Occupational sensitization to epoxy resins in Northeastern Italy (1996–2010) Andrea Prodi1, Francesca Rui1, Anna Belloni Fortina2, Maria Teresa Corradin3, Francesca Larese Filon1 1
Clinical Unit of Occupational Medicine, University of Trieste, Italy, 2Dermatology Unit, Department of Pediatrics, University of Padua, Italy, 3Dermatology Unit, S. Maria degli Angeli Hospital, Pordenone, Italy Background: One of the main health concerns of epoxy resins is their role as skin sensitizer. This sensitization is not uncommon, because the prevalence ranges around 1–12% of the general population. Objectives: Perform a cross sectional study in a patch test population from Northeastern Italy to investigate the prevalence of epoxy resins sensitization among patients with suspected contact dermatitis. Subsequently, relate findings to patients’ occupation and evaluate time trend of prevalence. Methods: The final study database included 19 088 consecutive patients, tested from 1996 to 2010 in Northeastern Italy. Results: The overall prevalence of epoxy resins sensitization was 0.89%. Dermatitis most frequently involved hands (40.25%). In both sexes, we find a significant correlation in mechanics, woodworkers, and chemical industry workers; and in males only, among farmers and fishers, construction workers, and unemployed. We found significant increase of sensitization in construction workers in the analyzed period. Conclusions: The overall prevalence of sensitization to epoxy resins in Northeastern Italy is in line with other European countries, but we found an increased risk of sensitization in some professions and an increasing trend of prevalence in construction workers. Better preventive actions are strongly advised in higher risk professions, with particular attentions towards building sector.
Keywords: Epoxy resins, Patch test, Allergic contact dermatitis, Epidemiology
Introduction Occupational contact dermatitis to epoxy resins is an important health concern due to the wide diffusion of products containing this powerful hapten. Sensitization is often acquired after a short exposure time1 when workers are exposed to unhardened epoxy resin. Dermatitis predominantly occurs on the hands but can also involve the face. The primary route of exposure is airborn.2 Clinical manifestations can involve exposed and unexposed skin with important skin reactions that can cause sick leave, ill health retirement, or job changing in affected workers. Epoxy resins are a class of ubiquitous chemicals, polymers, and reactive prepolymers, which contain epoxide groups, widely used for their exceptional properties of hardness and impact resistance to heat, water, and chemicals, as well as their abilities to function as electric insulators and adhesives.3 A wide array of applications use epoxy-based materials including adhesives, composite materials (carbon Correspondence to: Andrea Prodi, Unita` Clinica Operativa di Medicina del Lavoro, Dipartimento di Scienze Medico Chirurgiche e della Salute, Universita` degli Studi di Trieste, Centro Tumori – Via della Pieta`, 19 Trieste I-34129, Italy. Email: [email protected]
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fiber, fiberglass reinforcements), paintings and coatings, industrial tooling and composites, electrical systems and electronics, consumers and marine applications, the aerospace industry, and biology. Seventy-five to ninety percent of epoxy resins are based on epichlorohydrin and bisphenol A, which react to form diglycidylether of bisphenol A (DGEBA). The diglycidyl ether of bisphenol F (DGEBF) is the base of approximately 1% of epoxy resins.4 Epoxy resins systems (epoxy monomer, hardener, reactive diluent, and/or other additives) may pose health hazards in the occupational environment during the production or use of resins.5 Diglycidylether of bisphenol A is a sensitizer for approximately 60–80% of patients with allergic contact dermatitis to epoxy resins.6 Sensitization may occur in unhardened epoxy resin handlers, while fully cured epoxy resin is non-irritating and nonsensitizing4 (although some traces of epoxy monomers may still be present due to an incomplete curing). This study investigated the prevalence of epoxy resins sensitization in a population from Northeastern Italy, evaluated between 1996 and 2010, (1) in order to
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analyze for temporal trend of this sensitization, (2) to find out whether it was stable over time in the overall population, (3) as well as by occupational category, and (4) to investigate for associations between epoxy resins sensitization and occupations in a geographical context.
Methods Study subjects From 1996 to 2010, 19 666 consecutive patients with symptoms and/or signs of suspected allergic dermatitis were patch tested in eight departments of dermatology or occupational medicine in Northeastern Italy (Belluno, Bolzano, Padua, Pordenone, Rovereto, Rovigo, Trento, and Trieste). Individual characteristics, occupational history, and personal and family history of atopy (asthma and/or allergic rhino-conjunctivitis with at least one positive prick test reaction to relevant aeroallergens) were collected through a standardized questionnaire.7 After excluding 578 patients for missing data (related to personal history – e.g. sex or age – or incomplete patch testing), 19 088 consecutive subjects were included in the analysis. All subjects were affected by dermatitis, most of them with moderate/severe reactions. All subjects were categorized by occupation, collapsing related job groups into larger ones (e.g. nurses, physicians, and other hospital workers were collapsed into the ‘‘health care workers’’ category). Similarly, body site categories were collapsed (e.g. fingers, palm, and dorsum hands were collapsed into ‘‘hands’’). We performed occupational category related analysis on 16 267 subjects, discarding 3399 because of the incomplete or inaccurate collection of subject’s occupational anamnesis. Exposure was estimated based on the subject’s current profession. Because sensitization is often acquired after a short exposure,1 we did not take into account historical occupational anamnesis but instead, only the subject’s job at the time of evaluation Subjects was classified by profession, and statistical analyses were stratified by sex and age differences to minimize confounding (described below). All patients provided written informed consent.
Patch tests Finn ChambersH on ScanporH (Epitest Ltd, Tuusula, Finland) and allergens from FIRMA (Firenze, Italy) were used to patch test patients with the European baseline series.8 The tested allergens included epoxy resins (Araldite 1% in pet). Patches were applied on the upper back and removed after 48 hours. The sites were examined on removal and 24 or 48 hours after removal, according to International Contact Dermatitis Research Group guidelines.9 Reactions of grades z, zz, and zzz in the second examination were considered to be
Occupational sensitization to epoxy resins in northeastern Italy
positive. Dubious or nebulous reactions (¡, ‘‘?’’) were considered negative.
