Ann. occup. Hyg., Vol. 46, No. 5, pp. 465-477, 2002
© 2002 British Occupational Hygiene Society
Published by Oxford University Press
A Job–Exposure Matrix for Potential Endocrine-disrupting Chemicals Developed for a Study into the Association between Maternal Occupational Exposure and Hypospadias
1 Institute of Occupational Health, University of Birmingham, Birmingham B15 2TT; 2 Centre for Environmental Technology, Imperial College of Science, Technology and Medicine, TH Huxley School of Environment, Royal School of Mines, London; 3 Environmental Epidemiology Unit, London School of Hygiene and Tropical Medicine, London; 4 Faculty of Life and Health Sciences, University of Ulster; 5 Office for National Statistics, UK
Received 7 September 2001; in final form 17 January 2002
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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A study to assess the association between the prevalence of hypospadias and maternal occupational exposure to potential endocrine-disrupting chemicals was carried out using data from the congenital anomaly register of the Office for National Statistics. The occupation of the mother is recorded in this register and to facilitate the assessment of maternal occupational exposure, a specific job–exposure matrix for potential endocrine-disrupting chemicals was developed. Seven categories of contaminants were evaluated (pesticides, polychlorinated organic compounds, phthalates, alkylphenolic compounds, bi-phenolic compounds, heavy metals and other substances). Maternal occupations were all coded using the 1980 version of Categories of Occupations. Three occupational hygienists assessed the likelihood of exposure (unlikely, possible, probable) to these seven substance groups for all 348 possible job titles independently. Almost 30% of the job titles were classified as exposed to at least one substance category (possible or probable), with
16% of the job titles being probably exposed to at least one substance category. Some examples of occupations with probable exposure to potential endocrine-disrupting chemicals include: farm workers, electricians, workers in the plastics industry, painters, printers, hairdressers, dental practitioners, laboratory workers, textile workers and cleaners. It is recognized that there are a lot of limitations to the use of job–exposure matrices in general and with the matrix presented in this paper in particular. However, the matrix forms the basis on which further developments on occupational exposure assessment of potential endocrine-disrupting chemicals could be founded. In addition, the job–exposure matrix has identified areas where more exposure information is required. For example, exposure to potential endocrine-disrupting chemicals can occur in occupations such as hairdressing and workers in beauty salons, where the working population is more likely to be female and for which little data exist on levels of exposure.
Keywords: job–exposure matrix; endocrine disrupters; maternal exposure; hypospadias
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Hypospadias is a congenital malformation of the penis in which the urethral opening is abnormal in position; in severe cases it is on the shaft of the penis. It has an estimated prevalence at birth of between 1 and 2 per 1000 (i.e. between 2 and 4 per 1000 males) in Europe (Calzolari et al., 1986; Stoll et al., 1990; EUROCAT Working Group, 1997). There appear to be large differences in incidence of hypospadias between countries and increasing trends have been reported in European countries and the USA (Matlay and Beral, 1985; Toppari et al., 1996; Paulozzi et al., 1997; Dolk, 1998), although this could be due to differences in reporting of hypospadias and case ascertainment in the surveillance schemes. In European countries this trend appears to have levelled off during the 1980s (Toppari et al., 2001).
It has been postulated that hypospadias could be linked to maternal exposure to endocrine-disrupting chemicals (Toppari et al., 1996; Burdorf and Nieuwenhuijsen, 1999; Joffe, 2001). Endocrine-disrupting chemicals are exogenous substances that cause adverse health effects through interference with the endocrine system, either by mimicking hormones (agonists), binding to receptor sites without activation and thereby antagonizing endogenous hormones, interfering with the synthesis or degradation of hormones or in some other way (in)directly interfering with the functioning of hormones. Examples of potential endocrine-disrupting chemicals include dioxins, polychlorinated biphenyls (PCBs), organochlorine and organophosphorus pesticides and phytoestrogens such as those in soy products (Toppari et al., 1996).
To assess whether there is an association between the prevalence of hypospadias and maternal occupation and exposure to endocrine-disrupting chemicals, a study was initiated using data from the congenital anomaly register of the Office for National Statistics. The occupation of the mother is recorded in this register and a specific job–exposure matrix was developed to assess occupational exposure to potential endocrine-disrupting chemicals.
This paper presents the methods used to develop this matrix and the resulting assessment of exposure. Results of the study into the association between maternal exposure to potential endocrine-disrupting chemicals and hypospadias are presented elsewhere (Vrijheid et al., 2000).
