Andrea 't Mannetje

Occupation and bladder cancer among men in Western Europe

Objectives: We examined which occupations and industries are currently at high risk for bladder cancer in men. Methods: We combined data from 11 case–control studies conducted between 1976–1996 in six European countries. The study comprised 3346 incident cases and 6840 controls, aged 30–79 years. Lifetime occupational and smoking histories were examined using common coding. Results: Odds ratios for eight a priori defined high-risk occupations were low, and with the exception of metal workers and machinists (OR = 1.16, 95% CI = 1.02–1.32), were not statistically significant. Higher risks were observed for specific categories of painters, metal, textile and electrical workers, for miners, transport operators, excavating-machine operators, and also for non-industrial workers such as concierges and janitors. Industries entailing a high risk included salt mining, manufacture of carpets, paints, plastics and industrial chemicals. An increased risk was found for exposure to PAHs (OR for highest exposure tertile = 1.23, 95% CI = 1.07–1.4). The risk attributable to occupation ranged from 4.2 to 7.4%, with an estimated 4.3% for exposure to PAHs. Conclusions: Metal workers, machinists, transport equipment operators and miners are among the major occupations contributing to occupational bladder cancer in men in Western Europe. In this population one in 10 to one in 20 cancers of the bladder can be attributed to occupation.

Pooled exposure–response analyses and risk assessment for lung cancer in 10 cohorts of silica-exposed workers: an IARC multicentre study

AbstractObjectives: Silica is one of the most common occupational exposures worldwide. In 1997 the International Agency for Research on Cancer (IARC) classified inhaled crystalline silica as a human carcinogen (group 1), but acknowledged limitations in the epidemiologic data, including inconsistencies across studies and the lack of extensive exposure–response data. We have conducted a pooled exposure–response analysis of 10 silica-exposed cohorts to investigate lung cancer. Methods: The pooled cohort included 65,980 workers (44,160 miners, 21,820 nominees), and 1072 lung cancer deaths (663 miners, 409 nonminers). Follow-up has been extended for five of these cohorts beyond published data. Quantitative exposure estimates by job and calendar time were adopted, modified, or developed to permit common analyses by respirable silica (mg/m3) across cohorts. Results: The log of cumulative exposure, with a 15-year lag, was a strong predictor of lung cancer (p = 0.0001), with consistency across studies (test for heterogeneity, p = 0.34). Results for the log of cumulative exposure were consistent between underground mines and other facilities. Categorical analyses by quintile of cumulative exposure resulted in a monotonic trend with odds ratios of 1.0, 1.0, 1.3, 1.5, 1.6. Analyses using a spline curve also showed a monotonic increase in risk with increasing exposure. The estimated excess lifetime risk (through age 75) of lung cancer for a worker exposed from age 20 to 65 at 0.1 mg/m3 respirable crystalline silica (the permissible level in many countries) was 1.1–1.7%, above background risks of 3–6%. Conclusions: Our results support the decision by the IARC to classify inhaled silica in occupational settings as a carcinogen, and suggest that the current exposure limits in many countries may be inadequate. These data represent the first quantitative exposure–response analysis and risk assessment for silica using data from multiple studies.

Occurrence of alternative flame retardants in indoor dust from New Zealand: Indoor sources and human exposure assessment

Due to worldwide restrictions on polybrominated diphenyl ethers (PBDEs), the demand for alternative flame retardants (AFRs), such as organophosphate flame retardants (OPFRs), novel brominated FRs (NBFRs) and hexabromocyclododecanes (HBCDs), has recently increased. Little is known about human exposure to NBFRs and OPFRs and that their levels in dust have been scarcely evaluated worldwide. To increase the knowledge regarding these chemicals, we measured concentrations of five major NBFRs, ten OPFRs and three HBCD isomers in indoor dust from New Zealand homes. Dust samples were taken from living room floors (n=34) and from mattresses of the same houses (n=16). Concentrations (ngg(-1)) of NBFRs were: 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) (<2-175), decabromodiphenyl ethane (DBDPE) (<5-1430), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) (<2-2285) and bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (TBPH) (<2-640). For OPFRs, concentrations (ngg(-1)) ranged between: tri-ethyl-phosphate (TEP) (<10-235), tri-n-butyl-phosphate (TnBP) (<20-7545), tris-(2-chloroethyl)-phosphate (TCEP) (<20-7605), tris-(1-chloro-2-propyl) phosphate (TCPP) (20-7615), tri-(2-butoxyethyl)-phosphate (TBEP) (50-27325), tris-(2,3-dichloropropyl)-phosphate (TDCPP) (20-16560), tri-phenyl-phosphate (TPhP) (20-35190), and tri-cresyl-phosphate (TCP) (<50-3760). HBCD concentrations fell in the range <2-4100ngg(-1). BTBPE, DBDPE, TBPH, TBEP, and TnBP showed significant positive correlation (p<0.05) between their concentrations in mattresses and the corresponding floor dust (n=16). These data were used to derive a range of plausible exposure scenarios. Although the estimated exposure is well below the corresponding reference doses (RfDs), caution is needed given the likely future increase in use of these FRs and the currently unknown contribution to human exposure by other pathways such as inhalation and diet.

