Garabrant & 2,4D
"There is no human evidence of adverse reproductive outcomes related to 2,4-D...There is no evidence that 2,4-D in any of its forms activates or transforms the immune system in animals at any dose...It is unlikely that 2,4-D has any neurotoxic potential at doses below those required to induce systemic toxicity."

Garabrant & Latex Allergy
"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."

Garabrant & Dioxin in Vets
"...we consistently found a statistically significant increased risk of all indices of peripheral neuropathy among Ranch Hand veterans in the high exposure category in 1997, and a statistically significant increased risk of diagnosed peripheral neuropathy, incorporating bilateral vibrotactile abnormalities of the great toes, in the high category in 1992."

Garabrant & Organic Solvents
"Existing studies, on aggregate, do not show conclusively that solvents (either as a group of chemicals or individual chemicals) are causally associated with any connective tissue disease."

"We found no objective neurologic evidence supportive of toxic encephalopathy or any other uniform syndrome among these individuals, and most complaints were explained by neuropsychological factors or conditions unrelated to occupational solvent exposure."

Garabrant & Wood Dust
"This study provides additional evidence that heavy exposure to wood dusts may be associated with reduced risk of colon cancer in males after adjustment for other known causes of colon cancer."

Garabrant & Organochlorine Pesticides
"Increased odds ratios were observed for self-reported exposures to chloropropylate and DDT, as well as for the summary group of organochlorine pesticides which included all of these materials, though these associations were not significant."

Garabrant & Silicon Breast Implants
"...we found no increased risk of SSc [systemic sclerosis] among women with silicone breast implants, equivocal evidence of risk from other silicone exposures, and no evidence of risk from silica exposure."

Garabrant & Nicotine Patches
"We conclude that transdermal nicotine patches are of limited efficacy in achieving long-term smoking cessation and that the relative costs and benefits of this treatment are not adequately specified."

Garabrant & Asbestos
"This study suggests not only that occupational exposure to asbestos is not a risk factor for colon cancer in the general population of Los Angeles, but also that observed associations between asbestos and colon cancer should not be interpreted as causal unless confounding by nonoccupational factors has been evaluated and controlled."

Garabrant & Occupational Cancer
"Investigation of cancer clusters often presents a difficult scientific challenge, which requires careful case ascertainment, calculations of risk based on an appropriate reference population, identification of distant past exposures, and a search for common elements among the cases."
 
 
 

Garabrant & 2,4D

"There is no human evidence of adverse reproductive outcomes related to 2,4-D...There is no evidence that 2,4-D in any of its forms activates or transforms the immune system in animals at any dose...It is unlikely that 2,4-D has any neurotoxic potential at doses below those required to induce systemic toxicity."

Crit Rev Toxicol. 2002 Jul;32(4):233-57.
Review of 2,4-dichlorophenoxyacetic acid (2,4-D) epidemiology and toxicology.

Garabrant DH, Philbert MA.
Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor 48109-2029, USA. dhg@umich.edu

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.
 

Garabrant & Latex Allergy

"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."

J Allergy Clin Immunol. 2002 Aug;110(2 Suppl):S82-95.  R
Epidemiology of latex sensitization and allergies in health care workers.

Garabrant DH, Schweitzer S.
Occupational Medicine, University of Michigan School of Public Health and University of Michigan School of Medicine, and the Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48104, USA. dhg@umich.edu

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.
 

Garabrant & Dioxin in Vets

"...we consistently found a statistically significant increased risk of all indices of peripheral neuropathy among Ranch Hand veterans in the high exposure category in 1997, and a statistically significant increased risk of diagnosed peripheral neuropathy, incorporating bilateral vibrotactile abnormalities of the great toes, in the high category in 1992."
 

Neurotoxicology. 2001 Aug;22(4):479-90.  
Serum dioxin and peripheral neuropathy in veterans of Operation Ranch Hand.