Statistical analysis Data analysis was performed using STATA v. 12.0 software (Stata Corp., LP, College Station, TX, USA). Categorical data were cross-tabulated into k6k contingency tables. The associations between patch test results, patient age (quintiles: #25, 26–34, 35–44, 45–57, and §58 years), year of patch testing (according to 3-year calendar periods: 1996–1998, 1999–2001, 2002–2004, 2005–2007, 2008–2010), and occupation were investigated using multivariate logistic regression analysis. Odds ratios and 95% confidence intervals were estimated from the coefficients and the standard errors of logistic regression output. Logistic analysis was conducted separately by gender, adjusting results by age, with white-collar workers as the reference group (we can assume that epoxy resins sensitization in this professional group is likely non-occupationally related). Trend tests across ordered groups were performed using Cuzick’s test for trend. Patients with missing data were excluded from the analysis. A P-value of ,0.05 was used to denote statistical significance.
Results The study population included 12 820 women (67.2%) and 6268 men (32.8%). The overall prevalence of epoxy resin sensitization was 0.89% (0.64% of women and 1.39% of men). Table 1 shows the distribution of professions within the study population by sex. In this table, we considered 16 267 patients [10 989 females (67.6%) and 5278 males (32.4%)], excluding the remaining patients because of incomplete or inaccurate determination of job category. For both sexes, the prevalence of epoxy resins sensitization remained relatively stable during the study, without showing any statistically significant variation (Fig. 1) (P-value for trend: females P50.435, males P50.461). The prevalence was rather homogeneous among the considered age quintiles (P-values for trend: females P50.924, males P50.122), with the only exception in males over 58 years old (fifth quintile). The prevalence in this age group was less than half of the average prevalence in males (0.53%), a statistically significant difference (P50.013) (Fig. 2). Dermatitis most frequently involved hands (40.25% for all patients and 51.97% for patients sensitized to epoxy resins). In Table 2, we compared subjects’ positive for epoxy resins sensitization to subjects negative for epoxy resins (by sex). Among males, hands were more frequently sensitized to epoxy resins (57.58%) compared to subjects without sensitization for this body area; the statistically significant
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Occupational sensitization to epoxy resins in northeastern Italy
Figure 1 Prevalence of sensitization to epoxy resins, by sex, from 1996 to 2010.
difference being (OR 1.82, 95% CI 1.1–3.0). No other body site showed a statistically significant association. Table 3 reports the results of multinomial logistic regression analysis, adjusted by age, investigating for an association between sensitization to epoxy resins and occupation. For both sexes, we found a significant association to sensitization for mechanics (males: OR 2.48, 95% CI 1.03–6; females: OR 4.13, 95% CI 1.6–10.6), woodworkers (males: OR 3.87, 95% CI 1.2–12.5; females: OR 4.41, 95% CI 1.3–15.3), and chemical industry workers (males: OR 4.64, 95%
CI 1.3–17.2; females: OR 5.18, 95% CI 1.2–23). In males, we found a significant association for farmers and fishers (OR 3.88, 95% CI 1.04–14.4), construction workers (OR 5.2, 95% CI 2.4–11.2), and the unemployed (OR 4.44, 95% CI 1.2–16.5). For construction workers, we found a significant increase in sensitization over time from 1.4% (in 1996–1998 period) to 14.8% (in 2008–2010) (P50.004). Painters (20 males, 13 females) also had a high prevalence of sensitization to epoxy resins. We identified four subjects (12.1%) sensitized to resins, three males and
Table 1 Occupational categories of the study population Gender Job White-collar workers1 Household workers Retired Healthcare workers Construction workers Mechanics Maids and restaurant workers Other artisans Other occupations Unemployed Woodworkers Barbers, hairdressers Professional drivers Domestic workers Farmers and fishers Chemical industry workers Paper production workers Mechanical machines workers Upholsterers Total
Females 3003 2411 1327 1708 327 277 499 335 164 205 130 191 31 181 78 74 19 20 9
%
Males
%
Total
%
27.33 21.94 12.08 15.54 2.98 2.52 4.54 3.05 1.49 1.87 1.18 1.74 0.28 1.65 0.71 0.67 0.17 0.18 0.08
1369 28 1015 486 573 559 255 150 140 95 145 18 175 23 109 91 27 19 1
25.94 0.53 19.23 9.21 10.86 10.59 4.83 2.84 2.65 1.80 2.75 0.34 3.32 0.44 2.07 1.72 0.51 0.36 0.02
4372 2439 2342 2194 900 836 754 485 304 300 275 209 206 204 187 165 46 39 10
26.88 14.99 14.40 13.49 5.53 5.14 4.64 2.98 1.87 1.84 1.69 1.28 1.27 1.25 1.15 1.01 0.28 0.24 0.06
10 989
5278
16 267
1
White-collar workers: this group is primarily composed of clerks, but professors and students also are included.
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Figure 2 Prevalence of sensitization to epoxy resins, by sex, within considered age quintiles.
one female. However, given the small subsample, we included painters within the ‘‘construction worker’’ category.
