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46740201.de.pdf
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46740201
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Chlorfenapyr
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122453-73-0
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129093
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Schneider, S.; Kaufmann, W.; van Ravenzwaay, B. (2006) BAS 306 I: Developmental Neurotoxicity Study in Wistar Rats: Oral Administration to the Dams and Pups (Gavage). Project Number: 66R0346/03066, 2006/1002523, 03066. Unpublished study prepared by BASF Aktiengesellschaft, Experimental Toxicology and Ecology. 994 p.
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2006.0
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Chlorfenapyr: In a developmental neurotoxicity study (MRID 46740201) BAS 306 I [Chlorfenapyr (97.8%, batch 2181H88HV)] was administered by gavage to 40 female Wistar rats per dose at 0, 5, 10 or 15 mg/kg bw/day from gestation day (GD) 6 through lactation day (LD)10. A Functional Observational Battery (FOB) was performed on 10 dams per group on GDs 7 and 14 and LDs 7 and 14. On postnatal day (PND) 4, litters were culled to yield four males and four females (as closely as possible). The test material was administered by gavage at the same dose levels to pups from PND 11 through PND 21. Offspring were allocated for detailed clinical observations (FOB) and assessment of motor activity, auditory startle reflex habituation, learning and memory (water maze testing) and neuropathology at termination (PND 62). On PND 22, the whole brain was collected from 10 pups/sex/group for histopathologic examination and morphometric analysis. Pup physical development was evaluated by body weight. The age of sexual maturation (vaginal opening in females and preputial separation in males) was assessed.
No deaths or clinical signs of toxicity were reported in dams during gestation or lactation. Body weight and food consumption were not affected by treatment. Gross necropsy of dams was unremarkable and brain weight and morphometry were similar between treated and control groups.
Pregnancy rate, gestation length, the mean number of delivered pups per dam and percentage of liveborn and stillborn pups were not affected by treatment. Pup deaths (including cannibalization) increased in the mid- and high-dose groups during PND 1-4 on an individual and litter basis.
Among surviving pups, no treatment-related effects on sex ratio, clinical signs, pre- and post-weaning body weight, FOB observations, acoustic startle response or learning and memory in offspring were observed. The mean day of achieving sexual maturation in treated animals was comparable to the control group. A dose-related decrease in total movement on PND 13 was observed in treated males and females. The decrease (53% of control value) was significant at 15 mg/kg/day. During the PND 13 sub-session, the distance moved was generally lower in males and females at 10 and15 mg/kg/day, but the change was significant for only one sub-session in each sex. No treatment-related effects on total distance moved on PNDs 17, 21 or 60 or on the total number of rearings at any of the testing periods were observed
Brain weight and measurement of the cerebrum and cerebellum were comparable between treated and control groups on PNDs 22, 62 and 111. On microscopic examination at PND 22, treatment-related minimal to moderate vacuolation of the white matter was observed in several areas of the brain, including the frontal lobe, parietal lobe, midbrain, pons, cerebellum and medulla oblongata, in up to 4/10 males and 4/10 females in the high-dose group compared to none in the control group. The low- and mid-dose groups were examined and no lesions were observed. No treatment-related microscopic findings were observed at the PND 62 necropsy. On morphometric examination, size of the left and right hippocampus in females at 15 mg/kg/day was significantly decreased on PND 62. Dimensions of these tissues in females at 5 and 10 mg/kg/day were comparable to the control group.
The maternal LOAEL was not established and the maternal NOAEL is 15 mg/kg/day.
The offspring LOAEL is 10 mg/kg/day, based on pup deaths (PND 1-4) and decreased motor activity in males and females on PND 13. The offspring NOAEL is 5 mg/kg/day. Vacuolation of white matter in the brain and decreased hippocampus size were also observed in offspring at the high dose (15 mg/kg/day).
This study is classified as Acceptable/Guideline and satisfies the guideline requirement for a developmental neurotoxicity study in rats (OPPTS 870.6300; §83-6; OECD 426 (draft)). Although, there is no LOAEL observed in dams, the study is acceptable since effects were seen in offspring.
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Developmental-Neurotoxicity
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NA [83-6, Developmental Neurotoxicity|870.6300, Developmental neurotoxicity study]
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Oral
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No Duration Period; (gavage) treatment lasted from GD 6 through LD 10; positive control MRID 46210605
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56892.0
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2014-02-18
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2019-11-14
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Supplemental #1
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Added by
Madison Feshuk
on Apr 25, 2022
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