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Toxicological evaluation of the immune function of pesticide workers

Deliverables

A study of the immunotoxicity of ethylene bis dithocarbamate pesticides in vineyard workers was performed in Italy. Exposure parameters and immune parameters were measured, and questionnaires were applied to the workers. The study revealed did not confirm the slight immunostimulatory effects associated with mancozeb exposure observed in previous studies, perhaps because the parameters measured (serum and cellular) are different from those taken into account in these previous studies.
A study of the immunotoxicity of zineb was performed in a zineb production factory in Bulgaria. Exposure parameters and immune parameters were measured, and questionnaires were applied to the workers. No major differences in immune status associated with exposure were detected
In the two Bulgarian, the Finnish, the Italian, and the Dutch Field Studies, polymorphisms, and their frequencies of selected genes were assessed, and their interactions with exposure-effect parameters were evaluated. Glutathion-S-transferase and Cyp3A4, IL-1Ñ, IL-1Ò, and IL-1RA genotypes were similarly distributed among pesticide exposed and control population. Correlation analyses of the distribution of GSTM-1 and Cyp3A4 with ethylene thiourea, as an indicator of the level of exposure have not shown any significant effects. When taken into account the effect of polymorphism of IL-1 group of genes, only IL-1Ò genotype showed some effects. Overall analyses showed that people with homozygous polymorphism of this gene and exposed to pesticides showed lower level of anti-hepatitis B titters than those of wild type. However, by selecting a group of responders to vaccination, analyses showed that polymorphism of IL-1Ò predisposes to significantly higher levels of anti-Hb titers but exposure to pesticides does not affect this observation in any significant way. Hence, the study supported earlier findings of influence of IL-1Ò polymorphism on anti-Hb titters after immunization but declined any effect of pesticide exposure. Any immunological changes attributable to pesticide exposure do not contain significant confounding factor of genetic background as based on the analyses of the polymorphisms of selected genes.
An integral evaluation of all information gathering in the 5 field studies will provide information on pesticide exposure associated immune alteration in Europe. This evaluation is still in progress. Based on the experience gained, it will be possible to prepare protocols adequate to carry out "in field" studies addressed at agricultural workers. This will enable the conduction of studies, addressed at several health issues, and will encourage the collection of data in a field in which the available knowledge is small and several uncertainties still remain. This is a priority from the enlarging European Union, where most of the new EU-Countries and all the candidates are characterized by the presence of a workforce in which agricultural workers represent the mot important portion. After the end of the project, the whole EUROPIT Consortium has decided to continue cooperation in the frame of a multidisciplinary working group, with the objective of continuing the activities done and participating in further applications addressed at the collection of knowledge on the health status of agricultural workers, their occupational diseases and the related determinants of disease.
An epidemiological study of the immunotoxicity of mixture of pesticides in greenhouse workers in Bulgaria was performed. Exposure parameters and immune parameters were measured, and questionnaires were applied to the workers. No major differences in immune status associated with exposure to pesticides were detected.
An epidemiological study of the immunotoxicity of EBDTC and mixed pesticide exposure in agricultural (potato) workers was performed in Finland. Exposure parameters and immune parameters were measured, and questionnaires were applied to the workers. A deterministic model based on the information of questionnaires was developed for the exposure assessment of workers during the exposure period. The model is used with biomonitoring data in order to divide workers into homogenous exposure groups. The model also gives an estimate of exposure level if the biomonitoring result of the worker is not available. Also the EUROPOEM and German models were tested with the exposure data. The results of the study indicate significant suppression of T lymphocytes and inflammatory parameters in exposed workers compared to controls.
A questionnaire has been developed to collect information on the immune status of individuals exposed to pesticides, on confounding factors. The questionnaire has been validated, and translated into Finnish, Bulgarian, and Italian. It can be applied is epidemiological studies of immune alterations associated with pesticide exposure. It can be adapted for studies into immunotoxic effects of other agents. Protocols for laboratory analysis have been designed and are available.
Risk assessment is a key activity in health promotion at the workplace: based on risk assessment it is possible to define priorities, to highlight unacceptable health risks and to decide when workers need health surveillance. In occupational exposures to chemicals, the key action of risk assessment is the definition of the dose absorbed by the workers. In agriculture this is done only in few cases, due to the sector specificities, which make difficult to define "typical" scenarios and to perform measures that are representative and reproducible. In the frame of EUROPIT project, data have been collected on the "real" way of working of the workers under study. This brings about the possibility of defining "exposure profiles" for the activities taken into account and to highlight the main variables able to affect exposure levels, with the support of biological monitoring data. This will enable risk assessment in the situation under study, as well as comparison among different countries and areas. Exposure profiles are a very promising tool addressed at risk assessment in agriculture. The activities addressed at the definition of such as profiles are being carried out at the local level, for example in the Region of Lombardy, when a significant part of the EUROPIT Italian study have been carried out. The urinary ETU levels determined in control-unexposed subjects may be useful to estimate the reference value for the general population at a European level. The reference value is a useful tool for the interpretation of the biological monitoring data: in the absence of a biological limit value the reference value represents a necessary term of comparison to assess the presence or absence of occupational exposure.
A study of the immunotoxicity of dithiocarbamate pesticides in flower bulb growers was performed in the Netherlands. Exposure parameters and immune parameters were measured, and questionnaires were applied to the workers. In the study slight immunosuppressive effects were observed.

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