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50557201.der.pdf
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50557201
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Bensulide Oxon (degradate of bensulide)
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20243-81-6
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609801
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Barnett, J. (2018) Oral (Gavage) Repeat Dose Comparative Cholinesterase Study of Bensulide Oxon in Rat Pups and Adults. Project Number: 20129739, 20093189, 20090728. Unpublished study prepared by Charles River Laboratories. 205p.
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2018.0
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Bensulide oxon: In a non-guideline, repeat-dose cholinesterase study (MRID 50557201), groups of ten adult female Sprague-Dawley [Crl:CD(SD)] rats/dose level were administered Bensulide oxon (98.2% a.i., Lot #: GSO-008) in corn oil by daily oral gavage at nominal dose levels of 0, 15, 25, 50, and 75 mg/kg/day for ten days. In addition, groups of ten neonatal pups/sex/dose level were administered Bensulide oxon by daily oral gavage on post natal days (PND) 11-20 at nominal dose levels of 0, 10, 20, 40, and 60 mg/kg/day. Animals were euthanized at the presumed time of peak effect (16 hours for adults; 8 hours for pups) after the respective final dose administrations. Blood samples were collected prior to euthanasia, brains were excised and weighed, and samples were submitted for determination of red blood cell (RBC) and brain cholinesterase activity.
All adult females and all pups survived to scheduled euthanasia. No treatment related effects on clinical signs, body weights, overall body weight gains, or brain weights were observed for any adult female and pup treatment groups.
Dose-related decreases in mean RBC cholinesterase activity at the presumed peak time of effect (16 hours) were observed in all treated adult females at ≥50 mg/kg/day (↓32-52%). Dose-related decreases in mean brain cholinesterase activity at 16 h were observed only in the high-dose (75 mg/kg/day; ↓18%) females.
Dose-related decreases in mean RBC cholinesterase activity at the presumed peak time of effect (8 hours) were observed in the treated male and female pups at ≥10 mg/kg/day (↓21 75% and ↓20 71%, respectively); decreases were similar respective to dose in males and females. Dose related decreases in mean brain cholinesterase activity at 8 h were observed in the treated male and female pups at ≥20 mg/kg/day compared to control values (↓15-41% and ↓10-35%, respectively); decreases were similar to dose in males and females.
These data demonstrated that Bensulide oxon was a cholinesterase inhibitor in the rat, and that cholinesterase inhibition was observed at lower doses in rat pups compared to adult female rats (≥10 mg/kg/day pups vs. ≥50 mg/kg/day adult females for RBC cholinesterase and ≥20 mg/kg/day pups vs. 75 mg/kg/day adult females for brain cholinesterase).
This study is classified Acceptable/Nonguideline and provided data regarding the effects of oral gavage dosing of Bensulide oxon on brain and RBC cholinesterase inhibition in rat pups and adults.
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Other
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NA [00-0, Non-Guideline Study]
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Oral
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Treatment Duration: 10 Days;Repeat dose comparative cholinesterase study in rat pups and adults
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57800.0
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2019-03-06
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2019-03-08
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Added by
Madison Feshuk
on Apr 25, 2022
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