Mortality in chemical workers potentially exposed to 2,4-dichlorophenoxyacetic acid (2,4-D) 1945–94: an update

OBJECTIVE To update and add to a previously identified cohort of employees potentially exposed to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). The putative association between 2,4-D and non-Hodgkin's lymphoma has been debated for more than a decade. METHODS Cohort members were male employees of The Dow Chemical Company who manufactured or formulated 2,4-D any time from 1945 to the end of 1994. Their mortality experience was compared with national rates and with more than 40 000 other company employees who worked at the same location. RESULTS 330 Deaths were observed among 1517 people compared with 365 expected (standardised mortality ratio (SMR)=0.90, 95% confidence interval (95% CI) 0.81 to 1.01). There were no significantly increased SMRs for any of the causes of death analyzed. When compared with the United States rates, the SMR for non-Hodgkin's lymphoma (NHL) was 1.00 (95% CI 0.21 to 2.92). The internal comparison with other Dow employees showed a non-significant relative risk of 2.63, (95% CI 0.85 to 8.33). Death was attributed to amyotrophic lateral sclerosis (ALS) for three cohort members. Compared with the other company employees, the relative risk was 3.45 (95% CI 1.10 to 11.11). The cases were employed in the manufacture or formulation of 2,4-D at different periods (1947–9, 1950–1, and 1968–86), and for varying durations of time (1.3, 1.8, and 12.5 years). CONCLUSION There was no evidence of a causal association between exposure to 2,4-D and mortality due to all causes and total malignant neoplasms. No significant risk due to NHL was found. Although not an initial hypothesis, an increased relative risk of ALS was noted. This finding is unsupported by other animal and human studies.

[1]  J. Kaneene,et al.  Re-analysis of 2,4-D use and the occurrence of canine malignant lymphoma. , 1999, Veterinary and human toxicology.

[2]  L. Fleming,et al.  Mortality in a cohort of licensed pesticide applicators in Florida. , 1999, Occupational and environmental medicine.

[3]  K. Steenland,et al.  NIOSH life table program for personal computers. , 1998, American journal of industrial medicine.

[4]  Icmje Icmje,et al.  UNIFORM REQUIREMENTS FOR MANUSCRIPTS SUBMITTED TO BIOMEDICAL JOURNALS , 2000 .

[5]  E. Lynge,et al.  Cancer incidence in Danish phenoxy herbicide workers, 1947-1993. , 1998, Environmental health perspectives.

[6]  B. Yano,et al.  Single-dose and chronic dietary neurotoxicity screening studies on 2,4-dichlorophenoxyacetic acid in rats. , 1997, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[7]  S. Zahm,et al.  Mortality study of pesticide applicators and other employees of a lawn care service company. , 1997, Journal of occupational and environmental medicine.

[8]  G. Belle,et al.  Occupational exposures and amyotrophic lateral sclerosis. A population-based case-control study. , 1997, American journal of epidemiology.

[9]  M. Dosemeci,et al.  Residential and occupational exposure to sunlight and mortality from non-Hodgkin's lymphoma: composite (threefold) case-control study , 1997, BMJ.

[10]  A. Blair,et al.  Pesticides and cancer. , 1997, Occupational medicine.

[11]  G. Olsen,et al.  A thirty-eight year comparison of cancer incidence and mortality among employees at a Connecticut chemical plant. , 1997, Connecticut medicine.

[12]  A. Faustini,et al.  Immunological changes among farmers exposed to phenoxy herbicides: preliminary observations. , 1996, Occupational and environmental medicine.

[13]  G. Román,et al.  Neuroepidemiology of amyotrophic lateral sclerosis: clues to aetiology and pathogenesis. , 1996, Journal of neurology, neurosurgery, and psychiatry.

[14]  G. Olsen,et al.  The Effect of the Type of Respondent on Risk Estimates of Pesticide Exposure in a Non-Hodgkin's Lymphoma Case-Control Study , 1996 .

[15]  L. Fuortes,et al.  Proportionate mortality study of golf course superintendents. , 1996, American journal of industrial medicine.

[16]  P. Hartge,et al.  Non-Hodgkin's lymphoma and sunlight. , 1996, Journal of the National Cancer Institute.

[17]  N. Mueller Another view of the epidemiology of non-Hodgkin's lymphoma. , 1994, Oncology.

[18]  H. Morrison,et al.  Non-Hodgkin's lymphoma and agricultural practices in the prairie provinces of Canada. , 1994, Scandinavian journal of work, environment & health.

[19]  J. Mandel,et al.  An update of mortality among chemical workers potentially exposed to the herbicide 2,4-dichlorophenoxyacetic acid and its derivatives. , 1993, Journal of occupational medicine. : official publication of the Industrial Medical Association.

[20]  J. Slattery,et al.  Risk factors for motor neuron disease: a case-control study based on patients from the Scottish Motor Neuron Disease Register. , 1993, Journal of neurology, neurosurgery, and psychiatry.