Michalek JE, Akhtar FZ, Arezzo JC, Garabrant DH, Albers JW.
Air Force Research Laboratory, Brooks Air Force Base, TX, USA. joel.michalek@brooks.af.mil

We studied whether exposure to Agent Orange and its contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), during the Vietnam War is related to peripheral neuropathy. The index subjects were veterans of Operation Ranch Hand, the unit responsible for aerial herbicide spraying in Vietnam from 1962 to 1971. We report peripheral nerve function assessed in 1982, 1985, 1987, 1992 and 1997, nerve conduction velocities measured in 1982, and vibrotactile thresholds of the great toes measured in 1992 and 1997. We assigned each Ranch Hand veteran to one of three exposure categories named "background", "low" and "high", based on his serum dioxin level. Other than the bilateral vibrotactile abnormalities, we consistently found a statistically significant increased risk of all indices of peripheral neuropathy among Ranch Hand veterans in the high exposure category in 1997, and a statistically significant increased risk of diagnosed peripheral neuropathy, incorporating bilateral vibrotactile abnormalities of the great toes, in the high category in 1992. Restricting to the enlisted veterans did not alter these results. Cautious interpretation of these results is appropriate until the relationship between pre-clinical diabetes mellitus and peripheral neuropathy is further evaluated in future examinations.
 

Garabrant & Organic Solvents

"Existing studies, on aggregate, do not show conclusively that solvents (either as a group of chemicals or individual chemicals) are causally associated with any connective tissue disease."
 

Arthritis Res. 2000;2(1):5-15. Epub 1999 Dec 01.
Epidemiology of organic solvents and connective tissue disease.

Garabrant DH, Dumas C.

Department of Environmental Health Sciences, University of Michigan, School of Public Health, Ann Arbor, Michigan 48109-2029, USA. dhg@umich.edu

Case reports suggest that solvents are associated with various connective tissue diseases (systemic sclerosis, scleroderma, undifferentiated connective tissue disease, systemic lupus erythematosis, and rheumatoid arthritis), particularly systemic sclerosis. A small number of epidemiological studies have shown statistically significant but weak associations between solvent exposure, systemic sclerosis, and undifferentiated connective tissue disease. However, the interpretation of these positive findings is tempered by a lack of replication, an inability to specify which solvents convey risk, and an absence of increasing risk with increasing exposure. Existing studies, on aggregate, do not show conclusively that solvents (either as a group of chemicals or individual chemicals) are causally associated with any connective tissue disease. Further investigations should be carried out to replicate the positive existing findings and to specify the solvents and circumstances of exposure that carry risk.
 

"We found no objective neurologic evidence supportive of toxic encephalopathy or any other uniform syndrome among these individuals, and most complaints were explained by neuropsychological factors or conditions unrelated to occupational solvent exposure."

J Occup Environ Med. 2000 Apr;42(4):410-23.  Related Articles, Links
Neurologic evaluation of workers previously diagnosed with solvent-induced toxic encephalopathy.

Albers JW, Wald JJ, Garabrant DH, Trask CL, Berent S.
Department of Neurology, University of Michigan Health System, Ann Arbor, USA.

We examined 52 railroad workers with long-term occupational solvent exposures (average 22 years duration) who had been previously diagnosed by others as having solvent-induced toxic encephalopathy. All described episodes of transient intoxication associated with occupational solvent exposure. Persistent symptoms developed, an average, 16 years after exposure onset and included impaired memory (38), altered mood (21), imbalance (18), and headache (17). Thirteen workers had mild mental status abnormalities, but none fulfilled conventional clinical criteria for encephalopathy or dementia. None had abnormal blink reflex (51) or abnormal electroencephalographic (39) studies. Eight of 47 magnetic resonance imaging studies showed evidence of scattered ischemic lesions among workers with known diabetes mellitus (2), elevated blood pressure (4), or peripheral vascular disease (2). One magnetic resonance imaging scan showed mild cortical atrophy. In stepwise multiple linear and logistic regression models, no statistically significant (P < 0.05) dose-response relationships were found between exposure duration and symptoms or signs that were suggestive of encephalopathy. However, the number of symptoms (P < 0.001) and the number of signs (P = 0.05) were associated with current use of central nervous system-active medications. Further, lower Mini-Mental Status Examination scores were associated with a history of alcohol abuse (P = 0.01) and lower educational level (P = 0.03). The number of chief symptoms involving memory, mood, balance, or headache differed significantly among workers in different geographic sites (F(3.48) = 2.94, P = 0.04), a finding that was not explained by job title or exposure duration. There also was a significant (P = 0.0001) inverse relationship between initial exposure year (r2 = 0.60) or total years of exposure through 1987 (r2 = 0.56) and interval to major neurologic symptom onset, suggesting that factors other than solvent exposure account in part for worker complaints. We found no objective neurologic evidence supportive of toxic encephalopathy or any other uniform syndrome among these individuals, and most complaints were explained by neuropsychological factors or conditions unrelated to occupational solvent exposure.
 

