Assessment of the immunotoxic potential of the fungicide dinocap in mice.
The immunotoxic potential of dinocap was evaluated in female C57BL/6J mice following in vivo and in vitro exposure to this fungicide. In in vivo studies, groups of mice were dosed by gavage with technical grade dinocap at dosages ranging from 12.5 to 50 mg/kg per day for 7 or 12 days and selected immune functions examined. Mice dosed at 50 mg/kg per day dinocap died after 4 days of dosing. Twelve days of dosing with dinocap at 25 mg/kg per day resulted in decreased thymus weights and cellularity, and increased spleen weights. No changes were observed in body weight, absolute differential peripheral leukocyte counts, the lymphoproliferative responses to B- or T-cell mitogens, the mixed lymphocyte reaction, or natural killer (NK) cell activity of spleen cells from mice exposed to dinocap. Lymphoproliferative responses to concanavalin A (Con A) and phytohemagglutinin (PHA), however, were reduced in thymocytes from mice dosed at 25 mg/kg per day dinocap. The cytotoxic T lymphocyte (CTL) response to P815 mastocytoma cells was enhanced in mice exposed for 7 days to 25 mg/kg per day dinocap. Exposure of mice for 7 days to 25 mg/kg per day dinocap also caused a significant reduction in the IgM and IgG plaque-forming cell (PFC) response to sheep red blood cells (SRBC). A time-course study indicated that dinocap-induced suppression of the IgM PFC response was due to a delay in the peak PFC response to SRBC. In vitro studies using murine thymocytes cultured with dinocap (10 micrograms/ml for 72 h) resulted in suppression of the proliferative response to Con A and PHA. Exposure of thymocytes to dinocap in vitro for as little as 30 min resulted in suppression of the mitogen-stimulated response in the absence of any apparent direct cytotoxic effect. These results suggest that dinocap alters the immune system of the mouse, however, these effects are relatively modest in terms of adverse immune function and are only seen at relatively high exposure levels.
Smialowicz
R J
RJ
Health Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Luebke
R W
RW
Riddle
M M
MM
D000284:Administration, Oral; D000818:Animals; D004136:Dinitrobenzenes / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005659:Fungicides, Industrial / Q000008:administration & dosage / Q000633:toxicity*; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D066298:In Vitro Techniques; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects
D004136:Dinitrobenzenes; D005659:Fungicides, Industrial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C007500:dinocap