Sinonasal cancer, occupation, and tobacco smoking in European women and men

BACKGROUND In this analysis of European case-control studies on sinonasal cancer, we examined the risk for occupation and smoking, by gender and histological type. METHODS The pooled data included 104 female and 451 male cases, and 241 female and 1,464 male controls. Lifetime smoking and occupational history were recoded following uniform criteria, and job-exposure matrices were applied for wood and leather dust. RESULTS Wood dust exposure was associated with an excess risk in men (OR = 2.36, 95% CI 1.75-3.2) but not in women (OR = 1.17, 95% CI 0.31-4.47). Exposure to leather dust was associated with an excess risk in both genders. Both wood and leather dust were associated with adenocarcinomas rather than squamous cell carcinomas. Excess risks for smoking were higher for squamous cell carcinomas and higher in men than in women. CONCLUSIONS In these European populations, occupation was associated with about 11% of all sinonasal cancers in women and 39% in men. This difference can, in part, be attributed to variation in exposure patterns between genders.

Assessing exposure misclassification by expert assessment in multicenter occupational studies

Background: In a multicenter case-control study of lung cancer in central and eastern Europe and in Liverpool, exposure to occupational agents was assessed by teams of local experts. We performed an interteam agreement study to estimate the levels of exposure misclassification and the expected attenuation of the risk estimate. Methods: Eight teams of experts and a reference rater assessed exposure to 70 putative lung carcinogens for 19 jobs. Agreement among teams was calculated through Cohen’s kappa, sensitivity, and specificity. Results: Each team showed an overall fair to good agreement with the reference (kappa between 0.53 and 0.64). The agreement among teams in the presence of exposure was excellent for 9 agents, fair to good for 16, and poor for 29. For all agents the specificity was high (average 0.94), although sensitivity varied considerably. Conclusions: This study of expert exposure assessment showed a small range in reliability among teams of experts, but large differences among agents. This paper presents the range in levels of misclassification that can be expected using experts for assessing occupational exposure to different agents, and the attenuation of the odds ratio that can be expected to result from this misclassification.

Comparison of exposure assessment methods for occupational carcinogens in a multi-centre lung cancer case–control study

Objectives Retrospective exposure assessment remains a problematic aspect of population-based case–control studies. Different methods have been developed, including case-by-case expert assessment and job–exposure matrices (JEM). The present analyses compare exposure prevalence and risk estimates derived by different exposure assessment methods. Methods In the context of a case–control study conducted in seven European countries, exposure was estimated for asbestos, diesel motor emissions (DME) and crystalline silica, using three different assessment methods. First, experts assigned exposures to all reported jobs on a case-by-case basis. Second, a population-specific JEM (PSJEM) was developed using the expert assessments of controls only, and re-applied to all study subjects. Third, an independent general population JEM (GPJEM) was created by occupational exposure experts not involved in the original study, and applied to study subjects. Results from these methods were compared. Results There was poor to fair agreement in assigned exposure between expert assessment and the GPJEM (kappas: asbestos 0.17; DME 0.48; silica 0.38). Exposure prevalence was significantly heterogeneous (p<0.01) between countries for all three agents and assessment methods. For asbestos and DME, significant country heterogeneity in risk estimates was observed when using expert assessment. When applying the GPJEM, the heterogeneity in risk estimates for asbestos and, to some extent, silica diminished. Conclusions It has been previously advocated that the expert assessment approach to assign exposures based on detailed questionnaire responses provides more accurate exposure estimates than JEM-based results. However, current results demonstrated little, if any, advantage of case-by-case assessment when compared to a JEM approach.

Exposure-response analysis and risk assessment for silica and silicosis mortality in a pooled analysis of six cohorts

Aims: To study the relation between exposure to crystalline silica and silicosis mortality. Although mortality is an important endpoint for regulators, there have been no exposure-response studies for silicosis mortality, because of the relative rareness of silicosis as an underlying cause of death, and the limited availability of quantitative exposure estimates. Methods: Data from six occupational cohorts were pooled with good retrospective exposure data in which 170 deaths from silicosis were reported. Standard life table analyses, nested case-control analyses, and risk assessment were performed. Results: The rate of silicosis mortality in the combined data was 28/100 000 py, increasing in nearly monotonic fashion from 4.7/100 000 for exposure of 0–0.99 mg/m3-years to 233/100 000 for exposure of >28.1 mg/m3-years. The estimated risk of death up to age 65 from silicosis after 45 years of exposure at 0.1 mg/m3 silica (the current standard in many countries) was 13 per 1000, while the estimated risk at an exposure of 0.05 mg/m3 was 6 per 1000. Both of these risks are above the risk of 1 per 1000 typically deemed acceptable by the US OSHA. Conclusion: The findings from this pooled analysis add further support to the need to control silica exposure and to lower the occupational standards. Our estimates of lifetime silicosis mortality risk are probably underestimates as, in addition to exposure misclassification, our study might have suffered from outcome misclassification in that silicosis deaths might have been coded to other related causes, such as tuberculosis or chronic obstructive pulmonary disease.

