EXTERNAL SCIENTIFIC REPORT APPROVED: 20/02/2017 Human biomonitoring data collection from occupational exposure to pesticides Risk & Policy Analysts Limited (RPA) IEH Consulting Limited (IEH) Health & Safety Laboratory (HSL) Main authors: Ruth Bevan (IEH), Terry Brown (IEH), Franziska Matthies (IEH), Craig Sams (HSL), Kate Jones (HSL), James Hanlon (RPA), Max La Vedrine (RPA) Abstract Human biomonitoring (HBM) as a tool for occupational exposure assessment has been reviewed, with a specific focus on pesticides. A systematic literature review (SLR) of available information on HBM of pesticides (or their metabolites) in occupational settings and from HBM studies/surveillance programmes has been carried out and the studies identified assessed for relevance and quality. HBM essentially involves the quantification of either a substance, one of its metabolites, or a surrogate marker of its effects in a biological sample obtained from a person who may have undergone an exposure. Thus, HBM is generally considered to be an estimate of exposure, rather than a measure of health. Over the past 10 to 20 years there has been an expansion in the use of HBM, especially into the field of environmental and consumer exposure analysis, and it is currently well-developed and widely used in both the occupational and environmental settings worldwide. As with any tool, HBM has its strengths and weaknesses and appreciation of these promotes the development of approaches to minimise their effects. Although HBM has been extensively used for monitoring worker exposure to a variety of pesticides, epidemiological studies of occupational pesticide use were seen to be limited by inadequate or retrospective exposure information. Very limited data was identified examining seasonal exposures and the impact of PPE, and many of the studies used HBM to assess only one or two specific compounds. A wide variety of exposure models are currently employed for health risk assessments and biomarkers are often used to evaluate exposure estimates predicted by a model. From the 178 publications identified to be of relevance, 41 individual studies included herbicides, 79 individual studies included insecticides, and 20 individual studies included fungicides. Remaining studies related to mixtures or non-specific biomarkers for groups of pesticides. Although a number of current limitations were identified, there is evidence within the literature for a potential role of HBM in occupational health and safety strategies, as both a tool for refined exposure assessment in epidemiology studies and to contribute to the evaluation of potential health risks from occupational exposure to pesticides. Some key issues were considered that would need to be overcome to enable implementation of HBM as part of the occupational health surveillance for pesticides in Europe. These included issues around priorities for the development of new specific and sensitive biomarkers, the derivation and adoption of health-based guidance values, development of QA schemes to validate inter-laboratory measurements, good practice in field work and questionnaire design, consideration of the extended use of biobanking and the use of HBM for post-approval monitoring of pesticide safety. © European Food Safety Authority, 2017 Key words: exposure assessment; human biomonitoring; occupational exposure; pesticides. Question number: EFSA-Q-2015-00770 Correspondence: [email protected] www.efsa.europa.eu/publications EFSA Supporting publication 2017:EN-1185 Human biomonitoring for occupational exposure to pesticides Disclaimer: The present document has been produced and adopted by the bodies identified above as authors. This task has been carried out exclusively by the authors in the context of a contract between the European Food Safety Authority and the authors, awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Acknowledgements: We acknowledge the generous time given by, Dana Barr, Silvia Fustinoni, Paul Hamey and Len Levy, in reviewing a draft of this document and providing valuable comments. Suggested citation: RPA, HSL, IEH 2017. Human biomonitoring data collection from occupational exposure to pesticides – Final Report, EFSA supporting publication 2017:EN-1185. 207 pp. © European Food Safety Authority, 2017 Reproduction is authorised provided the source is acknowledged. www.efsa.europa.eu/publications 2 EFSA Supporting publication 2017:EN-1185 Human biomonitoring for occupational exposure to pesticides Summary A systematic review of the literature databases Scopus, Web of Science and PubMed for the period 1990 to 2015 (December) was carried out to to provide an overview on the use of HBM as a tool for occupational exposure assessment refinement, identifying advantages, disadvantages and needs for further development (first objective). The search identified 2096 publications relating to the use of HBM to assess occupational exposure to pesticides (or metabolites). Additional information was collated from individual searches to identify grey literature and reports, international evaluations or monographs and conference proceedings of appropriate societies/organisations and any associated journals. HBM essentially involves the quantification of either a substance, one of its metabolites, or a surrogate marker of its effects in a biological sample obtained from a person who may have undergone an exposure. Thus, HBM is generally considered to be an estimate of exposure, rather than a measure of health. Over the past 10 to 20 years there has been an expansion in the use of HBM, especially into the field of environmental and consumer exposure analysis. As with any tool, HBM has its strengths and weaknesses and appreciation of these promotes the development of approaches to minimise their effects. Several aspects have been highlighted for further development to improve the use of HBM for pesticide exposure assessment. These include: strategies to improve or standardise analytical quality; improving the availability of reference material for metabolites; integration of HBM data into mathematical modelling; exposure reconstruction; improvements in analytical instrumentation; and increased availability of human toxicology data. A review of available HBM studies/surveillance programmes conducted in EU/US occupational settings was carried out to identify pesticides (or metabolites) both persistent and not persistent, for which biomarkers of exposure (and possibly effect) are available and validated (second objective). A two- tiered screening process that included quality scoring for HBM, epidemiological and toxicological aspects, was utilised to identify those studies of most relevance, resulting in 178 studies being identified for critical review. In parallel with the screening of identified studies, a Master Spreadsheet was designed to collate data from these papers, which contained information relating to: study type; study participants; chemicals under investigation; biomarker quality check; analytical methodology; exposure assessment; health outcome/toxicological endpoint; period of follow-up; narrative of results; risk of bias and other comments. HBM has been extensively used for monitoring worker exposure to a variety of pesticides. Epidemiological studies of occupational pesticide use were seen to be limited by inadequate or retrospective exposure information, typically obtained through self-reported questionnaires, which can potentially lead to exposure misclassification. Some examples of the use of job exposure or crop exposure matrices were reported however little validation of these against actual exposure data had been carried out. Very limited data was identified that examined seasonal exposures and the impact of PPE, and many of the studies used HBM to only assess one or two specific compounds. A wide variety of exposure models are currently employed for health risk assessments and biomarkers have also often been used to evaluate exposure estimates predicted by a model. From the 178 publications identified to be of relevance, 41 individual studies included herbicides, and of these, 34 separate herbicides were identified, 15 of which currently have approved status for use in the EU. Similarly, of the 90 individual studies that included insecticides, 79 separate insecticides were identified, of which 18 currently have approved status for use in the EU. Twenty individual studies included fungicides, with 34 separate fungicides being identified and of these 22 currently have approved status for use in the EU. The most studied herbicides (in order) were shown to be: 2,4-D > atrazine > metolochlor = MCPA > alachlor = glyphosate. Similarly, the most studied insecticides (in order) were: chlorpyrifos > permethrin > cypermethrin = deltamethrin > malathion, and the most studied fungicides were: captan > mancozeb > folpet. A critical review of the collected information is provided, aiming at clarifying the contribution of HBM to the evaluation of potential health risks from pesticides exposure in occupational settings, and www.efsa.europa.eu/publications 3 EFSA Supporting publication 2017:EN-1185 The present document has been produced and adopted