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45902304.DER.pdf
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45902304
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Topramezone
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210631-68-8
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123009
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Kaufmann, W.; Schneider, S.; van Ravenzwaay, B. (2003) BAS 670 H--Developmental Neurotoxicity Study in Wistar Rats Asministration (sic) in the Diet: Final Report: Lab Project Number: 67R0124/98140: 2003/1006263. Unpublished study prepared by BASF Aktiengesellschaft. 712 p. {OPPTS 870.6300}
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2003.0
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Topramezone: In a developmental neurotoxicity study (MRID 45902304), BAS 670H (95.8% a.i.; Batch/Lot #: N26) was administered in the diet to pregnant Wistar rats (38-39/dose) from gestation day (GD) 6 to postnatal day (PND) 21 at nominal doses of 0, 8, 80, or 800 mg/kg/day (actual doses were 0/0, 8.2/6.7, 83.7/69.6, and 848.6/739.1 mg/kg/day [gestation/lactation]). Dams were allowed to deliver naturally and were killed on lactation day (LD) 21. On PND 4, at least twenty-two litters of appropriate size (>= 8 pups/litter) were available. These litters were standardized to 8 pups/litter; the remaining offspring and dams were sacrificed and discarded without further examinations. Subsequently, 10 pups/sex/group were allocated to Subsets 1-6 for neurobehavioral testing and neuropathological examination.
No treatment-related effects were observed in the dams on survival. There were transient decreases in body weight, body weight gain and food consumption at the mid (80 mg/kg/day) and high dose (800 mg/kg/day) dams during gestation and/or lactation. Corneal opacities in females were considered a treatment-related effect at all doses. The incidences were: 4/34, 22/35 and 12/32 at the low, mid and high dose groups, respectively compared to 0/35 in the controls.
The maternal LOAEL is 8 mg/kg/day based on corneal opacities. A maternal NOAEL was not established.
Treatment-related effects seen at the mid and high dose groups include decreases in body weight and bodyweight gain in both sexes, and delayed preputial separation in males. Treatment had no adverse effects on offspring survival, clinical signs, FOB, motor activity, or learning and memory. Treatment-related effects were seen in the auditory startle response in both sexes on PND 24 at all dose levels. For males, maximum auditory startle response amplitude was decreased 30%, 27%, and 38% on PND 24 at 8, 80, and 800 mg/kg/day, respectively. For females, maximum auditory startle response amplitude was decreased 22%, 34%, and 54% on PND 24 at 8, 80, or 800 mg/kg/day, respectively. No significant differences from control were noted in startle response maximum amplitude at any dose in either sex on PND 60. Treatment-related decreases in absolute brain weights were seen in males on PND 62 and in females on PND 22 at all doses. Changes in the various regions of the brain were observed in pups of both sexes at all dose levels at PND 22 and PND 62.
The offspring LOAEL is 8 mg/kg/day, based on decreased maximum auditory startle reflex response, decreased brain weights and changes in the brain morphology. The offspring NOAEL was not established.
This study is classified Acceptable 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, 09/29/2005.]
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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 PND 21
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52097.0
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2005-09-29
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2020-09-14
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Added by
Madison Feshuk
on Apr 25, 2022
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