Garabrant & Wood Dust

"This study provides additional evidence that heavy exposure to wood dusts may be associated with reduced risk of colon cancer in males after adjustment for other known causes of colon cancer."

Int J Occup Environ Health. 1998 Jul-Sep;4(3):179-83.
Wood-dust exposures and cancer of the colon.

Simpson CL, Garabrant DH, Fryzek J, Homa DM, Peters RK.
Division of Occupational and Environmental Medicine, Wayne State University, UHC 4J, 4201 St. Antoine, Detroit, MI 48201, USA.

Previous studies of workers exposed to wood dusts have shown a decreased risk of cancer of the colon in these workers. However, none of these studies adequately controlled for potential confounders, such as physical activity, diet, and family history of colorectal cancer. The purpose of this case-control study was to evaluate the association between exposure to wood dust and risk for colon cancer after adjusting for potential confounders. Four hundred nineteen male cases of adenocarcinoma of the colon, identified from the Los Angeles County Cancer Surveillance Program, were individually matched to neighborhood controls based on gender and date of birth. Exposure to wood dust was associated with reduced risk of colon cancer that was partially masked before adjustment for confounders, and was limited to workers with frequent exposures that had begun at least 30 years before diagnosis [unadjusted and adjusted ORs, respectively, to exposures 5+ times a week beginning 30+ years before diagnosis = 0.63 (95% CI 0.36-1.13) and 0.39 (95% CI 0.20-0.77)]. This study provides additional evidence that heavy exposure to wood dusts may be associated with reduced risk of colon cancer in males after adjustment for other known causes of colon cancer.

Garabrant & Organochlorine Pesticides

"Increased odds ratios were observed for self-reported exposures to chloropropylate and DDT, as well as for the summary group of organochlorine pesticides which included all of these materials, though these associations were not significant."

Int J Cancer. 1997 Jul 3;72(1):62-7.
A case-control study of self-reported exposures to pesticides and pancreas cancer in southeastern Michigan.

Fryzek JP, Garabrant DH, Harlow SD, Severson RK, Gillespie BW, Schenk M, Schottenfeld D.
Department of Preventive and Societal Medicine, University of Nebraska Medical Center, Omaha 68198-4350, USA. jfryzek@mail.unmc.edu

A case-control study of pancreas cancer in residents, aged 30-79 years, of 18 counties in southeastern Michigan was conducted to investigate the risks of exposure to DDT and related materials in the general population. Sixty-six people with cytologically diagnosed pancreas cancer were identified using 7 participating hospitals in metropolitan Detroit and Ann Arbor. One hundred and thirty-one controls were frequency-matched to the cases on age, sex, ethicity and county of residence by random-digit dialing. All study participants were administered a questionnaire to assess life-time exposure to pesticides from both environmental and occupational sources, family history of cancer, past medical history, smoking history and demographic information. A statistically significant increased risk was found for self-reported exposure to ethylan (1,1-dichloro-2,2-bis(4-methoxyphenyl) ethane). Increased odds ratios were observed for self-reported exposures to chloropropylate and DDT, as well as for the summary group of organochlorine pesticides which included all of these materials, though these associations were not significant.
 

Garabrant & Silicon Breast Implants

"...we found no increased risk of SSc [systemic sclerosis] among women with silicone breast implants, equivocal evidence of risk from other silicone exposures, and no evidence of risk from silica exposure."
 

J Rheumatol. 1996 Nov;23(11):1904-11.
The epidemiology of scleroderma among women: assessment of risk from exposure to silicone and silica.

Burns CJ, Laing TJ, Gillespie BW, Heeringa SG, Alcser KH, Mayes MD, Wasko MC, Cooper BC, Garabrant DH, Schottenfeld D.
Department of Epidemiology, University of Michigan, Ann Arbor, USA.

