CNS tumors and exposure to acrylonitrile: inconsistency between experimental and epidemiology studies.
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Acrylonitrile is a potent CNS tumorigen in rats leading to concern that it may be a tumorigen in humans. There have been 12 epidemiology studies of 37,352 workers exposed to acrylonitrile which evaluate CNS cancers. We summarize and evaluate these epidemiology studies for CNS cancers using the methods of meta-analysis. Our analyses indicate that workers with acrylonitrile exposure have null findings for CNS cancer (relative risk = 1.1, 95% confidence interval 0.8-1.5), which are in stark contrast to the projected risk to humans using the rat findings (relative risk = 3.5, 95% confidence interval 3.0-4.0). We discuss several explanations for the inconsistency between animal and human findings, including the possibility that the acrylonitrile-induced rat CNS tumors may not be relevant to humans. Given the rarity of CNS tumors in humans and a lack of understanding of the causal mechanisms of these tumors in rats, however, a more definitive conclusion will have to await additional experimental and observational data. Nevertheless, the epidemiology evidence indicates that acrylonitrile is not a potent CNS tumorigen. (+info)
Dioxin and diabetes mellitus: an analysis of the combined NIOSH and Ranch Hand data.
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OBJECTIVES: To reanalyze in a similar manner the two principal studies of TCDD (tetrachlorodibenzo-p-dioxin) and diabetes in an attempt to reconcile disparate results. METHODS: Data from 990 United States Air Force veterans (Ranch Hand) and 1275 referents were reanalyzed, and a NIOSH population of 267 chemical workers and 227 referents. The Ranch Hand veterans had lower concentrations of lipid adjusted serum TCDD (median 12 parts per trillion (ppt)) than the NIOSH workers (median 75 ppt) when examined in the late 1980s. An analysis was conducted of the combined data sets, adopting a uniform approach to outcome definition, data analysis, and covariate control. RESULTS: The combined exposed groups did not differ markedly from the combined non-exposed groups for prevalence of diabetes (odds ratio (OR) 1.17, 95% confidence interval (95% CI) 0.92 to 1.48), with no evidence of heterogeneity of exposure effect between studies. Also virtually no difference was found between combined exposed and non-exposed groups in mean fasting serum glucose (difference in log serum glucose 0.002, 95% CI -0.006 to 0.010), and there was little evidence in either study of a dose-response trend for fasting serum glucose. An increasing trend was found (p=0.0001) in prevalence of diabetes with increased TCDD (at the time of examination or at time of last exposure) among the Ranch Hand population, with excess risk largely confined to the highest 8% of the exposed group (>78 ppt serum TCDD), which had an OR of 3.21 (95% CI 1.81 to 5.72) versus those with <10 ppt TCDD. However, no such positive dose-response was found in the NIOSH population. CONCLUSIONS: There was little overall evidence that the exposed workers were at higher risk than the non-exposed workers of diabetes or abnormal fasting glucose. However, the Ranch Hand subjects showed a positive dose-response for diabetes, whereas the more highly exposed NIOSH subjects did not. The reason for the difference in diabetes dose-response trends between the two studies is unknown. (+info)
The interaction between copper and coronary risk indicators.
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We studied the effects of external copper exposure on plasma copper, serum lipids, lipoproteins and apolipoproteins in workers who have excessive contact with copper. Fifty-eight healthy Turkish males who were working in the copper processing industry and 33 control subjects were examined. Copper concentration was measured by flame atomic absorption spectrometry, lipid and lipoprotein levels were detected by spectrophotometry and apolipoproteins were measured with a nephelometer. There was no significant difference in plasma copper between the workers and the controls. However, in the worker group, the mean levels of TC, LDL-C, apoAI, apoB and Lp (a) were significantly higher while the mean level of HDL-C was significantly lower than that of the controls. In addition, there was a significant positive correlation between plasma copper and LDL-C only in the workers group. Our findings suggest that excessive contact with copper may contribute to coronary risk factors. (+info)
Estimating the extent of the health hazard posed by high-production volume chemicals.
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We used structure-activity relationship modeling to estimate the number of toxic chemicals among the high-production volume (HPV) group. We selected 200 chemicals from among the HPV chemical list and predicted the potential of each for its ability to induce a variety of adverse effects including genotoxicity, carcinogenicity, developmental, and systemic toxicity. We found a significantly less than expected proportion of toxic chemicals among the HPV sample when compared to a reference set of 10,000 chemicals representative of the universe of chemicals. (+info)
Dioxin exposure in a residential community.
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The Agency for Toxic Substances and Disease Registry (ATSDR) conducted biological testing to assess dioxin exposure in residents of a community who lived in an area with heavy chemical industry. Dioxin concentrations were measured in blood serum samples from 28 adult residents of the community. Fourteen of those tested had blood dioxin concentrations that exceeded the 95th percentile prediction level of an age-matched comparison population. Specific congener analyses indicated that the elevated dioxin concentrations were primarily due to high concentrations of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), 1,2,3,7,8 pentachlorodibenzo-p-dioxin (PeCDD), and hexachlorodibenzo-p-dioxins (HxCDs). Principal components analysis (PCA) indicated that the profiles of dioxin congeners were different in people with elevated blood dioxin concentrations compared to those with background concentrations. Elevated blood dioxin concentrations were detected only in older members of the population, which suggests that dioxin exposures were higher in the past. The sources of the dioxin exposure have not been identified. (+info)
Exposure to hexahydrophthalic and methylhexahydrophthalic anhydrides--dose-response for sensitization and airway effects.
