(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

Oral
In a 1979 meeting abstract, Nawrot and Staples reported that benzene administered at doses of
0.3, 0.5, and 1.0 mL/kg to CD-1 mice on GDs 6–15 produced maternal lethality, increased
embryonic lethality at 0.5 and 1.0 mL, and significantly decreased fetal body weight at all three
doses. No malformations were seen. Exposure of pregnant Sprague Dawley rats to benzene
orally by gavage at doses of 0, 50, 250, 500, and 1000 mg/kg/day on GDs 6–15 resulted in
decreased food consumption, decreased maternal body weight, and body-weight gain at 500
and 1000 mg/kg/day, and increased incidence of alopecia at 1000 mg/kg/day. Developmental
toxicity was limited to decreased fetal body weight at 500 and 1000 mg/kg/day; no external
malformations were observed, and skeletal and soft-tissue evaluations were not performed
(Exxon Chemical Co., 1986). Using the Chernoff/Kafloff screening procedure, Seidenberg et al.
(1986) demonstrated that benzene, administered orally at 1300 mg/kg/day to ICR/SIM mice on
GDs 8–12, had no effect on maternal body weight but did produce significantly lower neonatal
body weight on days 1 and 2 after birth.
Exposure of mice and rabbits to benzene induced developmental effects similar to those seen in
rats. CF-1 mice exposed to 0 or 500 ppm (1597 mg/m 3 ), 7 hours/day, on GDs 6–15, with
sacrifice on GD 18, produced fetuses with decreased body weight and significantly increased
skeletal variants but no malformations in the absence of maternal toxicity. New Zealand White
(NZW) rabbits exposed to the same concentrations on GDs 6–18, with sacrifice on GD29,
produced fetuses with statistically significant decreases in minor skeletal variants (lumbar spurs
and increased proportion of fetuses with 13 ribs) and no maternal toxicity (Murray et al., 1979).
Ungváry and Tátrai (1985) exposed CFLP mice and NZW rabbits to 0, 156, and 313 ppm (0,
498, and 1000 mg/m 3 ) benzene, 24 hours/day on GDs 6–15 (mice) and GDs 7–20 (rabbits).
Moderate concentration-dependent maternal toxicity was reported in mice, and fetuses showed
weight and skeletal retardation at both concentrations (p