Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

Five male and five female F344/DuCrl rats per group were administered 0, 100, 300, or 1000 milligrams 6,6'-[[3,3',5,5'-tetrakis(1,1-dimethylethyl)-[1,1'- biphenyl]-2,2'-diyl] bis(oxy)]bis-dibenzo[d,f][1,3,2]-dioxaphosphepin per kilogram body weight per day (mg/kg/day) in corn oil via oral gavage for 28 days to evaluate the potential for systemic toxicity. Parameters evaluated were daily cage-side observations, daily clinical observations, weekly detailed clinical observations, ophthalmic examinations, functional tests, body weights, feed consumption, hematology, prothrombin time, urinalysis, clinical chemistry, selected organ weights, and gross and histopathologic examinations. There were no treatment-related effects in clinical signs, body weights, feed consumption, ophthalmic examinations, functional tests, hematology, prothrombin time, clinical chemistry, urinalysis parameters or gross pathologic observations. Treatment-related effects on organ weights were limited to statistically-identified higher absolute and relative liver weights of males and females in the 1000 mg/kg/day group, and a statisticallyidentified higher relative liver weight of males in the 300 mg/kg/day group. These organ weight findings corresponded to hepatocellular vacuolization (consistent with fatty change) of various regions of the liver lobules in males and females at these dose levels. All males in the 1000 mg/kg/day group had vacuolization of centrilobular/midzonal or panlobular hepatocytes consistent with a very slight or slight fatty change. Very slight fatty change in centrilobular hepatocytes was present in 2 of 5 males in the 300 mg/kg/day group. The majority of females in the 300 mg/kg/day (4 of 5 animals) and all of the females in the 1000 mg/kg/day group had periportal hepatocyte vacuolization consistent with a slight or moderate fatty change, respectively. The no-observed-effect level (NOEL) for F344/DuCrl rats of either sex was the targeted concentration of 100 mg/kg/day test material.

The no-observed-effect level (NOEL) for F344/DuCrl Rats of either sex was the targeted dose of 100 mg/kg/day test material. 

Justification for classification or non-classification