Trichloroethylene and cancer in humans: recognizing the need for an evidence based analysis.
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Carcinogens↗
Biomedical subjects
David H Garabrant
Publications and source records attributed to David H Garabrant.
The association of body mass index and pancreatic cancer in residents of southeastern Michigan, 1996-1999.
Increased body mass index has emerged as a potential risk factor for pancreatic cancer. The authors examined whether the association between body mass index and pancreatic cancer was modified by gender, smoking, and diabetes in residents of southeastern Michigan, 1996-1999. A total of 231 patients with newly diagnosed adenocarcinoma of the exocrine pancreas were compared with 388 general population controls. In-person interviews were conducted to ascertain information on demographic and lifestyle factors. Unconditional logistic regression models estimated the association between body mass index and pancreatic cancer. Males' risk for pancreatic cancer significantly increased with increasing body mass index (p(trend) = 0.048), while no relation was found for women (p(trend) = 0.37). Among nonsmokers, those in the highest category of body mass index were 3.3 times (95% confidence interval: 1.2, 9.2) more likely to have pancreatic cancer compared with those with low body mass index. In contrast, no relation was found for smokers (p(trend) = 0.94). While body mass index was not associated with pancreatic cancer risk among insulin users (p(trend) = 0.11), a significant increase in risk was seen in non-insulin users (p(trend) = 0.039). This well-designed, population-based study offered further evidence that increased body mass index is related to pancreatic cancer risk, especially for men and nonsmokers. In addition, body mass index may play a role in the etiology of pancreatic cancer even in the absence of diabetes.
Adult↗
Amalgam exposure and neurological function.
Concerns regarding the safety of silver-mercury amalgam fillings continue to be raised in the absence of any direct evidence of harm. The widespread population exposure to amalgam mandated that a thorough investigation be conducted of its potential effects on the nervous system. The National Institute of Dental and Craniofacial Research and U.S. Air Force investigators collaborated in the ongoing Air Force Health Study (AFHS) of Vietnam era veterans. The primary study question involved adverse health effects associated with exposure to herbicides or dioxin. An assessment of exposure to dental amalgam fillings was added to the 1997-1998 health examination to investigate possible associations between amalgam exposure and neurological abnormalities. Our study population consisted of 1663 dentate AFHS participants, comprised of 986 AFHS controls and 677 Ranch Hand veterans who were exposed to dioxin in Vietnam. Two hundred and fifty-two of the participants had confirmed diabetes mellitus. Study outcomes included clinical neurological signs, vibrotactile thresholds, and summary variables for different levels of peripheral neuropathy. A limitation of our study is that our database did not include more sensitive continuous measures such as nerve conduction studies. No significant associations were found between amalgam exposure and clinical neurological signs of abnormal tremor, coordination, station or gait, strength, sensation, or muscle stretch reflexes or for any level of peripheral neuropathy among our study participants. A statistically significant association was detected between amalgam exposure and the continuous vibrotactile sensation response for the combined non-diabetic participants and separately for non-diabetic AFHS controls. No significant association in this measure was detectable for non-diabetic Ranch Hand veterans or among the combined diabetic participants. The association is a sub-clinical finding that was not associated with symptoms, clinically evident signs of neuropathy, or any functional impairment. Overall, we found no association between amalgam exposure and neurological signs or clinically evident peripheral neuropathy. Our findings do not support the hypothesis that exposure to amalgam produces adverse, clinically evident neurological effects.
Dental Amalgam↗
Mesothelioma and lung cancer among motor vehicle mechanics: a meta-analysis.
We conducted a systematic review and analysis of the epidemiological literature that examines the risk of lung cancer and mesothelioma among motor vehicle mechanics who may have been engaged in brake repair and, thus, were potentially exposed to asbestos. All relevant studies were classified into three tiers according to their quality. Tier III (lowest quality) studies were cited for completeness, but were not included in the meta-analysis. Meta relative risks (meta-RRs) were calculated for mesothelioma and lung cancer using both fixed and random effects models for Tiers I and II, separately, followed by stratified analyses based on study design or exposure characterization (garage workers versus brake workers) and, for lung cancer studies, based on adequate adjustment for smoking. The meta-analysis for Tier I (higher quality) and Tier II (lower quality) studies of mesothelioma yielded RR estimates of 0.92 (95% CI 0.55-1.56) and 0.81 (95% CI 0.52-1.28), respectively. Further stratification according to exposure characterization did not affect the results. The meta-analysis for lung cancer produced RR estimates of 1.07 (95% CI 0.88-1.31) for Tier I and 1.17 (95% CI 1.01-1.36) for Tier II. When the lung cancer analysis was limited to studies that used adequate control for smoking, the resulting RR estimate was 1.09 (95% CI 0.92-1.28). Based on these findings, we conclude that employment as a motor vehicle mechanic does not increase the risk of developing mesothelioma. Although some studies showed a small increase in risk of lung cancer among motor vehicle mechanics, the data on balance do not support a conclusion that lung cancer risk in this occupational group is related to asbestos exposure.
