Effects of short-term oral combined exposure to environmental immunotoxic chemicals in mice

Abstract

People are constantly exposed to environmental chemicals through contact with the atmosphere or by ingestion of food. Therefore, when conducting safety assessments, the immunotoxic effects of combinations of chemicals in addition to toxicities produced by each chemical alone should be considered. The objective of the studies reported here were to demonstrate the combined effects of three well-known environmental immunotoxic chemicals -- methoxychlor (MXC), an organochlorine compound; parathion (PARA), an organophosphate compound; and piperonyl butoxide (PBO), an agricultural insecticide synergist -- by using a short-term oral exposure method. Seven-week-old Balb/cAnN mice received daily oral exposure to either one or two of the environmental immunotoxic chemicals for 5 consecutive days. On Day 2, all mice in each group were immunized with sheep red blood cells (SRBC), and their SRBC-specific IgM responses were analyzed by using an enzyme-linked immunosorbent assay and plaque-forming cell assay. T- and B-cell counts in the mouse spleens were also assessed via surface antigen expression. Mice that received MXC + PARA and PBO + MXC treatment showed marked decreases in SRBC-specific IgM production and T- and B-cell counts compared with those in mice that received vehicle control or the corresponding individual test substance. This suggests that simultaneous exposure to multiple environmental chemicals increases the immunotoxic effects of the chemicals compared to individual exposure.

• Acquired immunotoxicity
• combined toxicity
• methoxychlor
• parathion
• piperonyl butoxide

Acknowledgements

This work was supported by a research Grant-in-Aid from the Ministry of Health, Labor, and Welfare of Japan. The authors wish to thank Mrs Y. Tajima and L. Miyashita of the Institute of Environmental Toxicology (Ibaraki, Japan) for their technical assistance.