Effects of toxaphene on the immune system of cynomolgus (Macaca fascicularis) monkeys.
Toxaphene, dissolved in glycerol/corn oil, was administered at 0.1, 0.4 or 0.8 mg/kg body weight/day in gelatin capsules to groups of 10 young adult female cynomolgus monkeys (Macaca fascicularis), while a group of five male monkeys (Macaca fascicularis) received 0.8 mg/kg body weight/day. Control male (a group of five) and female (a group of 10) monkeys ingested the glycerol/corn oil vehicle only. Treatment continued for 75 weeks. Testing for immune effects was initiated at 33 weeks of treatment. Immunization was initiated at 44 weeks of treatment. Pairwise comparisons between each of the treated female groups to the control indicated that the mean primary (post-immunization weeks 1-4) and secondary (post-immunization weeks 5-8) anti-SRBC IgM responses were significantly reduced at the 0.4 and 0.8 mg/kg body weight/day doses compared to the control (P< or =0.05). The mean primary (post-immunization weeks 1-4) anti-SRBC IgG response was significantly reduced compared to the control (P< or =0.05), while the secondary (post-immunization weeks 5-8) anti-SRBC IgG was not significantly affected by treatment (P>0.05). The mean anti-tetanus toxoid IgG response in the 0.8 mg/kg body weight/day dose group The mean primary anti-SRBC (IgM) response in the treated males was significantly different from the control (P<0.05), while the primary anti-SRBC IgG response was not affected by treatment. The mean absolute B-lymphocyte numbers in the female group administered 0.8 mg/kg of toxaphene was significantly reduced compared to the control (P< or =0.05). All other parameters including the natural killer cell activity, the delayed-type hypersensitivity response, the lymphoproliferative response of peripheral blood leukocytes to the mitogens Con A and PWM and the serum cortisol levels were not affected significantly by treatment (P>0.05). The no-observed-adverse-effect level (NOAEL) for the female monkeys based on the toxaphene effects on humoral immunity was 0.1 mg/kg body weight/day.
Tryphonas
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H
Toxicology Research Division, PL2202D1, Bureau of Chemical Safety, Health Products and Food Branch, Health Canada, Ottawa, KA1 0L2, Ontario, Canada. helen_tryphonas@hc-sg.gc.ca
Arnold
D L
DL
Bryce
F
F
Huang
J
J
Hodgen
M
M
Ladouceur
D T
DT
Fernie
S
S
Lepage-Parenteau
M
M
Hayward
S
S
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006968:Hypersensitivity, Delayed; D007107:Immune System / Q000187:drug effects*; D007108:Immune Tolerance; D007111:Immunity, Cellular / Q000187:drug effects*; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood* / Q000276:immunology; D007306:Insecticides / Q000276:immunology / Q000633:toxicity*; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D014112:Toxaphene / Q000276:immunology / Q000633:toxicity*
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007306:Insecticides; D014112:Toxaphene