Asbestos↗
Absence of sensory neuropathy among workers with occupational exposure to chlorpyrifos.
Several studies have reported the occurrence of sensory neuropathy with exposure to chlorpyrifos and other organophosphorus insecticides, at levels not associated with overt toxicity. We evaluated 113 chemical workers, including 53 of 66 (80%) eligible chlorpyrifos workers and 60 of 74 (81%) randomly selected referent workers, to identify evidence of sensory neuropathy or subclinical neuropathy. Compared to referents, chlorpyrifos subjects had significantly longer duration of work in chlorpyrifos-exposed areas (9.72 vs. 0.01 years; P < 0.0001), greater cumulative chlorpyrifos exposure (64.16 vs. 0.69 mg/m(3). day; P < 0.0001), higher urine 3,5,6-trichloro-2-pyridinol (TCP) excretion (108.6 vs. 4.3 microg/g creatinine; P < 0.0001), and lower plasma butyrylcholinesterase (BuChE) activity (7281 vs. 8176 mU/ml; P = 0.003). Despite exposures among chlorpyrifos subjects to levels at which well-described physiological effects on B-esterases exist, the frequency of symptoms or signs of neuropathy did not differ significantly between groups, and the only 2 subjects fulfilling criteria for confirmed neuropathy were both in the referent group. Mean nerve conduction study results were comparable to established control values and did not differ significantly between groups. We found no evidence of sensory neuropathy or isolated peripheral abnormalities among subjects with long-term chlorpyrifos exposure at levels known to be associated with the manufacturing process.
Adolescent↗
Respiratory impairment due to asbestos exposure in brake-lining workers.
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Asbestos↗
Cancer in US Air Force veterans of the Vietnam War.
Cancer incidence and mortality were summarized in Air Force veterans of the Vietnam War. The index subjects were Operation Ranch Hand veterans who sprayed 2,3,7,8 tetrachlorodibenzo-p-dioxin (dioxin)-contaminated herbicides in Vietnam. Comparisons served in Southeast Asia during the same period but did not spray herbicides. We assessed cancer incidence and mortality using national rates and contrasted cancer risk in each of three Ranch Hand dioxin exposure categories relative to comparisons. The incidence of melanoma and prostate cancer was increased among white Ranch Hand veterans relative to national rates. Among veterans who spent at most 2 years in Southeast Asia, the risk of cancer at any site, of prostate cancer and of melanoma was increased in the highest dioxin exposure category. These results appear consistent with an association between cancer and dioxin exposure.
Adult↗
The effects of occupational exposure to chlorpyrifos on the neurologic examination of central nervous system function: a prospective cohort study.
Questions persist about adverse effects such as impaired cognition and attention, incoordination, spasticity, or parkinsonism from chronic, low-level exposures to organophosphate (OP) compounds. In a prospective cohort study, we evaluated chlorpyrifos-manufacturing workers and a referent group on 2 occasions, 1 year apart, to determine whether occupational exposure to chlorpyrifos produced clinically evident central nervous system (CNS) dysfunction. Chlorpyrifos subjects had significantly higher TCP excretion and lower average BuChE activity than referents in a range in which physiological effects on B-esterases exist. Few subjects had neurologic symptoms or signs, and there were no significant group differences in terms of signs at baseline or second examinations. Chronic chlorpyrifos exposure produced no clinical evidence of cortical, pyramidal tract, extrapyramidal, or other CNS dysfunction among chlorpyrifos subjects compared with referents, either at baseline or after 1 year of additional chlorpyrifos exposure.
Adult↗
Scleroderma and solvent exposure among women.