exception in males older than 57 years (0.53%). This may be explained by the limited use of epoxy resins in the past, contributing to a lower exposure dose or reflect a decrease in sensitization because of a large number of years since last exposure. In accordance with other studies,5,11,17,18 hands were the most frequently involved skin area (accounting for 52% of our patients sensitized to epoxy resins), especially for occupational dermatitis. Epoxy resins are powerful sensitizers, often causing a severe allergic contact dermatitis, not only involving the hands but also other body surfaces (e.g. the face),17 both by direct and indirect contact. The face may be involved primarily through airborne exposure,2 accounting for 18.9% of epoxy resin sensitization in our sample. This was not a statistically significant difference from the control group. We noted several correlations between epoxy resins sensitization and profession, finding a significant relationship for both genders employed as mechanics, woodworkers, and chemical industry workers. Within the male cohort, there were correlations for farmers,
Discussion This study investigated the prevalence of epoxy resins sensitization with suspected allergic contact dermatitis, patch tested during 1996–2010 in Northeastern Italy using a database with 19 088 consecutive subjects. The overall prevalence of epoxy resins sensitization, from 1996 to 2010, was 0.64% in female and 1.39% in male subjects (overall combined prevalence 0.89%), which has remained relatively stable over time. These findings are slightly lower with respect to other European and American studies, which reported an overall prevalence ranging from 1 to 12.1%,4,5,10–13 but is in line with other studies14,15 and data from the Information Network of Departments of Dermatology in Germany (overall prevalence: 0.9– 1.4%; women 0.6–1.2%; men 1.6–2.3%) in patients patch tested from 1992 to 2000.16 The prevalence was relatively stable between age categories (divided into quintile), with the only
Table 2 Association between body area and epoxy resin sensitization Females Site
Pos
Hand Leg Face Other
28 2 15 16
% 45.90 3.28 24.59 26.23
Males
OR (95% CI)
Pos
1.33 (0.8–2.2) 0.47 (0.1–1.9) 1.1 (0.6–2) 0.76 (0.4–1.3)
38 2 9 17
% 57.58 3.03 13.64 25.76
Total
OR (95% CI) 1.82 0.28 1.09 0.65
(1.1–3.0) (0.1–1.1) (0.5–2.2) (0.4–1.1)
Pos
%
66 4 24 33
51.97 3.15 18.90 25.98
OR (95% CI) 1.61 0.38 0.96 0.72
(1.1–2.3) (0.1–1.0) (0.6–1.5) (0.5–1.1)
Reference category: subjects negative to epoxy resins Pos: number of positive subjects to epoxy resins. Percentages are related to the proportion of subjects affected by epoxy resins sensitization in each body area.
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fishermen, and construction workers. There was also a correlation between female artisans and epoxy resins sensitization. Several of these associations (such as construction workers, mechanics and wood processors) have been confirmed by other studies.4,14,19 We found a statistically significant increase in sensitization to epoxy resins for construction workers, from 1.4% in the 1996–1998 to 14.8% in 2008–2010. The important role of epoxy resins in this professional category is confirmed by previous studies,17,19,20 however, our findings confirm the prevalence of this sensitization is increasing in the building trade. A similar finding was reported by Geier1 in a cohort of 1153 construction workers affected by occupational contact dermatitis between 1994 and 2008. Geier reported that construction workers who started after 1999 had a significantly higher risk of sensitization to epoxy resins than those who started in 1999 or earlier. This study reported an alarming increase in epoxy resins sensitization in the building trade, which increased from 8.4 to 12.4%. We found a high prevalence of epoxy sensitization in painters (15% in males, 12.1% overall), but as our sample size was too small to acquire statistical significance, we included them in the ‘‘construction workers’’ category. However, these results are confirmed by other authors: Bock,17 Bangsgaard,4 and Mose21 all reported the relevant role of epoxy resins in painters. We found a statistically significant association between epoxy sensitization and unemployed males, possibly due to unreported exposures from hobbies, small repairs, or other undeclared activities. Former epoxy products users may also represent patients in this category. There are studies reporting statistical association with concomitant patch test reactions to epoxy resins and fragrance mix.22 In our study, we did not find a statistically significant association between those two haptens (OR 1.3, 95% CI 0.8–2.4), even when considering the sexes independently. The objective of this study was to investigate the prevalence of epoxy resin sensitization by occupational category in a large database of patients from
Northeastern Italy and to compare our results with available literature data. In Northeastern Italy, we found a low overall prevalence of sensitization with respect to other European and American studies, confirming the important role of epoxy resins exposures in some occupational categories (construction workers, mechanics, and wood workers). We also found associations for other occupational sectors including farming, fishing, and the chemical industry. This is one of the few studies to consider time trends in epoxy resins sensitization, confirming a considerable increase of prevalence in construction workers in Northeastern Italy, despite the increased attention to contact dermatitis in recent years. Nevertheless, this study had limitations. Although we analyzed a large sample of individuals, the study population was derived from patients who attended health services for suspected allergic dermatitis, and for this reason, our results may be affected by selection bias. However, this is minimized by the large population sample we analyzed and by the fact that all subjects were enrolled in the same way. Our results may also be affected by the healthy worker effect (which may have led to some decrease in the strength of association, and may partially explain the association we found in unemployed males – as part of this sample may be composed of people who retired from their work due to previous sensitization to epoxy resins). The merging of smaller groups into larger ones – due to statistical limitations of small group analysis – may also have led to some loss of data, which was the case for painters, as discussed above. Another possible limitation of this study is related to its multi-center design, as there have been differences in data collection and recording in different centers, although all participants accepted a standardized protocol. Another potential source of bias may depend on the referral nature of the practice, which can lead to underreporting of this clinical condition. We may assume, however, that underreporting in large samples, within close time periods, can lead realistically to
Table 3 Multiple regression analysis for the association between epoxy resins sensitization and occupation (reference category white-collar workers) Males Job White-collar workers Farmers and fishers Construction workers Mechanics Woodworkers Other artisans Chemical industry workers Unemployed
Females
%Pos.
OR
95% CI
%Pos.
0.73 2.75 3.66 1.79 2.76 2.00 3.30 3.16
1 3.88 5.2 2.48 3.87 2.79 4.64 4.44
(1.04–14.4) (2.4–11.2) (1.03–6.0) (1.2–12.5) (0.8–10.3) (1.3–17.2) (1.2–16.5)
0.53 0 0.92 2.17 2.31 1.79 2.70 0
Only statistically significant data are reported.
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OR
95% CI
1 1.73 4.13 4.41 3.4 5.18
(0.5–6.0) (1.6–10.6) (1.3–15.3) (1.3–8.8) (1.2–23)
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a non-differential bias, especially when sensibilization campaigns or similar initiatives have not been widely presented to the general population. Our study showed that although epoxy resins sensitization in Northeast Italy has remained relatively stable over the years analyzed, some professions were at higher risk of developing skin disease due to this exposure, particularly on their hands. This increased sensitization in some occupations is a call to action for increased study and prevention. Our data, in combination with results from other countries, suggest that replacement of epoxy resins with less sensitizing substances should be implemented whenever possible. In those contexts, in which this is not possible, proper training and information of working personnel on the risk and safer handling procedures should be mandatory. Workers should be provided with technical equipment and protective devices. The number of workers exposed to this sensitizing agent should be kept as low as reasonably possible.
