(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

The toxicity of benzene to natural killer cells (NK cells) involved in non-specific host resistance,
and on interleukin-2, an important growth factor for T, B, and NK cells and in regulation of
granulocyte and eosinophil production, was examined by Fan (1992). Male C57Bl/6 mice were
exposed to benzene in drinking water at concentrations of 0, 152, or 853 mg/L (0, 27, or
154 mg/kg/day) for 7–28 days, with sacrifices at 7, 14, 21, or 28 days of exposure. A separate
group was exposed to 152 mg/L (27 mg/kg/day) for 28 days, and sacraficed at 7, 14, or 21 days
after the last dose. No overt signs of toxicity were seen, but significant decreases in number of
spleen cells were observed after 21 days of exposure at 27 mg/kg, and after 14 days at
154 mg/kg. After 21 days, a significant increase in spleen NK cell activity was observed at both
doses, but this activity was not present after 28 days in either group. Spleen cell numbers and
interleukin-2 production were depressed in mice given 27 mg/kg for 28 days, and 7 and 14
(interleukin-2 only) days after exposure. The LOAEL was determined to be 27 mg/kg/day
(152 mg/L), the lowest dose tested. White et al. (1984) exposed female B6C3F1 mice to
benzene in drinking water (containing emulphor to increase the solubility of benzene) at higher
concentrations of 0, 50, 1000, or 2000 mg/L (0, 12, 195, or 350 mg/kg/day) for 30 days. Body
weight was significantly decreased (p