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48709904.der.pdf
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48709904
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Tribufos
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78-48-8
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074801
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Leggett, A. (2011) Tribufos: Single Dose Comparative Sensitivity Study in Young Adult Female and 11 Day Old Neonatal CD Rats by Oral Gavage Administration: Final Report. Project Number: BDG0029, 710/NEU/023. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 86p.
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2011.0
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Tribufos: In a comparative cholinesterase inhibition study (2011, MRID 48709904)in rats ((Sprague-Dawley Crl:CD (SD)), groups of 8 young adult (female only, aged 48-52 days) and pups (11 days old male and female) were administered Tribufos (98.2% a.i., batch # NX81AX0015) in corn oil at doses of 0, 2, 10 or 50 (pups only) or 80 (adults only) mg/kg bw. Clinical observations were made prior to dosing and at 3 and 6 hours and 24 (adults only). RBC and brain cholinesterase (ChE), brain weights and gross pathology were determined at times of sacrifice or at 6 hours for the pups and 24 hours for the adults.
Behavioral and systemic reactions. Clinical signs were not noted in adult females. The 10 mg/kg neonates exhibited under activity at 6 hours post dosing and at 50 mg/kg under activity and uncoordinated gait was noted as early as 3 hours and signs of being unsteady at 6 hours. There were no effects on mortality, brain weight, or gross pathology. Body weights of male and female pups were slightly lower (males 6.7 to 11% and females 7.3 to 8.9%) for all doses without a dose response and were not definitely related to treatment and will not be considered in the LOAEL statement.
The LOAEL for systemic effects in pups is 10 mg/kg based on under activity. The NOAEL for pups is 2 mg/kg. The LOAEL for systemic effects in adults was not established since no effects were noted. The NOAEL is > 80 mg/kg. Pups are more sensitive than adults. The lower body weights were noted but not definitely related to treatment.
ChE Inhibition. RBC ChE. After 6 hours, RBC ChE was inhibited to 27% (p < 0.05), 33% and 89% for the 2, 10 and 50 mg/kg female pups dose groups, respectively. In male pups, inhibition reacted 47% and 86% for the 10 and 50 mg/kg dose groups. In female adults there was 74% inhibition at 24 hours in the 80 mg/kg dose group only.
Brain ChE. Brain ChE was inhibited in the pups by 19% in males and 16% in females (p < 0.01) at 10 mg/kg and 75-76% in both sexes at 50 mg/kg. Adult female brain ChE was inhibited to only 11% (p < 0.01) at 80 mg/kg.
The LOAEL for RBC ChE in pups is < 2 mg/kg based on 27% inhibition (p < 0.05) in females. The NOAEL was not established. The LOAEL for brain ChE inhibition in pups is 10 mg/kg based on 16-19% inhibition (p < 0.01) in both sexes. The NOAEL is 2 mg/kg/day.
The LOAEL for adults for both RBC and brain ChE inhibition is 80 mg/kg. The NOAEL is 10 mg/kg.
Conclusion: Pups are more sensitive to the inhibitory effects of tribufos than adults.
Classification: This non-guideline comparative cholinesterase study is classified as Acceptable/Non-Guideline and established that pups are more sensitive to both systemic and ChE inhibitory effects of tribufos. A study deficiency is that plasma ChE was not assessed for.
Note: The conclusions are based on the NOAELs and LOAELS and the degree of effect at the dose levels tested. Additional assessment using benchmark dose modeling may render other points of departure and further refine the sensitivity issues.
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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; Single dose comparative ChE in 11 day old pups & young adults
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56274.0
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2012-08-09
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2019-06-04
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Added by
Madison Feshuk
on Apr 25, 2022
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