Evaluation of the immunotoxic potential of chlordecone with comparison to cyclophosphamide.
The immunotoxic potential of chlordecone was evaluated in male Fischer-344 rats following 10 d of acute dosing by oral gavage. These results were compared with those obtained following a comparable dosing regimen with the known immunosuppressive drug cyclophosphamide. Significant changes in ratios of spleen and thymus to body weight, blastogenic responsiveness of lymphocytes to concanavalin A, and natural killer (NK) cell activity against allogeneic W/Fu-G1 rat lymphoma target cells and xenogeneic YAC-1 mouse lymphoma target cells were observed only at the highest chlordecone dosage (10 mg/kg . d). A significant decrement in body weight also occurred at this dosage which suggests that the observed changes in the immune parameters measured were most likely due to the overt toxicity of chlordecone. In contrast, rats dosed over 10 d by oral gavage with cyclophosphamide showed significant decreases in spleen and thymus to body weight ratios at a dosage as low as 1.5 mg/kg . d. Body weight decrements were observed only at dosages of 12 mg/kg . d or greater. At dosages of 1.5 mg/kg . d or greater, cyclophosphamide caused a significant decrease in the total leukocyte and absolute lymphocyte counts in peripheral blood, and a decrease in the lymphoproliferative responses to both T- and B-lymphocyte mitogens. Significant suppression of NK cell activity was observed at dosages of 6 mg/kg . d or greater. These results suggest that T and B lymphocytes are more sensitive than are NK lymphocytes to the immunosuppressive effects of cyclophosphamide. The results of these two studies indicate that the failure to detect chlordecone-induced immunotoxic effects in the absence of overt toxicity is not due to the possible insensitivity of the parameters examined. Instead, since cyclophosphamide affected all of the parameters tested, these results indicate that the endpoints examined here are capable of detecting immunotoxicity with sufficient sensitivity to permit distinction between probable indirect immunosuppression due to overt toxicity and subtle, direct impairment of the immune system.
Smialowicz
R J
RJ
Luebke
R W
RW
Riddle
M M
MM
Rogers
R R
RR
Rowe
D G
DG
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D007631:Chlordecone / Q000633:toxicity*; D003520:Cyclophosphamide / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007109:Immunity / Q000187:drug effects*; D007306:Insecticides / Q000633:toxicity*; D007958:Leukocyte Count / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects
D007306:Insecticides; D003520:Cyclophosphamide; D007631:Chlordecone