Groups of 93 male and 93 female Sprague-Dawley rats were fed diets containing 1, 5, 25, and 250 ppm fenvalerate for up to 2 yr. The control group consisted of 183 males and 183 females. Approximately 10 treatment and 20 control rats/sex . group were killed at intervals of 3, 6, 12, and 18 mo. When body weights, food consumption, hematology, clinical chemistry and organ weights did not reveal a treatment effect, two additional groups of 50 males and 50 female rats were placed on 0 or 1000 ppm fenvalerate diets and maintained for 2 yr. Body weight was decreased and organ/body weight ratios were increased in brain, liver, spleen, kidneys (females), heart (females), and testes (males) in the 1000 ppm group. Mammary and pituitary tumors were commonly observed, along with a variety of other tumors occurring randomly among all control and treatment groups. No statistically significant differences in the number and type of neoplasms were observed except for mammary tumors in females in the main study. These effects were judged not to be toxicologically significant, since mammary tumor incidences did not exceed expected incidences in aged female Sprague-Dawley rats, time to tumor appearance was unchanged, and no shift in percent benign versus malignant tumors occurred. Sarcomas identified in the subcutis and dermis in 5/51 1000-ppm-treated males were also identified in 2% (1/50), 2% (2/102), and 0-6% of concurrent, original, and historical controls, respectively. Microscopic examination did not reveal any treatment-related lesions. The no-observable-effect level was determined to be 250 ppm.

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Reports of neurologic impairment of children following recovery from acute lead encephalopathy have raised questions concerning the effects of chronic low-level lead exposure on the central nervous system. Behavioral toxicologic techniques have been employed to assess the effects of lead on the central nervous system in sheep. Mature sheep receiving daily doses of 100 mg lead/kg showed a significant decrease in performance on an auditory signal detection task. Daily oral doses of 120 and 230 mg lead/sheep for 27 weeks did not alter the performance of mature sheep on a fixed-interval schedule of reinforcement behavioral task. Prenatal exposure to maternal blood lead levels of 16 or 34 mug/100 ml during gestation and postnatal daily ingestion of 16, 8, 4, or 2 mg lead/kg did not alter performance of lambs on a closed-field maze task. Slowed learning was demonstrated in lambs prenatally exposed to maternal blood lead levels of 34 mug/100 ml during gestation when tested on nonspatial, two-choice visual discrimination problems at 10-15 months of age.

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