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46484603.der.pdf
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46484603
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Di-isopropyl fluorophosphate and D-Amphetamine
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55-91-4|51-64-9
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356100|600005
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Myers, D. (2005) Validation of Functional Observation Battery for Pre-Weaning Rat Pups in Developmental Neurotoxicity Screening. Project Number: HLS/088/993755.Unpublished study prepared by Huntingdon Life Sciences Ltd. 62 p.
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2005.0
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D-Amphetamine and Di-isofluoro-phosphate: This Functional Observational Battery (FOB) (MRID 46484603) was conducted on groups of 10 Crl:CD® (SD) IGS BR rats/sex/dose. On PND 4 and 11, animals were observed in the open arena 30 minutes after oral administration of saline (vehicle control), 3 mg di-isofluoro-phosphate/kg/day [this is probably di-isopropyl-fluorophosphate] or 2 mg D-amphetamine/kg/day. An untreated control group was also included. On both days, the animals were tested for surface righting reflex. On PND 4 maximum pivoting angle, maximum distance traveled, and activity counts were measured. On PND 11 grooming score, activity and rearing counts, and urination were recorded. The duration of the open field observation was 1 minute.
Two males treated with di-isofluoro-phosphate on PND 4 were found dead on PND 5; deaths were attributed to treatment with the maximum tolerated dose. These animals were replaced by siblings for PND 11 testing. All remaining offspring survived to scheduled sacrifice. No significant treatment-related effects on body weight or body weight gain were observed for males or females treated with either substance. Offspring treated with D-amphetamine on PND 4 had slightly reduced (86-90% of control level) weight gain during PNDs 4-7 compared with the vehicle control group. However, weight gain was comparable for all groups during PNDs 7-11.
During the FOB, no changes in appearance, condition, or behavior were noted in any treated group on either testing day. For PND 4 pups treated with di-isofluoro-phosphate, maximum pivoting angle tended to be decreased in males and females although the controls were highly variable. The surface righting reflex score was slightly improved for both sexes on PND 4 with statistical significance (p ¿ 0.05) attained for females. No treatment-related effects were noted on PND 11. Following treatment with D-amphetamine on PND 4, the maximum pivoting angle, distance traveled, and activity were increased in females and on PND 11, activity and rearing were increased in both sexes with statistical significance (p ¿ 0.05) attained for activity in males.
This study is classified Acceptable/Nonguideline. Huntingdon Life Sciences, Ltd. has demonstrated proficiency in this study for detecting changes in FOB due to D-amphetamine and Di-iosfluoro-phosphate treatments in preweaning (PND 4, 11) Crl:CD® (SD)IGS BR rat pups for the time period around 1999 (in life period of study). This positive control study does not satisfy any guideline requirement.
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Other
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NA [870.6300, Developmental neurotoxicity study]
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Oral
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No Duration Period; Neurobehavioral (functional observational battery) positive control data
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53777.0
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2012-03-20
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2016-09-07
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Added by
Madison Feshuk
on Apr 25, 2022
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