Disclaimer Statement Contributor All authors belong to institutions members of North – East Italy Contact Dermatitis Group (NEICDG). All authors contributed in study design. A. Prodi wrote the article draft, cooperated in the preparation of the final database, performed the statistical analysis. F. Rui analyzed the data, revised the paper, and monitored data collection and performed a part of it (Trieste area). A. Belloni Fortina coordinated data collection in Padua area and revised the paper. M. T. Corradin coordinated data collection in Pordenone area and revised the paper. F. Larese Filon as coordinator of the NEICDS, coordinated data collection for the whole study, prepared the database and statistical analysis design, analyzed the data, and revised the paper. Funding No specific funding has been required or granted for this study. Conflict of interest The authors have no conflict of interest to declare. Ethics approval No experiments on healthy volunteers, patients or animals: all subjects were recruited from a database of patients that underwent patch test for diagnostic purposes.
Acknowledgements We acknowledge all centers member of the Northeast Italy Contact Dermatitis Group (NEICDG): Dermatologic Unit S. Chiara Hospital (Trento), Dermatologic Unit Hospital of Rovigo, Dermatologic
Occupational sensitization to epoxy resins in northeastern Italy
Unit S. Martino Hospital (Belluno), Dermatologic Unit Poliambulatorio Euganea Medica (Padua).
References 1 Geier J, Krautheim A, Uter W, Lessmann H, Schnuch A. Occupational contact allergy in the building trade in Germany: influence of preventive measures and changing exposure. Int Arch Occup Environ Health. 2011;84:403–11. 2 Machado S, Silva E, Sanches M, Massa A. Occupational airborne contact dermatitis. Am J Contact Dermaitis. 2003;14:31–2. 3 Ge´raut C. L’essentiel des pathologies professionnelles. Paris: Ellipses; 1995. 4 Bangsgaard N, Thyssen JP, Menne´ T, Andersen KE, Mortz CG, Paulsen E, et al. Contact allergy to epoxy resin: risk occupations and consequences. Contact Dermatitis. 2012;67(2):73–7. 5 Amado A, Taylor J. Contact allergy to epoxy resins. Contact Dermatitis. 2008;5:186–7. 6 Bjorkner B, Pote´n A, Zimerson E, Frick M. Contact Dermatitis, 4th edn. Berlin: Springer-Verlag; 2006. p. 597. 7 Rui F, Bovenzi M, Prodi A, Fortina AB, Romano I, Peserico A, et al. Nickel, cobalt and chromate sensitization and occupation. Contact Dermatitis. 2010;62:225–31. 8 Isaksson M, Branda˜o F, Bruze M, Goossens A. Recommendation to include budesonide and tixocortol pivalate in the European standard series. Contact Dermatitis. 2000;43:41–2. 9 Wilkinson DS, Fregert S, Magnusson M, Bandmann HJ, Calnan CD, Cronin E, et al. Terminology of contact dermatitis. Acta Derm Venereol. 1970;50:287–92. 10 Romyhr O, Nyfors A, Leira H, Smedbold H. Allergic contact dermatitis caused by epoxy resin systems in industrial painters. Contact Dermatitis. 2006;55:167–72. 11 Cahill J, Keegel T, Dharmage S, Nugriaty D. Prognosis of contact dermatitis in epoxy resin workers. Contact Dermatitis. 2006;55:167–72. 12 Rietschel R, Mathias C, Fowler JJ Jr., Pratt M, Taylor JS, Sherertz EF, et al. Relationship of occupation to contact dermatitis: evaluation in patients tested from 1998 to 2000. Am J Contact Dermat. 2002;13:170–6. 13 Cherry N, Meyer J, Adisesh A, Brooke R, Owen-Scmith V, Swales C, et al. Surveillance of occupational skin disease: EPIDERM and OPRA. Br J Dermatol. 2000;142:1128–34. 14 Canelas M, Gonc¸alo M, Figueiredo A. Contact allergy to epoxy resins 2 a 10-year study. Contact Dermatitis. 2010;62:55. 15 Majasuo S, Liipo J, Lammintausta K. Non-occupational contact sensitization to epoxy resin of bisphenol A among general dermatology patients. Contact Dermatitis. 2011;66:148–53. 16 Geier J, Uter W, Lessmann H, Hillen U, Goergens U, Kersting K et al. Kontaktallergien gegen Epoxidharze – ein unterdiagnostiziertes Problem. Allergo J. 2003;12:323–8. 17 Bock M, Schmidt A, Bruckner T, Diepgen T. Occupational skin disease in the construction industry. Br J Dermatol. 2003;149:1165–71. 18 Geier J, Lessmann H, Hillen U, Jappe U, Dickel H, Koch P, et al. An attempt to improve diagnostics of contact allergy due to epoxy resin systems. First results of the multicentre study EPOX 2002. Contact Dermatitis. 2004;51:263–72. 19 Dickel H, Kuss O, Schmidt A, Diepgen T. Occupational relevance of positive standard patch test results in employed persons with an initial report of an occupational skin disease. Int Arch Occup Environ Health. 2002;75:423–34. 20 Uter W, Ru¨hl R, Pfahlberg A, Geier J, Schnuch A, Gefeller O. Contact allergy in construction workers: results of a multifactorial analysis. Ann Occup Hyg. 2004;48(1):21–7. 21 Mose A, Lundov M, Zachariae C, Menne´ T, Veien NK, Laurberg G, et al. Occupational contact dermatitis in painters: an analysis of patch test data from the Danish Contact Dermatitis Group. Contact Dermatitis. 2012;67(5):293–7. 22 Andersen K, Christensen L, Vølund A, Johansen J, Paulsen E. Association between positive patch tests to epoxy resin and fragrance mix I ingredients. Contact Dermatitis. 2009;60:155–7. 23 Geraut C, Tripodi D, Brunet-Courtois B, Leray C, Geraut L. Occupational dermatitis to epoxydic and phenolic resins. Eur J Dermatol. 2009;3(19):205–13.
