2,4,5-Trichlorophenoxyacetic acid (2,4,5-T)
- 2,4-Dichlorophenoxyacetic acid (2,4-D)
- 2 methyl-4 chlorophenoxyacetic acid
- Agent Orange
Studies and Reports
- Boers D et al., Cause-specific mortality of Dutch chlorophenoxy herbicide manufacturing workers, Occup Environ Med. 2010 Jan;67(1):24-31. Epub 2009 Sep 6.
- Results and Conclusion. "RESULTS: Previously reported increased risks for respiratory cancer, non-Hodgkin's lymphoma and ischaemic heart disease in factory A could not be confirmed in the present analysis. However, increased risks were observed for all cancers in both factory A (hazard ratio (HR) 1.31; 95% CI 0.86 to 2.01) and factory B (HR 1.54; 95% CI 1.00 to 2.37). Increased risks for urinary cancers (HR 4.2; 95% CI 0.99 to 17.89) and genital cancers (HR 2.93; 95% CI 0.61 to 14.15) were observed in factory A, consistent with earlier reported results in this population. More detailed analyses showed that this increased risk for urinary and genital cancers in exposed workers was not due to selection of healthy controls and could not be attributed to specific products or departments. CONCLUSION: The results of this study showed only slight increases in cancer mortality risk. The increased risk for urinary cancers is noteworthy, but could not be linked to a specific exposure and needs to be confirmed in similar cohorts.
- Comment. None of the reported associations for cancer mortality risk attained statistical significance.
- Reed D et al., Cancer incidence and mortality in a New Zealand community potentially exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin from 2,4,5-trichlorophenoxyacetic acid manufacture, Aust N Z J Public Health. 2007 Feb;31(1):13-8.
- Conclusion. "The results do not suggest an increased cancer risk among the New Plymouth population related to the period of 2,4,5-T manufacture, although the study's limitations mean the possibility of an undetectable small elevation in cancer risk cannot be excluded. Although TCDD exposure in the first few years of 2,4,5-T manufacture may have contributed to cancer incidence in 1970-74, unknown exposure(s) before the start of 2,4,5-T manufacture and chance are also possible explanations."
- Fleming L et al., Mortality in a cohort of licensed pesticide applicators in Florida, Occup Environ Med. 1999 Jan;56(1):14-21.
- Results and Conclusions. RESULTS: The pesticide applicators were consistently and significantly healthier than the general population of Florida. As with many occupational cohorts, the risks of cardiovascular disease and of diseases associated with alcohol and tobacco use were significantly lower, even in the subpopulations--for example, men, women, and licence subcategories. Among male applicators, prostate cancer mortality (SMR 2.38 (95% confidence interval (95% CI) 1.83 to 3.04) was significantly increased. No cases of soft tissue sarcoma were confirmed in this cohort, and non-Hodgkin's lymphoma was not increased. The number of female applicators was small, as were the numbers of deaths. Mortality from cervical cancer and breast cancer was not increased. Additional subcohort and exposure analyses were performed. CONCLUSIONS: Consistent with previous publications on farmers but at odds with current theories about the protective effects of vitamin D, prostate cancer was increased in these pesticide applicators. Female breast cancer was not increased despite theories linking risk of breast cancer with exposure to oestrogen disruptors--such as the organochlorines. The lack of cases of soft tissue sarcoma is at odds with previous publications associating the use of the phenoxy herbicides with an increased risk of these cancers."
- Asp S et al., Mortality and cancer morbidity of Finnish chlorophenoxy herbicide applicators: an 18-year prospective follow-up, Am J Ind Med. 1994 Aug;26(2):243-53.
- Abstract. "An 18-year follow-up for mortality and cancer morbidity was conducted in a cohort of 1,909 men who had started spraying chlorophenoxy herbicides (mixture of 2,4-dichlorophenoxyacetic acid [2,4-D] and 2,4,5-trichlorophenoxyacetic acid [2,4,5-T]) in 1955 through 1971. In all, 384 persons had died during the follow-up, and there was a slight deficit in natural deaths (standardized mortality ratio [SMR] 0.84; 95% confidence interval [CI] 0.75-0.94). By contrast, there was a small, nonsignificant increase in accidental and violent deaths. The overall cancer mortality was slightly less than in the general population (SMR 0.83; 95% CI 0.65-1.02), and not a single case of death of non-Hodgkin's lymphomas (NHL) or soft tissue sarcomas (STS) was detected. With regard to cancer morbidity, the incident cases showed a slight deficit compared to the population figure (standardized incidence ratio [SIR] 0.81; 95% CI 0.67-0.97). One case of NHL was found (2.4 expected with 10 years of latency), but not a single case of STS (0.8 expected with 10 years of latency). While our study does not support the contention that spraying of 2,4-D and 2,4,5-T containing herbicides carries any significant risk of cancer, the medium to low statistical power of the study does not allow any far reaching negative conclusions regarding the carcinogenicity of the agents."