OBJECTIVE: To investigate the relationship between exposure to silicone (including breast implants) and silica and the development of scleroderma (systemic sclerosis, SSc) among women. METHODS: A population based case-control study was conducted among women in Michigan. 274 confirmed cases of SSc diagnosed between 1985 and 1991 were identified by contacting rheumatologists, hospitals, and a scleroderma support group. These cases and 1184 controls were interviewed by telephone to ascertain past exposures to silicone or silica. RESULTS: Silicone in the form of breast implants was not associated with significantly increased risk of SSc (adjusted odds ratio, 1.30; 95% confidence interval, 0.27 to 6.23). Among 20 other potential silicone exposure surveyed, self-reported exposure to silicone based glues, sealants, and caulks, manufacture or repair of windows or windshields, repairing or frequently using photocopy machines, consumption of simethicone-containing antacids, and implanted medication delivery pumps were significantly associated with SSc. However, blinded assessment of all job and hobby descriptions in terms of their potential for silicone exposure failed to support the first 3 associations, antacid consumption may have been confounded by esophageal dysmotility before the diagnosis of SSc, and other silicone containing device categories (pacemakers, central nervous system shunts, other shunts and catheters) were not significantly associated with SSc. Surgically implanted metallic fixation devices were associated with significantly reduced risk for SSc. No association was detected between SSc and silica dust exposure. CONCLUSION: Consistent with other studies, we found no increased risk of SSc among women with silicone breast implants, equivocal evidence of risk from other silicone exposures, and no evidence of risk from silica exposure.
 

Garabrant & Nicotine Patches

"We conclude that transdermal nicotine patches are of limited efficacy in achieving long-term smoking cessation and that the relative costs and benefits of this treatment are not adequately specified."

J Occup Environ Med. 1996 Feb;38(2):184-9.
Effectiveness of nicotine patches in a workplace smoking cessation program. An eleven-month follow-up study.

Mankani SK, Garabrant DH, Homa DM.
Department of Family Medicine, Wayne State University, Detroit, Michigan 48201, USA.

Transdermal nicotine patches are widely prescribed as part of smoking cessation programs, but their efficacy beyond 6 months is not well established. We evaluated the efficacy of a 70-day treatment regimen among 75 subjects in an industrial setting where follow-up was conducted for 11 months. The median time free of cigarettes was 73 days, and the overall smoking abstinence rate was 9% after 11 months of follow-up. Smoking abstinence was significantly higher among those subjects who completed the full course of treatment than among those who did not (25 vs 6%, respectively). Smoking abstinence was also higher among subjects who started smoking after age 17 than among those who started at younger ages and was higher among male than female subjects. We conclude that transdermal nicotine patches are of limited efficacy in achieving long-term smoking cessation and that the relative costs and benefits of this treatment are not adequately specified.
 
 

Garabrant & Asbestos

"These results suggest that exposure to amphibole asbestos may be associated with colorectal cancer, but these findings may reflect an artifact of miscertification of cause of death. The results also suggest that serpentine asbestos is not associated with colorectal cancer."

Am J Epidemiol. 1994 Jun 15;139(12):1210-22.
A meta-analysis of colorectal cancer and asbestos exposure.

Homa DM, Garabrant DH, Gillespie BW.
Department of Environmental and Industrial Health, University of Michigan School of Public Health, Ann Arbor 48109-2029.

A meta-analysis of the relation between asbestos exposure and colorectal cancer mortality was conducted, using published reports of 20 asbestos-exposed cohorts. Summary standardized mortality ratios (SMRs) for colorectal cancer were examined in relation to asbestos type and estimates of dust exposure (as direct estimators of asbestos exposure) and in relation to lung cancer SMR and the proportion of all deaths due to mesothelioma (as proxy estimators of asbestos exposure). An elevated summary SMR was observed in cohorts exposed to amphibole asbestos (summary SMR = 1.47; 95% confidence interval (CI) 1.09-2.00), but not in cohorts exposed to serpentine asbestos (summary SMR = 1.04; 95% CI 0.81-1.33) or in cohorts exposed to both serpentine and amphibole asbestos (summary SMR = 1.03; 95% CI 0.74-1.42). Cohorts having a lung cancer SMR greater than 2.00 had a summary SMR of 1.51 (95% CI 1.29-1.76), and cohorts in which more than 1% of all deaths were attributed to mesothelioma had a summary SMR of 1.24 (95% CI 0.94-1.64). After stratifying the cohorts based on mortality due to all cancers excluding those known or suspected to be associated with asbestos exposure, lung cancer mortality was not clearly associated with colorectal cancer mortality, suggesting that the crude association between these factors may be due to misdiagnosis of lung cancer as other types of cancer in the reported causes of death. These results suggest that exposure to amphibole asbestos may be associated with colorectal cancer, but these findings may reflect an artifact of miscertification of cause of death. The results also suggest that serpentine asbestos is not associated with colorectal cancer.
 