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Clinical Unit of Occupational Medicine, University of Trieste, Italy, 2Dermatology Unit, Department of Pediatrics, University of Padua, Italy, 3Dermatology Unit, S. Maria degli Angeli Hospital, Pordenone, Italy Background: One of the main health concerns of epoxy resins is their role as skin sensitizer. This sensitization is not uncommon, because the prevalence ranges around 1–12% of the general population. Objectives: Perform a cross sectional study in a patch test population from Northeastern Italy to investigate the prevalence of epoxy resins sensitization among patients with suspected contact dermatitis. Subsequently, relate findings to patients’ occupation and evaluate time trend of prevalence. Methods: The final study database included 19 088 consecutive patients, tested from 1996 to 2010 in Northeastern Italy. Results: The overall prevalence of epoxy resins sensitization was 0.89%. Dermatitis most frequently involved hands (40.25%). In both sexes, we find a significant correlation in mechanics, woodworkers, and chemical industry workers; and in males only, among farmers and fishers, construction workers, and unemployed. We found significant increase of sensitization in construction workers in the analyzed period. Conclusions: The overall prevalence of sensitization to epoxy resins in Northeastern Italy is in line with other European countries, but we found an increased risk of sensitization in some professions and an increasing trend of prevalence in construction workers. Better preventive actions are strongly advised in higher risk professions, with particular attentions towards building sector.
Keywords: Epoxy resins, Patch test, Allergic contact dermatitis, Epidemiology
Introduction Occupational contact dermatitis to epoxy resins is an important health concern due to the wide diffusion of products containing this powerful hapten. Sensitization is often acquired after a short exposure time1 when workers are exposed to unhardened epoxy resin. Dermatitis predominantly occurs on the hands but can also involve the face. The primary route of exposure is airborn.2 Clinical manifestations can involve exposed and unexposed skin with important skin reactions that can cause sick leave, ill health retirement, or job changing in affected workers. Epoxy resins are a class of ubiquitous chemicals, polymers, and reactive prepolymers, which contain epoxide groups, widely used for their exceptional properties of hardness and impact resistance to heat, water, and chemicals, as well as their abilities to function as electric insulators and adhesives.3 A wide array of applications use epoxy-based materials including adhesives, composite materials (carbon Correspondence to: Andrea Prodi, Unita` Clinica Operativa di Medicina del Lavoro, Dipartimento di Scienze Medico Chirurgiche e della Salute, Universita` degli Studi di Trieste, Centro Tumori – Via della Pieta`, 19 Trieste I-34129, Italy. Email: [email protected]
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fiber, fiberglass reinforcements), paintings and coatings, industrial tooling and composites, electrical systems and electronics, consumers and marine applications, the aerospace industry, and biology. Seventy-five to ninety percent of epoxy resins are based on epichlorohydrin and bisphenol A, which react to form diglycidylether of bisphenol A (DGEBA). The diglycidyl ether of bisphenol F (DGEBF) is the base of approximately 1% of epoxy resins.4 Epoxy resins systems (epoxy monomer, hardener, reactive diluent, and/or other additives) may pose health hazards in the occupational environment during the production or use of resins.5 Diglycidylether of bisphenol A is a sensitizer for approximately 60–80% of patients with allergic contact dermatitis to epoxy resins.6 Sensitization may occur in unhardened epoxy resin handlers, while fully cured epoxy resin is non-irritating and nonsensitizing4 (although some traces of epoxy monomers may still be present due to an incomplete curing). This study investigated the prevalence of epoxy resins sensitization in a population from Northeastern Italy, evaluated between 1996 and 2010, (1) in order to
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analyze for temporal trend of this sensitization, (2) to find out whether it was stable over time in the overall population, (3) as well as by occupational category, and (4) to investigate for associations between epoxy resins sensitization and occupations in a geographical context.
Methods Study subjects From 1996 to 2010, 19 666 consecutive patients with symptoms and/or signs of suspected allergic dermatitis were patch tested in eight departments of dermatology or occupational medicine in Northeastern Italy (Belluno, Bolzano, Padua, Pordenone, Rovereto, Rovigo, Trento, and Trieste). Individual characteristics, occupational history, and personal and family history of atopy (asthma and/or allergic rhino-conjunctivitis with at least one positive prick test reaction to relevant aeroallergens) were collected through a standardized questionnaire.7 After excluding 578 patients for missing data (related to personal history – e.g. sex or age – or incomplete patch testing), 19 088 consecutive subjects were included in the analysis. All subjects were affected by dermatitis, most of them with moderate/severe reactions. All subjects were categorized by occupation, collapsing related job groups into larger ones (e.g. nurses, physicians, and other hospital workers were collapsed into the ‘‘health care workers’’ category). Similarly, body site categories were collapsed (e.g. fingers, palm, and dorsum hands were collapsed into ‘‘hands’’). We performed occupational category related analysis on 16 267 subjects, discarding 3399 because of the incomplete or inaccurate collection of subject’s occupational anamnesis. Exposure was estimated based on the subject’s current profession. Because sensitization is often acquired after a short exposure,1 we did not take into account historical occupational anamnesis but instead, only the subject’s job at the time of evaluation Subjects was classified by profession, and statistical analyses were stratified by sex and age differences to minimize confounding (described below). All patients provided written informed consent.
Patch tests Finn ChambersH on ScanporH (Epitest Ltd, Tuusula, Finland) and allergens from FIRMA (Firenze, Italy) were used to patch test patients with the European baseline series.8 The tested allergens included epoxy resins (Araldite 1% in pet). Patches were applied on the upper back and removed after 48 hours. The sites were examined on removal and 24 or 48 hours after removal, according to International Contact Dermatitis Research Group guidelines.9 Reactions of grades z, zz, and zzz in the second examination were considered to be
Occupational sensitization to epoxy resins in northeastern Italy
positive. Dubious or nebulous reactions (¡, ‘‘?’’) were considered negative.
