For exposure-response array data display purposes, the following results were coded (control and no effect findings were coded as "0", treatment-related increases were coded as "1", and treatment-related decreases were coded as "-1"

This endpoint should have been included in the reproductive summary, but was not so it is included here.

"Based on the results of this study, systemic toxicity was manifested at a dosage level of 75 (effects on body weight and body weight gain only) and 225 mg/kg/day (as evidenced by the following). Mortalities, changes in the clinical condition of the animals, effects on body weight, food consumption, serum chemistry (higher mean albumin, total protein, globulin, potassium, urea nitrogen, creatinine, bilirubin, alanine aminotransferase and aspartate aminotransferase levels and lower mean sodium and chloride levels), macroscopic findings (consisting of pale kidneys: males and small spleen: females), organ weights (higher mean liver and kidney weights) and microscopic changes (kidneys, pancreas, sternal bone marrow and lymphoid tissues, liver, adrenal cortex, jejunum and ileum). Dystocia was noted at the 225 mg/kg/day dosage level. Therefore, a dosage level of 75 mg/kg/day was considered to be the marginal lowest-observed-effect level (LOEL) for systemic toxicity. The NOEL for systemic toxicity was 25 mg/kg/day."

Note: dystocia is a perturbation in the normal progression of labor, so this effect would have been observed just in females. The study report does not provide any information related to gestation or delivery, and also does not give any indication that female animals were pregnant.

Crl:CD(SD) Female Rats