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OBJECTIVES: This study clarified the exposure-response relationships for the organic acid anhydrides (OAA) hexahydrophthalic (HHPA) and methylhexahydrophthalic (MHHPA) anhydrides and the development of specific immunoglobulin (IG) E and G antibodies and work-related symptoms. METHODS: In an epoxy resin-using factory, air levels of OAA were determined by gas chromatography-mass spectrometry. Occupational, smoking, and medical histories (questionnaire) were obtained for 154 exposed workers and 57 referents. Work-related symptoms of the eyes and airways were recorded, and OAA metabolites were analyzed in urine. A skin-prick test with common allergens and conjugates of OAA were performed. Specific IgE (radioallergosorbent test) and IgG (enzyme-linked immumosorbent assay) antibodies were determined in serum, and spirometry was performed. RESULTS: Air levels of the OAA were low (HHPA < 1 to 94, MHHPA < 3 to 77 microg/m3) and associated with the concentrations of the OAA metabolites in urine. Furthermore, for the exposed workers, there were high prevalences of sensitization (IgE 22%, IgG 21%), which correlated with the exposure. Neither atopy nor smoking increased this risk significantly. Furthermore, work-related symptoms were more prevalent among the exposed workers than among the referents (eyes 23% versus 14%, nose 28% versus 16%, nose bleeding 8% versus 0%, lower airways 10% versus 4%), and they were related to the exposure (adjusted prevalence odds ratios (POR) in the highest group 7.7, 3.6 and 17, respectively) and the IgE levels (POR 4.9, 3.1 and 5.6, respectively). CONCLUSIONS: In spite of the very low OAA levels in the air and metabolites in the urine, there were high and exposure-related risks of specific IgE and IgG sensitization and of work-related symptoms for the eyes, nose (especially bleeding), and lower airways. (+info)
Hearing loss among workers exposed to moderate concentrations of solvents.
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OBJECTIVES: It is known that some industrial organic solvents are ototoxic. This study was aimed at evaluating the hearing effects of a mixture of organic solvents alone or in combination with noise on employees in paint and lacquer enterprises. The concentration of solvents was below the occupational exposure limits (OEL) for most of the subjects. METHODS: Altogether 517 subjects were divided into the following three groups: persons with no risk due to noise or organic solvent exposure at the workplace, workers exposed to organic solvents only, and workers exposed to both organic solvents and noise. RESULTS: The relative risk (RR) of hearing loss in the solvent-only exposure group was significantly increased (RR 4.4 and RR 2.8 for noise exposure of < 80 dB-A and < 85 dB-A, respectively) in a wide range of frequencies (2-8 kHz). No additional risk in the solvent + noise exposure group was found (RR 2.8). Hearing thresholds were significantly poorer in a wide range of frequencies (1-8 kHz) for both groups exposed to solvents, when compared with the reference group. The mean hearing thresholds at frequencies of 2-4 kHz were poorer for workers exposed to solvents + noise than for the solvent-only group; this finding suggests an additional effect for noise. However, there was no correlation between hearing loss and the extent of solvent exposure. CONCLUSIONS: The results indicate that occupational organic solvent exposure at moderate concentrations increases the risk of hearing loss, and the ototoxic effects should be considered when the health effects of exposed workers are monitored. (+info)
Heterogeneity in sources of exposure variability among groups of workers exposed to inorganic mercury.
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Many exposure assessment strategies rely on the occupational group as the unit of analysis in which workers are classified on the basis of job title, location, or on other characteristics related to the workplace or the job. Although statistical methods that combine exposure data collected on workers from different occupational groups are more efficient, the underlying assumption that the degree of variation over time and among workers is the same for all groups has yet to be fully investigated. Given the utility of different modeling approaches when assessing exposures, we investigated assumptions of homogeneity of variance within and between workers using both random- and mixed-effects models. In our study of four groups of workers exposed to inorganic mercury (Hg) at a chloralkali plant, there was no evidence of significant heterogeneity in the levels of variation over time or between workers for air Hg levels. For the biological monitoring data, however, our findings indicate that groups did not share common levels of variability and that it was not appropriate to pool the data and obtain single estimates of the within- and between-worker variance components. Classification of job group as a random or fixed effect had no effect on the results and yielded the same conclusions when the models were compared. To illustrate effects related to the proper specification of a model, the likelihood of exceeding certain levels (which is a function of the parameters of the underlying distribution of the natural log-transformed exposures) was evaluated using the results obtained from the different models. Although the probability that workers' mean exposures exceeded occupational exposure limits for air, urine and blood Hg was generally low (<10%) for all groups except maintenance workers, the estimated values sometimes varied depending upon the particular model that was applied. Given the growing use of random- and mixed-effects models that combine data across occupational groups, additional studies are warranted to evaluate whether it is reasonable to assume common variances and covariances among measurements collected on workers from different groups. (+info)