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43378101.der.pdf
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43378101
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Carbofuran
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1563-66-2
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090601
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Ponnock, K. (1994) A Developmental Neurotoxicity Study of Carbofuran in the Rat via Dietary Administration: Final Report: Lab Project Number: 93-4506: A93-3746. Unpublished study prepared by Pharmaco LSR, Inc. 557 p.
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1994.0
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Carbofuran: Groups of 24 impregnated Sprague-Dawley strain rats were fed diets containing 0, 20, 75, or 300 ppm (1.70-1.73, 4.95-6.91, or 8.57-31.38 mg/kg/day) technical Carbofuran from gestation day 6 and continuing through lactation day 10. Clinical signs and mortality were recorded daily and body weight and food consumption taken weekly throughout gestation and lactation.
Litters were observed daily for dead pups. Litters were culled to eight pups on Postnatal Day (PND) 4. Pinna detachment, incisor eruption, eye opening, vaginal patency, and preputial separation were evaluated for all surviving pups. Motor activity, auditory startle response and swimming, learning and memory evaluations were measured on one pup/sex/litter.
Other selected pups were sacrificed on PNDs 11 and 60, and body and brain weights were measured. Brain, spinal cord, sciatic nerve, and skeletal muscle tissues from 6/sex/group pups, which were sacrificed on PND 11 and 60, were also prepared for microscopic examination.
The maternal toxicity NOEL was 20 ppm. At the LEL of 75 ppm, there was decreased body weight gain and decreased food consumption during gestation days 6-10. During this same time, high dose females lost weight and had highly significantly decreased food consumption. The body weight of the high dose group was also significantly less than controls from gestation days 10-20.
The NOEL for developmental neurotoxicity was 20 ppm. At the LEL of 75 ppm and also at the high dose, there was increased pup mortality during the first 4 days of lactation which produced highly significantly decreased viability indices in comparison to controls (p < 0.01). Live birth indices were comparable between control and treated groups, and although the mid and high dose groups had lower weaning indices than controls, the differences were not statistically significant.
Pup body weight was highly significantly decreased at birth from 7- 16% and during the entire lactation period up to 25-38% in the mid and high dose groups (p < 0.01).
The NOEL for developmentally delayed parameters is 20 ppm and the LEL is 75 ppm with the effects being delay of vaginal patency and preputial separation.
Evaluations of auditory startle performed on PND 22 and 60±2 did not demonstrate any treatment-related effects at any treated dose in comparison to controls.
Evaluations performed on PND 13, 17, 22, and 60±2 did not demonstrate any treatment-related effects in motor activity. The NOEL for swimming angle development is 20 ppm.
Learning and memory were measured by water ¿Y¿ maze time trials performed on PND 24, 25, 30, 60, 61, and 65. The NOEL for learning and memory is the 20 ppm dose level.
There were no treatment-related effects in gross necropsy results in examined pups at day 11, 60, or post-day 60. There were no compound-related effects on absolute and relative brain weight directly attributable to carbofuran, or neurological histopathology of the brain, spinal cord, and peripheral nerves in Day 11 and Day 60 pups. Classification: Acceptable.
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Developmental-Neurotoxicity
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NA [83-6, Developmental Neurotoxicity]
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Oral
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No Duration Period; GD 6 to LD 10
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11792.0
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1996-02-12
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2018-04-12
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Kept file with cover memo that was previously cleared
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Added by
Madison Feshuk
on Apr 25, 2022
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