Occupational exposure to vinyl chloride, acrylonitrile and styrene and lung cancer risk (Europe)

Several industry-based cohort studies have addressed the risk of lung cancer following exposure to vinyl chloride, acrylonitrile and styrene, with inconsistent results and usually without smoking adjustment. These exposures are addressed here in a large case–control study with full adjustment for smoking.Almost 6000 subjects were included in a case–control study conducted in seven European countries. For each job they held, local experts assessed the exposure to a number of occupational agents, including vinyl chloride, acrylonitrile and styrene, on the basis of detailed occupational questionnaires. Information on tobacco consumption and other risk factors was also collected.The odds ratio (OR) for ever exposure to vinyl chloride was 1.05 (95% confidence interval, CI: 0.68–1.62) and a modest, non-significant increase in the risk of lung cancer was found in the highest exposed subgroup. The OR for ever exposure to acrylonitrile was 2.20 (95% CI: 1.11–4.36) with a positive dose–response relationship between estimated cumulative exposure and lung cancer risk. No association between exposure to styrene and lung cancer risk was found. In conclusion, we cannot exclude a weak association between occupational exposure to vinyl chloride and lung cancer risk. Exposure to acrylonitrile was associated in our study with risk of lung cancer. Exposure to styrene does not seem to increase lung cancer risk.

Mortality in New Zealand workers exposed to phenoxy herbicides and dioxins.

Aims: To evaluate mortality in New Zealand phenoxy herbicide producers and sprayers exposed to dioxins. Methods: Phenoxy herbicide producers (n = 1025) and sprayers (n = 703) were followed up from 1 January 1969 and 1 January 1973 respectively to 31 December 2000. A total of 813 producers and 699 sprayers were classified as exposed to dioxin and phenoxy herbicides. Standardised mortality ratios (SMR) were calculated using national mortality rates. Results: At the end of follow up, 164 producers and 91 sprayers had died. Cancer mortality was reduced for sprayers (SMR = 0.82, 95% CI 0.57 to 1.14) and increased in exposed production workers (SMR = 1.24, 95% CI 0.90 to 1.67), especially for synthesis workers (SMR = 1.69), formulation and lab workers (SMR = 1.64), and maintenance/waste treatment/cleaning workers (SMR = 1.46). Lymphohaematopoietic cancer mortality was increased in exposed production workers (SMR = 1.65, 95% CI 0.53 to 3.85), especially for multiple myeloma (SMR = 5.51, 95% CI 1.14 to 16.1). Among sprayers, colon cancer (SMR = 1.94, 95% CI 0.84 to 3.83) showed increased mortality. Conclusions: Results showed 24% non-significant excess cancer mortality in phenoxy herbicide producers, with a significant excess for multiple myeloma. Associations were stronger for those exposed to multiple agents including dioxin during production. Overall cancer mortality was not increased for producers and sprayers mainly handling final technical products, although they were likely to have been exposed to TCDD levels far higher than those currently in the general New Zealand population.

Gender differences in occupational exposure patterns

Objectives The authors conducted a population-based survey to examine gender differences in occupational exposure patterns and to investigate whether any observed differences are due to: (a) gender differences in occupational distribution; and/or (b) gender differences in tasks within occupations. Methods Men and women aged 20–64 years were randomly selected from the Electoral Roll and invited to take part in a telephone interview, which collected information on self-reported occupational exposure to specific dusts and chemicals, physical exposures and organisational factors. The authors used logistic regression to calculate prevalence ORs and 95% CIs comparing the exposure prevalence of males (n=1431) and females (n=1572), adjusting for age. To investigate whether men and women in the same occupation were equally exposed, the authors also matched males to females on current occupation using the five-digit code (n=1208) and conducted conditional logistic regression adjusting for age. Results Overall, male workers were two to four times more likely to report exposure to dust and chemical substances, loud noise, irregular hours, night shifts and vibrating tools. Women were 30% more likely to report repetitive tasks and working at high speed, and more likely to report exposure to disinfectants, hair dyes and textile dust. When men were compared with women with the same occupation, gender differences were attenuated. However, males remained significantly more likely to report exposure to welding fumes, herbicides, wood dust, solvents, tools that vibrate, irregular hours and night-shift work. Women remained more likely to report repetitive tasks and working at high speed, and in addition were more likely to report awkward or tiring positions compared with men with the same occupation. Conclusion This population-based study showed substantial differences in occupational exposure patterns between men and women, even within the same occupation. Thus, the influence of gender should not be overlooked in occupational health research.