-8%) on PNDs 15 and 16 (pre-weaning) and PND 22 (post-weaning) and in the females (decr. 6%) on PND 29 (post-weaning). Body weight gains were decreased (p¿0.05) during pre-weaning at several intervals in the males (decr. 12-28%) and females (decr. 13-26%). Decreases (p¿0.05) in body weight gains during post-weaning were observed in the males on PNDs 21-22 (decr. 36%) and in the females on PNDs 21-22 and 22-29 (decr. 7-28%). Absolute brain weight was decreased (p¿0.01) by 8% in the males. This finding was judged to correlate with the treatment-related decreases (p¿0.05) in several microscopic linear brain measurements: (i) thickness of the striatum on PND 21 (decr. 4-5% both sexes) and PND 70 (decr. 7% males only); (ii) thickness of the corpus callosum on PND 70 (decr. 16-21% both sexes); (iii) thickness of the hippocampal gyrus on PND 70 (decr. 7-9% both sexes); and (iv) height of the cerebellum on PND 70 (decr. 7% males only). It is noted that on PND 21, decrease in single morphometric parameter was seen in both sexes with the small magnitude (4-5%) whereas on PND 70, decrease in multiple morphometric measurements were seen in both sexes with greater magnitude (7-21%) than that seen in PND 21.
No treatment related effects were noted in the ¿50 mg/kg/day F1 offspring.
The offspring LOAEL was 200 mg/kg/day, based on decreases in body weight, body weight gains and several morphometric linear brain measurements in both sexes, and decreased absolute brain weight in the males on PND 70. The offspring NOAEL was 50 mg/kg/day.
This study is classified as 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 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 neurotoxiicity study and is classified as NonGuideline pending reeview of all positive control data. J. Rowland 03-19-2008]
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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; GD 6 to LD 6
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53833.0
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2008-03-19
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2008-04-07
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Added by
Madison Feshuk
on Apr 25, 2022
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