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Following a literature review (e.g. Colborne et al., 1996; Toppari et al., 1996; Environment Agency, 1998) and examination of some relevant web sites such as ‘Introduction to hormone disrupting chemicals’ (http://website.lineone.net/~mwarhurst/index.html), a list of substances with endocrine-disrupting potency was formed. As the information on occupation of the mother was only provided in general categories, it was not possible to develop a very substance-specific matrix. Therefore, it was necessary to determine a number of distinct substance categories (Table 1). These substance categories were: (1) pesticides, (2) polychlorinated organic compounds, (3) phthalates, (4) alkylphenolic compounds, (5) bi-phenolic compounds, (6) heavy metals and (7) a catch-all for other substances (parabens, butylated hydroxyanisole, phytoestrogens and synthetic steroids). There is no expectation that the list of potential endocrine-disrupting chemicals given in Table 1 is exhaustive, nor does inclusion in this table mean that it is beyond all doubt that the substances all have endocrine-modulating potencies. However, the seven substance categories represent the majority of the main potential endocrine-disrupting chemicals.
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Maternal occupations were all coded into 348 job titles from the 1980 version of Categories of Occupations (OC80). Subsequently, three occupational hygienists with wide research experience in occupational exposure assessment (M.v.T., M.J.N. and K.G.) assessed the likelihood of exposure to these seven substance groups for all 348 possible job titles independently. Information on the substances, summarized in Table 1, was provided to all assessors to assist in the assessment of exposure. The assessments were carried out by coding all job titles for the seven substance categories according to the following three definitions:
1. it is very unlikely that exposure occurred amongst workers with this job title;
2. there is a possibility that some of the workers with this job title had exposure (but the probability is fairly low);
3. the probability exists that at least a proportion of the workers with this job title had some exposure.
No distinction was made in the assessment of exposure between the various routes of exposure (airborne, dermal or ingestion).
statistics were calculated to investigate the inter-rater agreement. Subsequently, consensus was reached by discussion between the coders if there was a disagreement of two categories in the coding (i.e. one coder with assessment 0 and one with assessment 2). Otherwise, the exposure category with which the majority of the experts agreed (at least two out of three) was chosen as the exposure assessment in the job–exposure matrix.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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After completion of the independent assessment of exposure, results were compared between the coders. Table 2 provides the percentage of jobs that were classified as either exposure code 1 (possible) or 2 (probable) in each substance category by each expert coder and the median or consensus assessments. Disagreement across two categories, requiring consensus by discussion, occurred in 137 assessments (out of 7 x 348 = 2436), most often for phthalates (n = 35 job titles) and alkylphenolic compounds (n = 38 job titles). For pesticides there were only six job titles with this extent of disagreement. The final job–exposure matrix is shown in the Appendix.
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Exposure prevalence amongst the job titles was highest for the alkylphenolic compounds, with 15.5% of job titles being coded as at least possible exposed and 7.5% as probable exposed. For phthalates 12.9% of the job titles were coded as at least possible exposed, with 5.7% probable exposed. For the other substance categories the percentage of job titles coded as at least possible exposed was <10% and the percentage of job titles coded as probable exposed was <5%. Of the 348 job titles, 102 (29.3%) were coded as having at least one possible or probable exposure, whilst 57 (16.4%) had at least one probable exposure to one of the substance categories.
It is evident from Table 2 that there were some substantial differences between the expert coders in their original and independent assessments. Expert 2 was generally more likely to code a job as at least ‘possible’ exposed compared with the other two experts, although expert 1 most often coded for a ‘probable’ exposure. Table 3 provides the results of the inter-rater agreement between the three expert coders for the various substance categories. From this it can be seen that only for pesticides, when comparing exposure category 2 (probable) versus exposure category 0 (unlikely) or 1 (possible), was a reasonably high statistic found (0.77). For all the other substance categories the agreement between the three expert coders was moderate to poor. The agreement between experts 1 and 2 was in general somewhat better than the agreement between experts 1 and 3 and 2 and 3 (data not presented).
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For each substance category Table 4 provides some examples of occupations where exposure is expected. Farm workers are exposed to pesticides and alkylphenolic compounds (as a carrier of the pesticides). Electricians are exposed to polychlorinated organic compounds, due to working with old electrical installations, and phthalates from fumes when soldering. Workers in the plastics industry are exposed to phthalates and bi-phenolic compounds, whilst painters are exposed to phthalates and alkylphenolic compounds and printers to phthalates. Hairdressers are exposed to phthalates as these are used in various cosmetic products such as hair sprays, whilst dental practitioners are exposed to alkylphenolic compounds and heavy metals (mercury). Laboratory workers, textile workers and cleaners are exposed to alkylphenolic compounds due to the use of detergents, whilst people in the armed forces, petrol pump attendants, traffic wardens, gold and silversmiths, glass, ceramic and pottery workers and welders are exposed to heavy metals. No occupations were identified with probable exposure to the category ‘other endocrine-disrupting substances’.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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A job–exposure matrix was developed for assessing the likelihood of occupational exposure to potential endocrine-disrupting chemicals. Initial coding showed discrepancies between coders, particularly for phthalates and alkylphenolic compounds, and therefore consensus was reached when two coders had maximum disagreement. The job–exposure matrix was used in a study investigating the risk of hypospadias in relation to maternal occupational exposure to potential endocrine-disrupting chemicals, using data from the congenital anomaly register of the Office for National Statistics (Vrijheid et al., 2000).