Statistical analysis Data analysis was performed using STATA v. 12.0 software (Stata Corp., LP, College Station, TX, USA). Categorical data were cross-tabulated into k6k contingency tables. The associations between patch test results, patient age (quintiles: #25, 26–34, 35–44, 45–57, and §58 years), year of patch testing (according to 3-year calendar periods: 1996–1998, 1999–2001, 2002–2004, 2005–2007, 2008–2010), and occupation were investigated using multivariate logistic regression analysis. Odds ratios and 95% confidence intervals were estimated from the coefficients and the standard errors of logistic regression output. Logistic analysis was conducted separately by gender, adjusting results by age, with white-collar workers as the reference group (we can assume that epoxy resins sensitization in this professional group is likely non-occupationally related). Trend tests across ordered groups were performed using Cuzick’s test for trend. Patients with missing data were excluded from the analysis. A P-value of ,0.05 was used to denote statistical significance.
Results The study population included 12 820 women (67.2%) and 6268 men (32.8%). The overall prevalence of epoxy resin sensitization was 0.89% (0.64% of women and 1.39% of men). Table 1 shows the distribution of professions within the study population by sex. In this table, we considered 16 267 patients [10 989 females (67.6%) and 5278 males (32.4%)], excluding the remaining patients because of incomplete or inaccurate determination of job category. For both sexes, the prevalence of epoxy resins sensitization remained relatively stable during the study, without showing any statistically significant variation (Fig. 1) (P-value for trend: females P50.435, males P50.461). The prevalence was rather homogeneous among the considered age quintiles (P-values for trend: females P50.924, males P50.122), with the only exception in males over 58 years old (fifth quintile). The prevalence in this age group was less than half of the average prevalence in males (0.53%), a statistically significant difference (P50.013) (Fig. 2). Dermatitis most frequently involved hands (40.25% for all patients and 51.97% for patients sensitized to epoxy resins). In Table 2, we compared subjects’ positive for epoxy resins sensitization to subjects negative for epoxy resins (by sex). Among males, hands were more frequently sensitized to epoxy resins (57.58%) compared to subjects without sensitization for this body area; the statistically significant
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Figure 1 Prevalence of sensitization to epoxy resins, by sex, from 1996 to 2010.
difference being (OR 1.82, 95% CI 1.1–3.0). No other body site showed a statistically significant association. Table 3 reports the results of multinomial logistic regression analysis, adjusted by age, investigating for an association between sensitization to epoxy resins and occupation. For both sexes, we found a significant association to sensitization for mechanics (males: OR 2.48, 95% CI 1.03–6; females: OR 4.13, 95% CI 1.6–10.6), woodworkers (males: OR 3.87, 95% CI 1.2–12.5; females: OR 4.41, 95% CI 1.3–15.3), and chemical industry workers (males: OR 4.64, 95%
CI 1.3–17.2; females: OR 5.18, 95% CI 1.2–23). In males, we found a significant association for farmers and fishers (OR 3.88, 95% CI 1.04–14.4), construction workers (OR 5.2, 95% CI 2.4–11.2), and the unemployed (OR 4.44, 95% CI 1.2–16.5). For construction workers, we found a significant increase in sensitization over time from 1.4% (in 1996–1998 period) to 14.8% (in 2008–2010) (P50.004). Painters (20 males, 13 females) also had a high prevalence of sensitization to epoxy resins. We identified four subjects (12.1%) sensitized to resins, three males and
Table 1 Occupational categories of the study population Gender Job White-collar workers1 Household workers Retired Healthcare workers Construction workers Mechanics Maids and restaurant workers Other artisans Other occupations Unemployed Woodworkers Barbers, hairdressers Professional drivers Domestic workers Farmers and fishers Chemical industry workers Paper production workers Mechanical machines workers Upholsterers Total
Females 3003 2411 1327 1708 327 277 499 335 164 205 130 191 31 181 78 74 19 20 9
%
Males
%
Total
%
27.33 21.94 12.08 15.54 2.98 2.52 4.54 3.05 1.49 1.87 1.18 1.74 0.28 1.65 0.71 0.67 0.17 0.18 0.08
1369 28 1015 486 573 559 255 150 140 95 145 18 175 23 109 91 27 19 1
25.94 0.53 19.23 9.21 10.86 10.59 4.83 2.84 2.65 1.80 2.75 0.34 3.32 0.44 2.07 1.72 0.51 0.36 0.02
4372 2439 2342 2194 900 836 754 485 304 300 275 209 206 204 187 165 46 39 10
26.88 14.99 14.40 13.49 5.53 5.14 4.64 2.98 1.87 1.84 1.69 1.28 1.27 1.25 1.15 1.01 0.28 0.24 0.06
10 989
5278
16 267
1
White-collar workers: this group is primarily composed of clerks, but professors and students also are included.
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Figure 2 Prevalence of sensitization to epoxy resins, by sex, within considered age quintiles.
one female. However, given the small subsample, we included painters within the ‘‘construction worker’’ category.
