Immunotoxicity study of repeated small doses of dimethoate and methylparathion administered to rats over three generations

Abstract

<jats:p> Immunotoxic effects of chronic, equitoxic doses (1/50, 1/75, and 1/100 LD50) of two organophosphorus pesticides dimethoate (DM) and methylparathion (MPT) (14.1, 9.39, and 7.04 mg kg<jats:sup>-1</jats:sup> DM; and 0.436, 0.291, and 0.218 mg kg<jats:sup>-1</jats:sup> MPT) were investigated in a three generation study in out- bred Wistar rats. Treatment of the first generation (G1) with these doses began in animals 4 weeks of age; the parental males were dosed until separation of females, and after mating the females were treated until separation of their G2 offspring (at the age of 4 weeks), and the G3 generation was produced in the same way from treated parental G2 animals. Selected 4 week old males from each generation were also treated with DM and MPT for 4 weeks (experimental groups) before determination of certain conventional toxicological (body weight gain, birth weight and number, organ weights), haematological (absolute and differential WBC, RBC, Ht, MCV, nucleated cell content of femoral bone marrow), and immune func tion parameters (IgM-PFC number of spleen, DTH reac tion). </jats:p><jats:p> Effects of both substances on immunological variables were detectable at the 1/75 LD50 dose level, but different parameters were affected in the three consecutive genera tions. </jats:p>

Lymphoma risk and occupational exposure to pesticides: results of the Epilymph study

“…The lack of consistent dose response trends with all the exposure metrics might support chance as the explanation for the observed associations, or it might imply some mechanism different from a direct intervention in the carcinogenic process. For instance, dimethoate was shown to have the lowest cytotoxic and genotoxic potential in cultured cells, compared to other three organophosphates and the organochlorine endosulfan;80 however, its administration in experimental female mice caused a decrease in total immunoglobulins and IgM and in the number of plaque forming cells;81 the same effects were observed over three generations following repeated administration of low doses dimethoate in outbred Wistar rats 82. Functional activity of Th1 lymphocytes, immune reactions associated with these cells, and interferon- γ  production were impaired after subacute malathion intoxication in albino rats,83 while thymic atrophy and reduction in splenic germinal centres followed methylparathion administration in rabbits 84.…”

The Organophosphate Paraoxon Has No Demonstrable Effect on the Murine Immune System following Subchronic Low Dose Exposure

“…Particularly unclear is the issue of the effect of OPs on the immune system. Numerous publications report on various changes in immunologic parameters subsequent to OP exposure, including changes in thymus and spleen weights (7)(8), reduction in the number and/or function ofB and T lymphocytes (9)(10), and decrease in host resistance to pathogens (11). Despite some recent excellent reviews on the topic (12), what remains unclear is whether the reported changes are the consequence of esterase inhibition and, as such, a class effect of OPs or the result of compound-specific effects unrelated to esterase inhibition, or a combination of the above.…”

Immunotoxicological examination of repeated dose combined exposure by dimethoate and two heavy metals in rats

“…The 14.1 mg/kg dose signi®cantly decreased the PFC content of the spleen in the ®rst generation but had no effect on DTH reaction. 7 Because of this, a higher dose (28.2 mg/kg=1/50 LD 50 ) was chosen as top dose in the present experiment. In our study lead acetate in 80 mg/kg dose increased the liver and kidney weight and the MCV value; decreased the PFC number of the spleen and the speci®c footpad swelling.…”