[21]  R. A. Johnson,et al.  Data on Prior Pesticide Use Collected from Self‐and Proxy Respondents , 1993, Epidemiology.

[22]  I. Munro,et al.  A Comprehensive, Integrated Review and Evaluation of the Scientific Evidence Relating to the Safety of the Herbicide 2,4-D , 1992 .

[23]  E F Heineman,et al.  Clues to cancer etiology from studies of farmers. , 1992, Scandinavian journal of work, environment & health.

[24]  L. Brown,et al.  Pesticides and other agricultural risk factors for non-Hodgkin's lymphoma among men in Iowa and Minnesota. , 1992, Cancer research.

[25]  R. Tarone,et al.  Case-control study of canine malignant lymphoma: positive association with dog owner's use of 2,4-dichlorophenoxyacetic acid herbicides. , 1991, Journal of the National Cancer Institute.

[26]  L. Green A cohort mortality study of forestry workers exposed to phenoxy acid herbicides. , 1991, British journal of industrial medicine.

[27]  P. Winter,et al.  Mortality and incidence of cancer at four factories making phenoxy herbicides. , 1991, British journal of industrial medicine.

[28]  D. Weisenburger,et al.  A Case‐Control Study of Non‐Hodgkin's Lymphoma and the Herbicide 2,4‐Dichlorophenoxyacetic Acid (2, 4‐D) in Eastern Nebraska , 1990, Epidemiology.

[29]  N. Pearce,et al.  Latency analysis in occupational epidemiology. , 1990, Archives of environmental health.

[30]  N. Pearce Phenoxy herbicides and non-Hodgkin's lymphoma in New Zealand: frequency and duration of herbicide use. , 1989, British journal of industrial medicine.

[31]  D. Austin,et al.  Use of a population-based tumor registry to estimate cancer incidence among a cohort of chemical workers. , 1988, Journal of Occupational Medicine.

[32]  G. Bond,et al.  Cause specific mortality among employees engaged in the manufacture, formulation, or packaging of 2,4-dichlorophenoxyacetic acid and related salts. , 1988, British journal of industrial medicine.

[33]  R. Severson,et al.  Soft tissue sarcoma and non-Hodgkin's lymphoma in relation to phenoxyherbicide and chlorinated phenol exposure in western Washington. , 1987, Journal of the National Cancer Institute.

[34]  G. Landry,et al.  Attractive method for battery removal. , 1986, Journal of the American Medical Association (JAMA).

[35]  R. Hoover,et al.  Agricultural herbicide use and risk of lymphoma and soft-tissue sarcoma. , 1986, JAMA.

[36]  B. Blakley,et al.  The effect of topically applied n‐butylester of 2,4‐dichlorophenoxyacetic acid on the immune response in mice , 1986, Journal of applied toxicology : JAT.

[37]  B. Henderson,et al.  A case-control study of amyotrophic lateral sclerosis. , 1986, American journal of epidemiology.

[38]  B. Blakley,et al.  The effect of prenatal exposure to the n-butylester of 2,4-dichlorophenoxyacetic acid (2,4-D) on the immune response in mice. , 1986, Teratology.

[39]  T. Hakulinen A Mantel-Haenszel statistic for testing the association between a polychotomous exposure and a rare outcome. , 1981, American journal of epidemiology.

[40]  M. Eriksson,et al.  Malignant lymphoma and exposure to chemicals, especially organic solvents, chlorophenols and phenoxy acids: a case-control study. , 1981, British Journal of Cancer.

[41]  K. Austen,et al.  Cold urticaria: release into the circulation of histamine and eosinophil chemotactic factor of anaphylaxis during cold challenge. , 1976, The New England journal of medicine.

[42]  R. Monson,et al.  Analysis of relative survival and proportional mortality. , 1974, Computers and biomedical research, an international journal.

[43]  Nathan Mantel,et al.  Chi-square tests with one degree of freedom , 1963 .

[44]  D. Dalgard,et al.  Comparative subchronic and chronic dietary toxicity studies on 2,4-dichlorophenoxyacetic acid, amine, and ester in the dog. , 1996, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[45]  W. Stott,et al.  Chronic dietary toxicity/oncogenicity studies on 2,4-dichlorophenoxyacetic acid in rodents. , 1996, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[46]  Lorene M. Nelson,et al.  Epidemiology of ALS. , 1995, Clinical neuroscience.

[47]  G. Savettieri,et al.  A case-control study of amyotrophic lateral sclerosis. , 1991, Neuroepidemiology.

[48]  G. Bond,et al.  Cause-specific mortality among male chemical workers. , 1987, American journal of industrial medicine.

[49]  B. Blakley The effect of oral exposure to the n-butylester of 2,4-dichlorophenoxyacetic acid on the immune response in mice. , 1986, International journal of immunopharmacology.