exception in males older than 57 years (0.53%). This may be explained by the limited use of epoxy resins in the past, contributing to a lower exposure dose or reflect a decrease in sensitization because of a large number of years since last exposure. In accordance with other studies,5,11,17,18 hands were the most frequently involved skin area (accounting for 52% of our patients sensitized to epoxy resins), especially for occupational dermatitis. Epoxy resins are powerful sensitizers, often causing a severe allergic contact dermatitis, not only involving the hands but also other body surfaces (e.g. the face),17 both by direct and indirect contact. The face may be involved primarily through airborne exposure,2 accounting for 18.9% of epoxy resin sensitization in our sample. This was not a statistically significant difference from the control group. We noted several correlations between epoxy resins sensitization and profession, finding a significant relationship for both genders employed as mechanics, woodworkers, and chemical industry workers. Within the male cohort, there were correlations for farmers,
Discussion This study investigated the prevalence of epoxy resins sensitization with suspected allergic contact dermatitis, patch tested during 1996–2010 in Northeastern Italy using a database with 19 088 consecutive subjects. The overall prevalence of epoxy resins sensitization, from 1996 to 2010, was 0.64% in female and 1.39% in male subjects (overall combined prevalence 0.89%), which has remained relatively stable over time. These findings are slightly lower with respect to other European and American studies, which reported an overall prevalence ranging from 1 to 12.1%,4,5,10–13 but is in line with other studies14,15 and data from the Information Network of Departments of Dermatology in Germany (overall prevalence: 0.9– 1.4%; women 0.6–1.2%; men 1.6–2.3%) in patients patch tested from 1992 to 2000.16 The prevalence was relatively stable between age categories (divided into quintile), with the only
Table 2 Association between body area and epoxy resin sensitization Females Site
Pos
Hand Leg Face Other
28 2 15 16
% 45.90 3.28 24.59 26.23
Males
OR (95% CI)
Pos
1.33 (0.8–2.2) 0.47 (0.1–1.9) 1.1 (0.6–2) 0.76 (0.4–1.3)
38 2 9 17
% 57.58 3.03 13.64 25.76
Total
OR (95% CI) 1.82 0.28 1.09 0.65
(1.1–3.0) (0.1–1.1) (0.5–2.2) (0.4–1.1)
Pos
%
66 4 24 33
51.97 3.15 18.90 25.98
OR (95% CI) 1.61 0.38 0.96 0.72
(1.1–2.3) (0.1–1.0) (0.6–1.5) (0.5–1.1)
Reference category: subjects negative to epoxy resins Pos: number of positive subjects to epoxy resins. Percentages are related to the proportion of subjects affected by epoxy resins sensitization in each body area.
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fishermen, and construction workers. There was also a correlation between female artisans and epoxy resins sensitization. Several of these associations (such as construction workers, mechanics and wood processors) have been confirmed by other studies.4,14,19 We found a statistically significant increase in sensitization to epoxy resins for construction workers, from 1.4% in the 1996–1998 to 14.8% in 2008–2010. The important role of epoxy resins in this professional category is confirmed by previous studies,17,19,20 however, our findings confirm the prevalence of this sensitization is increasing in the building trade. A similar finding was reported by Geier1 in a cohort of 1153 construction workers affected by occupational contact dermatitis between 1994 and 2008. Geier reported that construction workers who started after 1999 had a significantly higher risk of sensitization to epoxy resins than those who started in 1999 or earlier. This study reported an alarming increase in epoxy resins sensitization in the building trade, which increased from 8.4 to 12.4%. We found a high prevalence of epoxy sensitization in painters (15% in males, 12.1% overall), but as our sample size was too small to acquire statistical significance, we included them in the ‘‘construction workers’’ category. However, these results are confirmed by other authors: Bock,17 Bangsgaard,4 and Mose21 all reported the relevant role of epoxy resins in painters. We found a statistically significant association between epoxy sensitization and unemployed males, possibly due to unreported exposures from hobbies, small repairs, or other undeclared activities. Former epoxy products users may also represent patients in this category. There are studies reporting statistical association with concomitant patch test reactions to epoxy resins and fragrance mix.22 In our study, we did not find a statistically significant association between those two haptens (OR 1.3, 95% CI 0.8–2.4), even when considering the sexes independently. The objective of this study was to investigate the prevalence of epoxy resin sensitization by occupational category in a large database of patients from
Northeastern Italy and to compare our results with available literature data. In Northeastern Italy, we found a low overall prevalence of sensitization with respect to other European and American studies, confirming the important role of epoxy resins exposures in some occupational categories (construction workers, mechanics, and wood workers). We also found associations for other occupational sectors including farming, fishing, and the chemical industry. This is one of the few studies to consider time trends in epoxy resins sensitization, confirming a considerable increase of prevalence in construction workers in Northeastern Italy, despite the increased attention to contact dermatitis in recent years. Nevertheless, this study had limitations. Although we analyzed a large sample of individuals, the study population was derived from patients who attended health services for suspected allergic dermatitis, and for this reason, our results may be affected by selection bias. However, this is minimized by the large population sample we analyzed and by the fact that all subjects were enrolled in the same way. Our results may also be affected by the healthy worker effect (which may have led to some decrease in the strength of association, and may partially explain the association we found in unemployed males – as part of this sample may be composed of people who retired from their work due to previous sensitization to epoxy resins). The merging of smaller groups into larger ones – due to statistical limitations of small group analysis – may also have led to some loss of data, which was the case for painters, as discussed above. Another possible limitation of this study is related to its multi-center design, as there have been differences in data collection and recording in different centers, although all participants accepted a standardized protocol. Another potential source of bias may depend on the referral nature of the practice, which can lead to underreporting of this clinical condition. We may assume, however, that underreporting in large samples, within close time periods, can lead realistically to
Table 3 Multiple regression analysis for the association between epoxy resins sensitization and occupation (reference category white-collar workers) Males Job White-collar workers Farmers and fishers Construction workers Mechanics Woodworkers Other artisans Chemical industry workers Unemployed
Females
%Pos.
OR
95% CI
%Pos.
0.73 2.75 3.66 1.79 2.76 2.00 3.30 3.16
1 3.88 5.2 2.48 3.87 2.79 4.64 4.44
(1.04–14.4) (2.4–11.2) (1.03–6.0) (1.2–12.5) (0.8–10.3) (1.3–17.2) (1.2–16.5)
0.53 0 0.92 2.17 2.31 1.79 2.70 0
Only statistically significant data are reported.
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OR
95% CI
1 1.73 4.13 4.41 3.4 5.18
(0.5–6.0) (1.6–10.6) (1.3–15.3) (1.3–8.8) (1.2–23)
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a non-differential bias, especially when sensibilization campaigns or similar initiatives have not been widely presented to the general population. Our study showed that although epoxy resins sensitization in Northeast Italy has remained relatively stable over the years analyzed, some professions were at higher risk of developing skin disease due to this exposure, particularly on their hands. This increased sensitization in some occupations is a call to action for increased study and prevention. Our data, in combination with results from other countries, suggest that replacement of epoxy resins with less sensitizing substances should be implemented whenever possible. In those contexts, in which this is not possible, proper training and information of working personnel on the risk and safer handling procedures should be mandatory. Workers should be provided with technical equipment and protective devices. The number of workers exposed to this sensitizing agent should be kept as low as reasonably possible.