It is recognized that there are several limitations in the use of job–exposure matrices, especially when the matrices were developed for other studies and other populations (Kromhout et al., 1992; Tielemans et al., 1999). A study in the USA into occupational exposures in relation to birth defects also showed that there were considerable discrepancies between the assessment using an external job–exposure matrix and expert assessments (Louik et al., 2000). Due to the specific requirements of the assessment of potential endocrine-disrupting chemicals, such as the assessment of exposure irrespective of the route of exposure and the assessment of low levels of exposure, it was necessary to develop a new job–exposure matrix. However, due to the lack of detailed information on working conditions and practices it was not possible to assess the level of exposure to any of the seven substance categories and, therefore, it was decided to assess the likelihood of exposure as unlikely, possible or probable. This assessment did not reflect intensity, duration or frequency of exposure.
Almost 30% of the job titles were considered to be exposed to at least one substance category (possible or probable), with 16% of the job titles considered to be probably exposed to at least one substance category. These numbers should not be confused with a prevalence of exposure, as the numbers of subjects with these occupations are not taken into account. An occupation was recorded for 35 952 cases of congenital anomalies recorded in the periods 1980–89 and 1992–96 in the National Congenital Anomaly System (Vrijheid et al., 2000). Of these subjects, 13.6% had at least one possible or probable exposure according to the job–exposure matrix, with the highest exposure prevalence for alkylphenolic compounds (10.4%) and phthalates (9.3%). Examples of occupations that were responsible for these exposures in this population were cleaners, laboratory workers and farm workers (alkylphenolic compounds) and hairdressers and painters (phthalates).
The agreement between the expert coders in the exposure assessment was moderate to poor for most categories; only for pesticides was there good agreement between the experts. The reason for the poor assessment was the lack of information on occupations and tasks. The assessment was based upon very broad occupational titles, such as ‘chemical, gas and petroleum process plant operators’ or ‘production fitters (electrical, electronic)’. Ideally, information should be gathered from questionnaires, job-specific information and measurements to improve the exposure assessment (Tielemans et al., 1999).
Exposure assessments to potential endocrine-disrupting chemicals are prone to numerous complications. The time window for an effect of endocrine-disrupting chemicals to occur in the offspring may be very short, possibly not longer than a few weeks during early pregnancy, whilst subjects could be exposed to a mixture of several endocrine-disrupting chemicals (Burdorf and Nieuwenhuijsen, 1999). Little is known about the possible interactions that occur between different endocrine-disrupting chemicals when the individual is exposed simultaneously.
A large number of substances have been identified in recent years with at least some endocrine-modulating potency, and these data have been reflected in this job–exposure matrix. However, the endocrine-disrupting potency of the substances and mechanisms by which these substances exert their effect can vary widely (Joffe, 2001) and the exposure categories given in this paper are not uniform with respect to endocrine-disrupting potency.
However, despite these flaws in the assessment produced here, the job–exposure matrix can be of value as an initial assessment of exposure and can form the basis for further improved exposure assessment, for example using job-specific questionnaires. In addition to improving the assessment of occupational exposure using more information on occupations and tasks, in particular with regard to the narrow time window, future research should also include assessments of potency of the various endocrine-disrupting chemicals and investigate the effects of simultaneous exposures to these chemicals.
The job–exposure matrix presented in this paper allowed the huge amount of routinely collected health data or surveillance data to be analysed as fully as possible with respect to the endocrine-disrupting hypothesis. The matrix could form a platform on which further developments on occupational exposure assessment of potential endocrine-disrupting chemicals can be based. In addition, the job–exposure matrix has identified areas where more information is required on exposure. For example, exposure to potential endocrine-disrupting chemicals can occur in occupations such as hairdressers and workers in beauty salons, where the working population is more likely to be female and for which little data exist on levels of exposure.
Acknowledgements—This work was funded by the Department of Health, the Health and Safety Executive and the Department for Environment, Food and Rural Affairs. The views expressed in this paper are those of the authors and not necessarily those of the above sponsors.
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FOOTNOTES |
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* Author to whom correspondence should be addressed. E-mail: m.j.a.van_tongeren@bham.ac.uk
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