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Reference | Evaluation | Conclusions |
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Regulatory reviews or reviews in support of regulatory activities |
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US EPA, SAB [27] | Science Advisory Board consultation on carcinogenicity of 2,4-D | “Data are not sufficient to conclude that there is a cause and effect relationship between exposure to 2,4-D and non-Hodgkin’s lymphoma.” |
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US EPA [28] | 4th carcinogenicity of 2,4-D peer review | Not classifiable as to carcinogenicity. |
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WHO/IARC [29] | Evaluations of carcinogenic risk | Inadequate and/or limited for 2,4-D specifically and chlorophenoxy compounds generally. |
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US EPA [5] | Health Effects Division Carcinogenicity Peer Review Committee (2,4-D) | “Evidence is inadequate and cannot be interpreted as showing either the presence or absence of a carcinogenic effect.” |
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European Commission [30] | Review report for 2,4-D | Proposed uses have no harmful effects on animal or human health; no evidence of carcinogenicity. |
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US EPA [3, 4] | Risk assessments and reregistration decision for MCPA | Limited evidence for carcinogenicity. |
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US EPA [8] | Risk assessments and reregistration decision for 2,4-D | Group D, not classifiable as to carcinogenicity. |
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Health Canada PMRA [31] | Reregistration decision for 2,4-D | No evidence of carcinogenicity. |
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Health Canada PMRA [32] | Reregistration decision for MCPA | No evidence of carcinogenicity. |
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Health Canada [9] | MCPA in drinking water | Not considered a carcinogen. |
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77FR23135 [33] | Response to NRDC petition to revoke 2,4-D registration | No new evidence that would suggest registration should be revoked. |
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Nonregulatory reviews |
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Canadian Centre for Toxicology [34] | Expert panel on carcinogenicity of 2,4-D | No evidence that 2,4-D forms reactive intermediates in the liver or other tissues or forms adducts with DNA. Existing animal and human data are insufficient to support the finding that 2,4-D is a carcinogen; insufficient evidence that existing uses of 2,4-D pose a significant human health risk. |
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Kelly and Guidotti [35] | Review of literature to advise provincial regulatory body on chlorophenoxy safety, particulary 2,4-D | Evidence for a causal association is strongest for NHL and probably reflects either a weak effect or, possibly, a confounding exposure associated with the use of 2,4-D. Given worst-case assumptions, potency of 2,4-D as a carcinogen is probably weak. Its intrinsic toxicity is less than that of alternative herbicides. |
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Johnson [36, 36] | 13 cohort studies (9 cohorts) in chlorophenoxy manufacturing; 16 cohort studies (12 cohorts) in chlorophenoxy spraying | The weight of evidence does not unequivocally support an association between use of chlorophenoxys and malignant lymphomas/STS; occupational cohort studies have not accumulated sufficient person-years of observation to date, yet see cases of myeloid lymphoma and STS when none are expected. |
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Ibrahim et al. [37] | Human carcinogenicity of 2,4-D | The toxicological data alone do not provide a strong basis for determination of carcinogenicity of 2,4-D. Suggestive although inconclusive evidence for an association between exposure to 2,4-D and NHL based on epi studies and further study was warranted. Little evidence of an association between 2,4-D and STS or HD, and no evidence of an association between 2,4-D use and any other form of cancer. |
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Munroe et al. [38] | Comprehensive, integrated review of 2,4-D safety in humans | No evidence for adverse health effects; no mechanistic basis by which 2,4-D could cause cancer. |
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Morrison et al. [14] | Meta analysis of epidemiological studies involving occupational exposures to chlorophenoxy compounds | Suggestive evidence of an association with NHL; no evidence for an association with STS, HD, or leukemia. |
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Bond and Rossbacher [39] | Potential carcinogenicity of MCPA, MCPP, 2,4-DP | No evidence for carcinogenicity across all three compounds. |
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Henschler and Greim [40] | Comprehensive, integrated review to establish “maximale arbeitsplatz konzentration” | Evidence for potential proliferative response; less evidence for genotoxicity. |
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Gandhi et al. [41] | Potential carcinogenicity of 2,4-D | Some suggestive evidence for an association with NHL but without any plausible mode of action. |
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Garabrant and Philbert [42] | Comprehensive, integrated review of potential for health effects in humans | No causal association of any form of cancer with 2,4-D exposure. Animal studies of acute, subchronic, and chronic exposure to 2,4-D, its salts, and esters showed an unequivocal lack of systemic toxicity at doses that did not exceed renal clearance mechanisms. No evidence that 2,4-D in any of its forms activated or transformed the immune system in animals at any dose. |
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Bus and Hammond [43] | Update on data generated by the Industry Task Force II on 2,4-D Research Data | Toxicity responses limited to highest doses; not a carcinogen or genotoxicant, does not cause birth defects; low potential for reproductive toxicity and neurotoxicity. |
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Van Maele-Fabry et al. [44] | Cohort studies for chlorophenoxy expousures and leukemia | Meta-analysis of 3 cohort studies; statistically significant odds ratio = 1.60, 95% confidence interval = 1.02–2.52; all three underlying studies individually showed non-significant associations. |
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