- Kogevinas M et al., Cancer incidence and mortality in women occupationally exposed to chlorophenoxy herbicides, chlorophenols, and dioxins, Cancer Causes Control. 1993 Nov;4(6):547-53.
- Abstract. "The association between exposure to chlorophenoxy herbicides contaminated with dioxins and occurrence of cancer has been studied mainly in male populations. In animal experiments, gender differences have been recorded in the cancer response to administered 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mortality and cancer incidence in an international cohort of 701 women from an International Register of Workers occupationally exposed to chlorophenoxy herbicides, chlorophenols, and dioxins is examined. Cause-specific, national death rates and cancer incidence rates were used as referents. Cancer risk was not increased overall, with a standardized incidence ratio (SIR) of 96 and 95 percent confidence interval (CI) of 64-137, based on 29 cases. Among workers exposed to those chlorophenoxy herbicides contaminated with TCDD, excess cancer incidence (for all sites) was observed (SIR = 222, CI = 102-422, 9 cases); this was highest in the first 10 years after exposure. No excess was observed for breast cancer, the most common cancer in this cohort. Results on cancer mortality were consistent with those on incidence."
- Bueno de Mesquita H et al., Occupational exposure to phenoxy herbicides and chlorophenols and cancer mortality in The Netherlands, Am J Ind Med. 1993 Feb;23(2):289-300.
- Abstract. "As part of the "IARC International Register of Persons Exposed to Phenoxy Herbicides and Contaminants," a cohort of workers who manufacture and prepare chlorophenoxy herbicides was recruited in The Netherlands. The cohort comprised 2,310 workers from two plants, operated by different companies, who were followed during the periods 1955-1985 and 1965-1986, respectively. In 1963, there had been an industrial accident in one factory with concomitant release of dioxin into the environment. Loss to follow-up was 3%. Mortality data on 963 exposed and 1,111 nonexposed men were evaluated by external and internal comparison. Compared with national rates, total mortality (94 deaths, standardized mortality ratio [SMR] = 101; 95% confidence interval [CI], 82-124) and cancer mortality (31 deaths, SMR = 107; 95% CI, 73-152) for exposed workers were not significantly increased. A statistically insignificant increase was observed for non-Hodgkin's lymphoma (2 deaths, SMR = 299; 95% CI, 36-1,078). No cases of soft-tissue sarcoma were encountered. There was no increase in either total mortality (25 deaths, SMR = 111; 95% CI, 72-163) or cancer mortality (10 deaths, SMR = 137; 95% CI, 66-252) among the 139 workers probably exposed to dioxins during the 2,4,5-trichlorophenol production accident or the subsequent clean-up operations. Compared with nonexposed workers, exposed workers did not exhibit a higher total mortality (rate ratio [RR] = 1.28; 95% CI, 0.89-1.82). Mortality due to all cancers (RR = 1.7; 95% CI, 0.9-3.4) and respiratory cancer (RR = 1.7; 95% CI, 0.5-6.3) was insignificantly elevated. These findings suggest that the increases in cancer mortality among workers exposed to phenoxy herbicides and chlorophenols may be attributable to chance. Lack of power prevented evaluation with respect to specific cancers."
- Saracci R et al., Cancer mortality in workers exposed to chlorophenoxy herbicides and chlorophenols, Lancet. 1991 Oct 26;338(8774):1027-32.
- Abstract. "Epidemiological studies have revealed an increased risk of cancer, notably soft-tissue sarcomas and non-Hodgkin's lymphomas, in people occupationally exposed to chlorophenoxy herbicides, including those contaminated by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). We report here a historical cohort study of mortality in an international register of 18,910 production workers or sprayers from ten countries. Exposure was reconstructed through questionnaires, factory or spraying records, and job histories. Cause-specific national death rates were used as reference. No excess was observed in all-cause mortality, for all neoplasms, for the most common epithelial cancers, or for lymphomas. A statistically non-significant two-fold excess risk, based on 4 observed deaths, was noted for soft-tissue sarcoma with a standardised mortality ratio (SMR) of 196 and 95% confidence interval (Cl) 53-502; this was concentrated as a six-fold statistically significant excess, occurring 10-19 years from first exposure in the cohort as a whole (SMR = 606 [165-1552]) and, for the same time period, as a nine-fold excess among sprayers (SMR = 882 [182-2579]). Risks appeared to be increased for cancers of the testicle, thyroid, other endocrine glands, and nose and nasal cavity, based on small numbers of deaths. The excess of soft-tissue sarcomas among sprayers is compatible with a causal role of chlorophenoxy herbicides but the excess does not seem to be specifically associated with those herbicides probably contaminated by TCDD."
- Smith A et al., [http://www.ncbi.nlm.nih.gov/pubmed/1735875 Serum 2,3,7,8-tetrachlorodibenzo-p-dioxin levels of New Zealand pesticide applicators and their implication for cancer hypotheses J Natl Cancer Inst. 1992 Jan 15;84(2):104-8.