Disclaimer Statement Contributor All authors belong to institutions members of North – East Italy Contact Dermatitis Group (NEICDG). All authors contributed in study design. A. Prodi wrote the article draft, cooperated in the preparation of the final database, performed the statistical analysis. F. Rui analyzed the data, revised the paper, and monitored data collection and performed a part of it (Trieste area). A. Belloni Fortina coordinated data collection in Padua area and revised the paper. M. T. Corradin coordinated data collection in Pordenone area and revised the paper. F. Larese Filon as coordinator of the NEICDS, coordinated data collection for the whole study, prepared the database and statistical analysis design, analyzed the data, and revised the paper. Funding No specific funding has been required or granted for this study. Conflict of interest The authors have no conflict of interest to declare. Ethics approval No experiments on healthy volunteers, patients or animals: all subjects were recruited from a database of patients that underwent patch test for diagnostic purposes.
Acknowledgements We acknowledge all centers member of the Northeast Italy Contact Dermatitis Group (NEICDG): Dermatologic Unit S. Chiara Hospital (Trento), Dermatologic Unit Hospital of Rovigo, Dermatologic
Occupational sensitization to epoxy resins in northeastern Italy
Unit S. Martino Hospital (Belluno), Dermatologic Unit Poliambulatorio Euganea Medica (Padua).
References 1 Geier J, Krautheim A, Uter W, Lessmann H, Schnuch A. Occupational contact allergy in the building trade in Germany: influence of preventive measures and changing exposure. Int Arch Occup Environ Health. 2011;84:403–11. 2 Machado S, Silva E, Sanches M, Massa A. Occupational airborne contact dermatitis. Am J Contact Dermaitis. 2003;14:31–2. 3 Ge´raut C. L’essentiel des pathologies professionnelles. Paris: Ellipses; 1995. 4 Bangsgaard N, Thyssen JP, Menne´ T, Andersen KE, Mortz CG, Paulsen E, et al. Contact allergy to epoxy resin: risk occupations and consequences. Contact Dermatitis. 2012;67(2):73–7. 5 Amado A, Taylor J. Contact allergy to epoxy resins. Contact Dermatitis. 2008;5:186–7. 6 Bjorkner B, Pote´n A, Zimerson E, Frick M. Contact Dermatitis, 4th edn. Berlin: Springer-Verlag; 2006. p. 597. 7 Rui F, Bovenzi M, Prodi A, Fortina AB, Romano I, Peserico A, et al. Nickel, cobalt and chromate sensitization and occupation. Contact Dermatitis. 2010;62:225–31. 8 Isaksson M, Branda˜o F, Bruze M, Goossens A. Recommendation to include budesonide and tixocortol pivalate in the European standard series. Contact Dermatitis. 2000;43:41–2. 9 Wilkinson DS, Fregert S, Magnusson M, Bandmann HJ, Calnan CD, Cronin E, et al. Terminology of contact dermatitis. Acta Derm Venereol. 1970;50:287–92. 10 Romyhr O, Nyfors A, Leira H, Smedbold H. Allergic contact dermatitis caused by epoxy resin systems in industrial painters. Contact Dermatitis. 2006;55:167–72. 11 Cahill J, Keegel T, Dharmage S, Nugriaty D. Prognosis of contact dermatitis in epoxy resin workers. Contact Dermatitis. 2006;55:167–72. 12 Rietschel R, Mathias C, Fowler JJ Jr., Pratt M, Taylor JS, Sherertz EF, et al. Relationship of occupation to contact dermatitis: evaluation in patients tested from 1998 to 2000. Am J Contact Dermat. 2002;13:170–6. 13 Cherry N, Meyer J, Adisesh A, Brooke R, Owen-Scmith V, Swales C, et al. Surveillance of occupational skin disease: EPIDERM and OPRA. Br J Dermatol. 2000;142:1128–34. 14 Canelas M, Gonc¸alo M, Figueiredo A. Contact allergy to epoxy resins 2 a 10-year study. Contact Dermatitis. 2010;62:55. 15 Majasuo S, Liipo J, Lammintausta K. Non-occupational contact sensitization to epoxy resin of bisphenol A among general dermatology patients. Contact Dermatitis. 2011;66:148–53. 16 Geier J, Uter W, Lessmann H, Hillen U, Goergens U, Kersting K et al. Kontaktallergien gegen Epoxidharze – ein unterdiagnostiziertes Problem. Allergo J. 2003;12:323–8. 17 Bock M, Schmidt A, Bruckner T, Diepgen T. Occupational skin disease in the construction industry. Br J Dermatol. 2003;149:1165–71. 18 Geier J, Lessmann H, Hillen U, Jappe U, Dickel H, Koch P, et al. An attempt to improve diagnostics of contact allergy due to epoxy resin systems. First results of the multicentre study EPOX 2002. Contact Dermatitis. 2004;51:263–72. 19 Dickel H, Kuss O, Schmidt A, Diepgen T. Occupational relevance of positive standard patch test results in employed persons with an initial report of an occupational skin disease. Int Arch Occup Environ Health. 2002;75:423–34. 20 Uter W, Ru¨hl R, Pfahlberg A, Geier J, Schnuch A, Gefeller O. Contact allergy in construction workers: results of a multifactorial analysis. Ann Occup Hyg. 2004;48(1):21–7. 21 Mose A, Lundov M, Zachariae C, Menne´ T, Veien NK, Laurberg G, et al. Occupational contact dermatitis in painters: an analysis of patch test data from the Danish Contact Dermatitis Group. Contact Dermatitis. 2012;67(5):293–7. 22 Andersen K, Christensen L, Vølund A, Johansen J, Paulsen E. Association between positive patch tests to epoxy resin and fragrance mix I ingredients. Contact Dermatitis. 2009;60:155–7. 23 Geraut C, Tripodi D, Brunet-Courtois B, Leray C, Geraut L. Occupational dermatitis to epoxydic and phenolic resins. Eur J Dermatol. 2009;3(19):205–13.
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