Effects of pesticide exposure on the human immune system.

Epidemiological evidence from Western countries indicates that the prevalence of diseases associated with alterations in the immune response, such as asthma, certain autoimmune diseases and cancer, are increasing to such an extent that it cannot be attributed to improved diagnostics alone. There is some concern that this trend could be, at least, partially attributable to new or modified patterns of exposures to chemicals, including pesticides. The purpose of this article is to review the evidence on pesticide immunotoxicity in humans. Overall, the available data are inadequate to draw firm conclusions on the immunotoxic risk associated with pesticide exposure. The available studies on the effects of pesticides on the human immune system have several limitations, including limited data on exposure levels, heterogeneity of the applied methods, and difficulties in assessing the prognostic significance of observed slight changes and in the interpretation of the reported findings. Further studies are needed and preferably as prospective studies, comparing pre- and post-exposure data in the same group of subjects and including an appropriate non-exposed control group. More knowledge is required regarding the prognostic significance of the small changes observed.

Immune effects and exposure to ethylenebisdithiocarbamate pesticides in re-entry workers in the Netherlands.

Ethylenebisdithiocarbamates are widely used as fungicides in agriculture. Although EBDC's have a low acute toxicity, they are suspected to have immune effects at low doses. However, little human studies on these effects have been published. In the Netherlands, a study was conducted among pesticide exposed workers aimed at evaluating the short-term and long-term immune effects of exposure and the relation between ethylenebisdithiocarbamate and immune effects. Forty-one re-entry workers and 40 nonexposed controls were medically examined; furthermore, immune parameters were determined in blood, and all participants filled in a questionnaire regarding exposure and outcome parameters. The level of ethylenethiourea in urine was determined as indicator of exposure. No relevant adverse immune effects were found in the pesticide exposed workers compared with the nonexposed controls. Also no exposure response relationship between immune effects and ethylenebisdithiocarbamate in urine was found. This finding might be due to very low exposure levels of the re-entry work but might also be due to a lack of immunotoxicity of ethylenebisdithiocarbamate at normal exposure levels.

Occupational exposure to ethylenebisdithiocarbamates in agriculture and allergy: results from the EUROPIT field study.

This epidemiological study was carried out to evaluate the possible association between occupational exposure to ethylenebisdithiocarbamates (EDBC) and allergy. The study was conducted in four countries in the European Union: The Netherlands, Finland, Italy and Bulgaria. A total of 248 workers exposed to EDBC and 231 non-occupationally exposed subjects entered the study. Exposure to EDBC was measured as urinary ethylenethiourea (ETU) in urinary samples collected at baseline and after 30 days of exposure. Several effect parameters were evaluated including questionnaire data on allergy, Phadiatop, a general allergy test, and specific IgE parameters. These data were also collected at baseline and after 30 days of exposure. Cross-sectional as well as longitudinal comparisons were made, adjusted for potential confounding factors. No association was found between exposure status, EDBC levels and allergic contact dermatitis, allergic rhinitis, food allergy or atopy as measured by the Phadiatop. The prevalence of skin irritation was elevated in the Dutch field study only and is more likely a result of plant contact rather than EDBC exposure. Occupational exposure to sunlight was noted to have a protective effect on atopy in terms of IgE positivity. We conclude that the EDBC exposure levels experienced in our field study are not associated with increased prevalence of allergic symptoms or allergy.

Asthmatic symptoms after exposure to ethylenebisdithiocarbamates and other pesticides in the Europit field studies.

We conducted a multicenter prospective study to assess the effects of occupational exposure to ethylenebisdithiocarbamate fungicides and/or other pesticides on self-reported asthma and asthmatic symptoms. This multicenter study was conducted among 248 workers exposed to pesticides and 231 non-exposed workers from five field studies. The five field studies were carried out in The Netherlands, Italy, Finland, and two studies in Bulgaria. Subjects constituting this cohort completed a self-administered questionnaire at baseline (before the start of exposure). Ethylenethiourea in urine was determined to assess exposure to ethylenebisdithiocarbamates. In multivariate analyses adjusted for all potential confounders (age, education, residence, smoking, gender, and field study), we found inverse associations, all not statistically significant, between occupational exposure to pesticides and asthma diagnosis (OR 0.41; 95% CI 0.15-1.11), complains of chest tightness (OR 0.60; 95% CI 0.36-1.02), wheeze (OR 0.56; 95% CI 0.32-0.98), asthma attack (OR 0.52; 95% CI 0.12-2.25), and asthma medication (OR 0.79; 95% CI 0.25-2.53). Furthermore, we reported null associations for multivariate analysis using ethylenethiourea as determinant for exposure. Although exposure to pesticides remains a potential health risk, our results do not suggest an association between exposure to ethylenebisdithiocarbamates and/or other pesticides used in our study on asthma and asthmatic symptoms.

