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48709905.der.pdf
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48709905
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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: Repeat Dose Comparative Sensitivity Study in Young Adult Female and 11 Day Old Neonatal CD Rats by Oral Gavage Administration: Final Report. Project Number: BDG0030, 710/NEU/024. Unpublished study prepared by Huntingdon Life Sciences, Ltd. 100p.
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2011.0
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Tribufos: In a repeat dose comparative sensitivity study (2011, MRID 48709905) in Crl:CD(SD) strain rats by gavage administration, tribufos (98.2% a.i., Batch # NX8 JAX0015) was administered at dose levels of 0, 0.1, 1.0 or 5.0 mg/kg bw/day to 8 young adult females/group and 8 male and 8 female neonatal pups (11 days old)/group. The animals were dosed at 5 mL/kg corn oil for 11 consecutive days. Clinical signs of toxicity, mortality, body weights, cholinesterase (ChE) measurements [erythrocyte (RBC) and brain determinations], brain weights and macroscopic pathology data were obtained.
Systemic Effects. In adults, salivation was noted in 1 female in the 1.0 and one in the 5.0 mg/kg/day 1-2 h after dosing. However, salivation was not reported as an adverse effect in the subchronic neurotoxicity study (2001, MRID No.: 45369101) at dietary doses up to 4.6 mg/kg/day. No other effects were noted in the adult females. In pups, reactions were noted at 5 mg/kg/day 1-2 hours postdosing including four males and 5 females with unsteady muscle reaction and one male and five females with prostrate posture as well as under activity. At terminal sacrifice, male body weight was statistically significantly (p<0.05) decreased by 8 % in the 5.0 mg/kg/day group. Female pup body weight at termination was statistically significantly (p<0.05) decreased by 9, 5, and 9 % (p<0.01), in the 0.1, 1.0 and 5.0 mg/kg/day group, respectively. Body weight gain was slightly, but statistically significantly lower (p<0.05) in female pups receiving 0.1, 1.0 and 5.0 mg/kg/day by 10, 6 and 9 %, respectively, from day of treatment 1-11. There was, however, no dose response to allow for a firm conclusion that body weight was affected in female pups. At best there is a slight change in body weight in the pups. The LOAEL for systemic toxicity in young adult females was not established. The NOAEL is > 5 mg/kg/day. The LOAEL for systemic toxicity in pups is 5 mg/kg/day based on unsteady muscle reaction, prostrate appearance and underactivity. The NOAEL is 1 mg/kg/day.
ChE Inhibition. RBC ChE was statistically significantly inhibited in adults in the 1.0 and 5.0 mg/kg/day group by 18% (p < 0.05) and 64 %, respectively. RBC ChE was statistically significantly inhibited only in the 5.0 mg/kg/day group by 66% in males and 69 % in females. Thus, the adults are more sensitive than the pups to inhibition of RBC ChE by tribufos.
Brain ChE. Brain ChE was not inhibited in adults. Brain ChE was statistically significantly inhibited in the 5.0 mg/kg/day group by 20% in males and 21% in females. Thus, the pups are more sensitive than the adults to the inhibition of brain ChE by tribufos.
The LOAEL for RBC ChE inhibition is 1.0 mg/kg bw/day in young adult females. The NOAEL is 0.1 mg/kg bw/day. The LOAEL for adult brain ChE inhibition is > 5 mg/kg/day. The NOAEL was not established.
The LOAEL for male and female pup RBC and brain ChE inhibition is 5.0 mg/kg bw/day. The NOAEL is 1.0 mg/kg bw/day.
Classification. This repeat dose comparative sensitivity study in young adult female and 11 day old neonatal CD rats is acceptable (non-guideline).
NOTE: The conclusions in this DER are based on the NOAEL and LOAELs and the extent of inhibition at the LOAEL and at higher doses. The points of departure may differ pending application of benchmark dose modeling.
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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; Repeat 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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