"This study suggests not only that occupational exposure to asbestos is not a risk factor for colon cancer in the general population of Los Angeles, but also that observed associations between asbestos and colon cancer should not be interpreted as causal unless confounding by nonoccupational factors has been evaluated and controlled."

Am J Epidemiol. 1992 Apr 15;135(8):843-53.  Related Articles, Links
Asbestos and colon cancer: lack of association in a large case-control study.

Garabrant DH, Peters RK, Homa DM.
Department of Environmental and Industrial Health, University of Michigan School of Public Health, Ann Arbor.
Previous studies linking exposure to asbestos with human colon cancer have used mortality rather than incidence as their endpoint and have neither assessed nor controlled for confounding by diet, genetic factors, or other risk factors for colon cancer. A case-control study of 746 histologically confirmed cases of colon cancer and 746 matched neighborhood controls was conducted in Los Angeles County, California. In univariate analyses of the 419 male pairs, a weak association was found between asbestos exposure and colon cancer (odds ratio (OR) = 1.16, 95% confidence interval (CI) 0.80-1.69). When confounding by family history of large bowel cancer, diet, body weight, and physical activity was controlled, there was no association between colon cancer and exposure to asbestos among males (OR = 0.99, 95% CI 0.66-1.50). When asbestos exposure was restricted to occurrences preceding diagnosis by more than 15 years, there was no clear association between such exposure and colon cancer, either before (OR = 1.14, 95% CI 0.76-1.70) or after confounding was controlled (OR = 0.93, 95% CI 0.60-1.44). Further analyses by frequency and duration of exposure failed to show any association between asbestos and risk of colon cancer, but did show a consistent pattern of confounding by nonoccupational factors that, when controlled, invariably produced a weak protective effect of asbestos exposure. Among the 327 female pairs, only 6 cases and 11 controls reported asbestos exposure (OR = 0.55, 95% CI 0.20-1.48), and there was no evidence of risk increasing as the frequency or duration of exposure increased. This study suggests not only that occupational exposure to asbestos is not a risk factor for colon cancer in the general population of Los Angeles, but also that observed associations between asbestos and colon cancer should not be interpreted as causal unless confounding by nonoccupational factors has been evaluated and controlled.
 
 

Garabrant & Occupational Cancer

"Investigation of cancer clusters often presents a difficult scientific challenge, which requires careful case ascertainment, calculations of risk based on an appropriate reference population, identification of distant past exposures, and a search for common elements among the cases."

Prim Care. 1994 Jun;21(2):329-47.
Occupational cancer.

Patellos MC, Garabrant DH.
Department of Environmental and Industrial Health, University of Michigan, School of Public Health, Ann Arbor.

Occupational exposures are important contributors to the total burden of cancer in the United States. No histologic features distinguish occupational cancer from that due to other causes. The IARC provides a systematic framework for evaluating the evidence linking occupational exposures to human cancer and publishes summary monographs which detail the strength of evidence for approximately 732 agents evaluated to date. These monographs are one of the most reliable reference sources for practitioners who must answer questions regarding cancer risk to working populations. The diagnosis of occupational cancer must be based on a systematic approach in which the diagnosis of cancer is confirmed, the exposures of the patient are defined and quantified, and the scientific evidence regarding the risk from such exposures is evaluated. Cancer screening programs in work settings are difficult to justify based on scientific principles and must be adapted to the circumstances of exposure and to meet legal requirements for medical surveillance, if they are to be performed at all. Investigation of cancer clusters often presents a difficult scientific challenge, which requires careful case ascertainment, calculations of risk based on an appropriate reference population, identification of distant past exposures, and a search for common elements among the cases. Negative and equivocal findings are common, and it is important for investigators to be able to demonstrate the scientific rigor of their approach in resolving these issues.