[Current methodologic approaches to the study of various delayed effects of pesticides]. / Suvremenni metodologichni podkhodi pri izuchavane niakoi otdalecheni efekti na pestitsidite.

Studies on the possibilities of origination of remote sequelae (embryotoxic and teratogenic, gonadotropic, mutagenic, carcinogenic, alterations in cardiovascular system, etc) under the effect of the wide application of pesticides in the practice is one of the most important aspects of the present-day toxicology. Numerous of our studies in that field are directed to the pesticides, to fungicides in particular, the greater part of them being with mechanisms of biological activity, triggering changes in DNA synthesis and disturbances in cellular respiration. The results from our experimental studies are presented in the communication, with an aspect of alterations in the gonads, embryotoxicity and teratogenicity, of representatives of various groups of chemical preparations for plant protection. The eventual use of those data in the prognosis of potential risk for humans is discussed. Model conditions are proposed for a more thorough assessment and more accurate determination of threshold levels of effect with a view to their utilization in hygienic standardization.

Study on the long-term effects of some pesticides.

The hygienic significance of the studies on pesticides from the aspect of their "long-term" effects upon the individual and the generations are emphasized. The basic methods and approaches used in the Laboratory of long-term effects with chemical etiology at the IHOH, Sofia, are discussed, namely for detecting the changes in gonads, reproduction and generation, embryotoxic and teratogenic effects, and changes in cardiovascular system. The results are discussed, namely: fundasol--the effect on gonads, generations, embryotoxic and teratogenic effects, changes in the cardiovascular system; endodan--changes in gonads, reproduction, embryotoxicity; basfungin--embryotoxic and teratogenic effects. All of these studies were performed for the purpose of threshold levels, establishment hygienic standardisation and prognosis of the potential risk for human.

[Potential teratogenic action of the mycelium of the higher fungus, Polyporellus squamosus]. / Prouchvane ne vuzmozhnoto teratogenno deistvie na mitsel ot visshata guba Polyporellus squamosus.

The influence on the embryonic development of food with only source of protein derived from the mycelium of the higher fungus Polyporellus squamosus, was studied in a group of 90 pregnant rats. Animals fed caseine and standard food pressed into briquettes as source of protein served as controls. On the 17-th and 18-th gestation day 8 animals were examined and the number of of lutein bodies and fetuses was checked up. Anomalies were serched in the fetuses, by use of the method of Dawson and Wilson. The progeny of rats treated during gestation was examined on the 21-st day of life, by using a number of blood, integral and biochemical parameters (GOT, GPT, AP, SDH, catalase, sulfhydryl groups, soluble, protein). Proceeding from the results obtained, the authors rule out any teratogenic and embryotoxic activity of the mycelium of Polyporellus squamosus, under the aforegoing experimental conditions.

[Embryotoxic and teratogenic action of some pesticides]. / Embriotoksichno i teratogenno deistvie na niakoi pestitsidi

The authors carried out experiments on white rats in order to evaluate embriotoxic and teratogenic effect of pesticides: cyneb, mneb, cypromate, basfungine, remrod, dipterex and bromex. The preparations were administered oraly as followed: 1) singly in the course of whole pregnancy in a dose of 1/2 LD50 and lower doses till finding single nonacting dose and 21 in the course of the whole pregnancy in doses rangling from the determined single threshold dose till finding minimal acting dose during multiple application and nonacting teratogenic dose under the same conditions. The authors examined the changes in some liver enzymic systems of the mother and fetus. It was established that there was raised actitity of LDH, A1Ph, AcPh, glucose -6-phosphat-dehydrogenase and HEA with degree differences in both examined categories - the mother and fetus. Single treatment of pregnant rats during the period of organogenesis induced anomalies in the development of the nervous system; of the skeletal system - facial cranium, extremities, tail as well as functional and biochemical changes. The authors determined teratogenically nonacting doses for single application: for cyneb - 1000 mg/kg; for maneb - 50 mg/kg and for cypronat - 250 mg/kg.