Exposure to solvents has been reported to increase the risk of scleroderma. The authors investigated the relation between exposures to solvents in occupational and hobby settings and the development of scleroderma among women in a case-control study with population-based controls in Michigan (1980-1991) and Ohio (1980-1992). A total of 660 cases and 2,227 frequency-matched controls were interviewed by telephone. Diagnoses of scleroderma were verified by medical records review. Paint thinners and removers were significantly associated with scleroderma both by self-report (odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.4, 2.6) and after expert review (OR = 2.0, 95% CI: 1.5, 2.6). Other petroleum distillates (gasoline and mineral spirits) were not significantly associated with scleroderma after controlling for other correlated exposures in multivariable analyses. Trichloroethylene was associated with scleroderma both by self-report (OR = 2.0, 95% CI: 0.8, 4.8) and after expert review (OR = 1.9, 95% CI: 0.6, 6.6), but not significantly. Analyses by duration of exposure found that risk increased with the duration of use of any of the solvents (OR = 1.01/year of exposure, 95% CI: 1.01, 1.02), but there was no evidence of increasing risk with increasing duration of exposure for any specific solvent studied. In summary, exposures to paint thinners and removers were associated with scleroderma in women but showed no evidence of increasing risk with increasing duration. Exposures to other specific chlorinated and nonchlorinated hydrocarbon solvents were not clearly associated with scleroderma.
Case-Control Studies↗
Epidemiology of latex sensitization and allergies in health care workers.
Although it is often claimed that health care workers are at increased risk of latex sensitization and type I allergies, there has been no systematic analysis of the epidemiologic studies that are relevant to this conclusion. A systematic analysis of the epidemiologic literature found that, in the past 14 years, there have been 48 epidemiologic studies of type I latex allergy among health care workers. Of these, 2 cohort studies estimated the incidence of latex sensitization by skin prick testing at between 1% and 2.5% per year. Neither compared the risk to that in the general population. The prevalence of sensitization in health care workers varied between 0% and 30%, yet this large variation was unexplained. Increased risk of sensitization was not clearly associated with the duration of work in health care, the time spent wearing latex gloves, the frequency of exposure, the specific job categories, the use of powdered versus nonpowdered latex gloves, the use of latex versus nonlatex gloves, or any measurements of ambient exposure to latex proteins. The epidemiologic studies do not support a conclusion that health care workers are at clearly increased risk of latex sensitization or type I allergies compared to other occupations in the United States. The role of latex gloves in causing latex sensitization and type I allergic symptoms remains poorly defined because of the inconsistent results across studies. Future epidemiologic studies are needed that include measured exposures to latex antigens, that compare health care workers to appropriate referent groups, and that address confounding by atopy, age, sex, and race.
Gloves, Protective↗
Review of 2,4-dichlorophenoxyacetic acid (2,4-D) epidemiology and toxicology.
The scientific evidence in humans and animals relevant to cancer risks, neurologic disease, reproductive risks, and immunotoxicity of 2,4-D was reviewed. Despite several thorough in vitro and in vivo animal studies, no experimental evidence exists supporting the theory that 2,4-D or any of its salts and esters damages DNA under physiologic conditions. Studies in rodents demonstrate a lack of oncogenic or carcinogenic effects following a lifetime dietary administration of 2,4-D. Epidemiologic studies provide scant evidence that exposure to 2,4-D is associated with soft tissue sarcoma, non-Hodgkin's lymphoma, Hodgkin's disease, or any other cancer. Overall, the available evidence from epidemiologic studies is not adequate to conclude that any form of cancer is causally associated with 2,4-D exposure. There is no human evidence of adverse reproductive outcomes related to 2,4-D. The available data from animal studies of acute, subchronic, and chronic exposure to 2,4-D, its salts, and esters show an unequivocal lack of systemic toxicity at doses that do not exceed renal clearance mechanisms. There is no evidence that 2,4-D in any of its forms activates or transforms the immune system in animals at any dose. At high doses, 2,4-D damages the liver and kidney and irritates mucous membranes. Although myotonia and alterations in gait and behavioral indices are observed after overwhelming doses of 2,4-D, alterations in the neurologic system of experimental animals are not observed with the administration of doses in the microgram/kg/day range. It is unlikely that 2,4-D has any neurotoxic potential at doses below those required to induce systemic toxicity.
2,4-Dichlorophenoxyacetic Acid↗