In laboratory animals, an adequate way to assess effects of environmental exposures on the immune system is to study effects on antigen-specific immune responses, such as after sensitization to T-cell-dependent antigens. This probably also applies to testing effects in the human population. It has thus been suggested that antibody responses to vaccination might be useful in this context. Vaccination responses may be influenced by a variety of factors other than environmental ones. One factor is the vaccine itself; a second is the vaccination procedure used. In addition, the intrinsic capacity of the recipient to respond to a vaccine, which is determined by sex, genetic factors, and age, is important. Psychological stress, nutrition, and (infectious) diseases are also likely to have an impact. We reviewed the literature on vaccine response. With regard to exogenous factors, there is good evidence that smoking, diet, psychological stress, and certain infectious diseases affect vaccination titers, although it is difficult to determine to what extent. Genetic factors render certain individuals nonresponsive to vaccination. In general, in epidemiologic studies of adverse effects of exposure to agents in the environment in which vaccination titers are used, these additional factors need to be taken into consideration. Provided that these factors are corrected for, a study that shows an association of exposure to a given agent with diminished vaccination responses may indicate suboptimal function of the immune system and clinically relevant diminished immune response. It is quite unlikely that environmental exposures that affect responses to vaccination may in fact abrogate protection to the specific pathogen for which vaccination was performed. Only in those cases where individuals have a poor response to the vaccine may exogenous factors perhaps have a clinically significant influence on resistance to the specific pathogen. An exposure-associated inhibition of a vaccination response may, however, signify a decreased host resistance to pathogens against which no vaccination had been performed.

In laboratory animals, an adequate way to assess effects of environmental exposures on the immune system is to study effects on antigen-specific immune responses, such as after sensitization to T-cell-dependent antigens. This probably also applies to testing effects in the human population. It has thus been suggested that antibody responses to vaccination might be useful in this context. Vaccination responses may be influenced by a variety of factors other than environmental ones. One factor is the vaccine itself; a second is the vaccination procedure used. In addition, the intrinsic capacity of the recipient to respond to a vaccine, which is determined by sex, genetic factors, and age, is important. Psychological stress, nutrition, and (infectious) diseases are also likely to have an impact. We reviewed the literature on vaccine response. With regard to exogenous factors, there is good evidence that smoking, diet, psychological stress, and certain infectious diseases affect vaccination titers, although it is difficult to determine to what extent. Genetic factors render certain individuals nonresponsive to vaccination. In general, in epidemiologic studies of adverse effects of exposure to agents in the environment in which vaccination titers are used, these additional factors need to be taken into consideration. Provided that these factors are corrected for, a study that shows an association of exposure to a given agent with diminished vaccination responses may indicate suboptimal function of the immune system and clinically relevant diminished immune response. It is quite unlikely that environmental exposures that affect responses to vaccination may in fact abrogate protection to the specific pathogen for which vaccination was performed. Only in those cases where individuals have a poor response to the vaccine may exogenous factors perhaps have a clinically significant influence on resistance to the specific pathogen. An exposure-associated inhibition of a vaccination response may, however, signify a decreased host resistance to pathogens against which no vaccination had been performed.

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.

In this study, the prolonged low-dose exposure of mixtures of pesticides has been examined on hematological parameters and components of the immune defense in occupationally exposed humans. This investigation was carried out in five field studies in: the Netherlands (flower bulb growers, mainly re-entry workers), Italy (vineyard workers), Finland (potato farmers), and Bulgaria (workers from a zineb factory and greenhouse workers). Immunotoxicity was studied by measuring hematological parameters, complement, immunoglobulins, lymphocyte subpopulations, natural killer cells, autoimmunity, and antibody responses to hepatitis B vaccination. The total study population consisted of 248 pesticide-exposed and 231 non-occupationally exposed workers. As a surrogate measure of pesticide exposure the urinary excretion of ethylenethiourea (ETU), the main metabolite ethylenebisdithiocarbamates was measured. A significantly higher level of ETU in occupationally exposed subjects compared with controls (2.7 ± 8.1 μg/g vs 0.5 ± 3.7 μg/g creatinine) was found. Statistically significant differences, albeit very low, were found for complement C3 and C4 and the immunoglobulin classes IgG4 and IgA. For complement and IgG4, the levels were slightly increased and the level of IgA was decreased. In the lymphocyte populations, the CD8 subpopulation was increased. No effects were found on autoimmune antibodies and antibody response to hepatitis vaccination. In conclusion, pesticide exposure under various work place conditions in Europe was associated only with some subtle effects on the immune system, which may suggest that occupational exposure to pesticides does not influence the immunologic system in a clinically significant fashion, and does not pose a significant health risk to the exposed subjects.

The aim of this study was to investigate the health effects induced by exposure to the fungicide mancozeb in Italian vineyard workers. Ninety-three Italian subjects entered the study - 48 vine-growers intermittently exposed to mancozeb and 45 healthy controls. The subjects were investigated three times: before the seasonal application of pesticides (T0), 30 days after the beginning of the application period (T30), and 45 days after T0 (T45). At T0 the comparison between agricultural workers and controls showed a higher prevalence of cold or flu symptoms, a statistically significant lower percentage of monocytes, higher absolute count of T lymphocytes, CD4 and natural killer cells, and lower plasma levels of IgA and IgM in workers. Such differences were not confirmed at T30 and T45. In fact at T30 in exposed workers, besides a significant increase of urinary ethylenethiourea, confirming mancozeb exposure, T lymphocytes, CD4 and natural killer cells, IgA and IgM returned to values comparable to those observed in controls. Moreover, no other differences in clinical signs, haematological, and immune parameters, such as the immune functional capability evaluated as a response to hepatitis B vaccination, was observed. Altogether the differences between exposed and controls were not consistently correlated to any clinical impairment and suggest that the seasonal application of mancozeb does not pose a significant health risk to exposed subjects.