A systematic review of myeloid leukemias and occupational pesticide exposure.

OBJECTIVE: To conduct a systematic review and meta-analyses of published studies examining the association between myeloid leukemias (ML) and occupational pesticide exposure. METHODS: Studies were identified from a MEDLINE search through 31 May 2006 and from the reference lists of identified publications. Studies were summarized and evaluated for publication bias. Relative risk estimates for ML were extracted from 17 cohort and 16 case-control studies published between 1979 and 2005. Fixed- or random-effect meta-analysis models were used depending on the presence of heterogeneity between studies. Separate analyses were conducted after stratification for study design, occupational group, ML subtype or gender. RESULTS: The overall meta-rate ratio estimate (meta-RR) for the cohort studies was 1.21 (95% confidence interval [CI] 0.99-1.48). Substantial heterogeneity existed among cohort studies (p=1.064 x 10(-5)), mainly reflecting the varying occupational categories examined. The meta-RR was 6.32 (95% CI: 1.90-21.01) for manufacturing workers and 2.14 (95% CI: 1.39-3.31) for pesticide applicators. After stratification of cohort studies by specific ML subtype, an increased risk of acute myeloid leukemia (AML) was found (meta-RR: 1.55; 95% CI: 1.02-2.34). No significant heterogeneity was detected among case-control studies and an increased risk of chronic myeloid leukemia (CML) was found among men (meta-RR: 1.39; 95% CI: 1.03-1.88) and farmers or agricultural workers (meta-RR: 1.38; 95% CI: 1.06-1.79). CONCLUSION: The strongest evidence of an increased risk of ML comes from manufacturing workers and pesticide applicators. Further studies will be needed to correlate reliable exposure data within these specific occupational groups with well-defined subtypes of leukemia to refine this assessment

Carcinogenic potential of formaldehyde in occupational settings: a critical assessment and possible impact on occupational exposure levels.

OBJECTIVES: To review epidemiological studies which led to a change in the classification of formaldehyde by the International Agency for Research on Cancer (IARC) in 2004 as well as studies published thereafter, with the objective to examine whether occupational exposure levels for formaldehyde should be adapted. METHOD: Cohort and case-control studies investigating the association between occupational exposure to formaldehyde and nasopharyngeal cancer (NPC) and reporting estimates of formaldehyde exposure as well as the most recent meta-analyses, published after 1994, were reviewed. RESULTS: Evidence of an association between occupational formaldehyde exposure and NPC appears debatable. Results of the cohort studied by Hauptmann et al. (Am J Epidemiol 159(12):1117-1130, 2004) were key findings in the IARC evaluation. In this study, mortality from NPC was elevated compared with that of the US general population. However, internal comparison analysis using alternative categorization revealed that none of the relative risk for NPC was statistically significantly increased in any category of exposure (Marsh and Youk in Regul Toxicol Pharmacol 42(3):275-283, 2005) and re-analyses of the data highlighted the inappropriateness of the exposure assessment used by Hauptmann et al. (Am J Epidemiol 159(12):1117-1130, 2004) and Marsh et al. (Regul Toxicol Pharmacol 47(1):59-67, 2007). Two other cohorts (Coggon et al. in J Natl Cancer Inst 95(21):1608-1615, 2003; Pinkerton et al. in Occup Environ Med 61(3)193-200, 2004) reported no increase in NPC. Two case-control studies brought some evidence of an increased risk of NPC but the assessment of exposure levels was uncertain. DISCUSSION: Human studies fail to raise a convincing conclusion concerning the carcinogenicity of formaldehyde and are not helpful to delineate a possible dose-response relationship. Experimental data indicate that in rats, the carcinogenic activity of formaldehyde is associated with cytotoxic/proliferative mechanisms. Therefore protecting from these effects associated with formaldehyde exposure should be sufficient to protect from its potential carcinogenic effects, if any in humans. CONCLUSION: Current occupational exposure levels to formaldehyde, set to protect against local irritation, should not be adapted

Risk of leukaemia among pesticide manufacturing workers: a review and meta-analysis of cohort studies.

PURPOSE: The purpose of this paper is to review available cohort studies and to estimate quantitatively the association between occupational exposure in plants manufacturing pesticides and leukaemia. METHODS: Following a systematic literature search, relative risks were extracted from 14 studies published between 1984 and 2004. Fixed effect analyses were carried out as heterogeneity between studies was not detected. Meta-analyses were performed on the whole set of data and separate analyses were conducted for specific chemical classes of pesticides as well as type of leukaemia. RESULTS: The meta-rate ratio estimate for all studies was 1.43 (95% confidence interval [CI] 1.05-1.94). After stratification by chemical class, consistent increases in the risk of leukaemia were found in all groups but statistical significance was found only for phenoxy herbicides unlikely to have been contaminated with dioxins and furans. This last finding appears equivocal in view of the existing literature. The separate analysis conducted on leukaemias from the myeloid lineage showed the highest relative risk (6.99; 95% CI 1.96-24.90). There was no obvious indication of publication bias. CONCLUSION: The overall meta-analysis among pesticide manufacturing workers provides quantitative evidence to consider occupational exposure to pesticides as a possible risk factor for leukaemia but available data are too scarce for causality ascertainment. Epidemiological evidence did not allow identifying a specific pesticide or chemical class that would be responsible for the increased risk. Exposure to pesticides may be a significant risk factor for specifically developing myeloid leukaemia and there is a need for additional large well-conducted studies with clear definition of exposure and of leukaemia type(s)