- Abstract. "On the basis of our findings in these subjects in New Zealand, we conclude that increased risks of cancer from brief exposure to phenoxyherbicides reported in other countries are probably not attributable to the TCDD that contaminates 2,4,5-T. We cannot determine from these results, however, whether TCDD exposure from prolonged use of 2,4,5-T poses significant health risks."
- Bond G et al., Phenoxy herbicides and cancer: insufficient epidemiologic evidence for a causal relationship, Fundam Appl Toxicol. 1989 Jan;12(1):172-88.
- Abstract. "The question as to whether or not any or all of the phenoxy herbicides are carcinogenic to humans continues to be evaluated. We review the evidence available from the retrospective cohort and case-control epidemiology studies. Graphs of the individual probability densities for the odds ratios from the eight case-control studies of soft-tissue sarcoma, Hodgkin's disease, or non-Hodgkin's lymphoma demonstrate gross inconsistencies which are not likely to be attributable to chance. Early studies, conducted in Sweden, had indicated strong associations, but subsequent work from New Zealand and the United States has failed to substantiate those findings. The reasons for the discordant results may relate more to methodologic problems in the earlier studies than to qualitative or quantitative differences in the exposures of the underlying populations. The retrospective cohort studies offer the advantage of having focused on occupational groups believed to have had the highest exposures, although they have been criticized as being individually too small to assess the risks of the rarer forms of cancer. Consideration of the combined cohort studies of workers exposed to the phenoxy herbicides per se provides little or no evidence of carcinogenicity. Thus, the total weight of evidence currently available does not support a conclusion that the phenoxy herbicides present a carcinogenic hazard to humans."
- Vineis P et al., Phenoxy herbicides and soft-tissue sarcomas in female rice weeders. A population-based case-referent study, Scand J Work Environ Health. 1987 Feb;13(1):9-17.
- Abstract. "A population-based case-referent study was conducted in an area of northern Italy where rice growing is the predominant agricultural activity and phenoxy herbicides have been used since 1950. Manual rice weeding was formerly performed by a seasonal female working population; in the early 1950s these women were concurrently exposed to chemical herbicides. Sixty-eight persons representing incident and histologically revised cases (31 women) and 158 population referents (73 women) were interviewed. The cases were histologically confirmed independently by two blinded pathologists, and exposure to phenoxy herbicides was assessed by two blinded pesticide researchers. An age-adjusted odds ratio of 0.91 was found for the living men (with suspect exposures; no man diagnosed as a case had been exposed with certainty to phenoxy herbicides). Among the living women the relative risk was 2.7 (90% confidence interval 0.59-12.37), and it further increased when attention was restricted to women exposed in the whole 1950-1955 period and to younger age groups.
- Pearn J, Herbicides and congenital malformations: a review for the paediatrician, Aust Paediatr J. 1985 Nov;21(4):237-42.
- Abstract. "The herbicides 2, 4, 5-T and 2, 4-D are relatively non-toxic to primates, in acute exposure. Dioxins, which have occurred as impurities in these two herbicides, manifest universal biological toxicity. The best understood dioxin TCDD, has, in susceptible strains of mice, a very low teratogenic minimal effective dose of 1-10 micrograms/kg. This fact has engendered an era of uncertainty about the potential teratogenic effects of herbicides, in the context of potential human exposure. This paper reviews current knowledge concerning herbicide teratogenesis following maternal exposure. Because of species specificity of teratogenic agents, it is not possible to extrapolate from effects in lower animals to potential effects in humans. It remains a fact however that all proven human teratogens have parallel animal models. Following maternal exposure to herbicides and to dioxins, it has not been possible to produce teratogenic effects in primates, although fertility may be affected. Epidemiological reports from Hungary, Italy (the ICMESA accident), New Zealand, the United States, Europe and Australia have not revealed any positive evidence to indicate that a human herbicide teratogenic syndrome exists."
- Smith A et al., Soft tissue sarcoma and exposure to phenoxyherbicides and chlorophenols in New Zealand, J Natl Cancer Inst. 1984 Nov;73(5):1111-7.
- Abstract. "Phenoxyherbicides, including (2,4,5-trichlorophenoxy)acetic acid (CAS: 93-76-5), have been widely used in New Zealand for over 30 years. In the light of Swedish studies reporting an association between exposure to phenoxyherbicides or chlorophenols and soft tissue sarcoma, a case-control study was undertaken that involved interviewing 82 subjects (cases) with soft tissue sarcoma and 92 controls with other types of cancer. For those potentially exposed to phenoxyherbicides for more than 1 day not in the 5 years before cancer registration, the estimate of relative risk was 1.3, with 90% confidence limits of 0.6-2.5. The comparable relative risk estimate for chlorophenol exposure was 1.5, with 90% confidence limits of 0.5-4.5. The discovery of cases in trichlorophenol manufacturing plants in the United States lended support to the Swedish findings, but further studies are needed to conclude whether human exposure to these chemicals truly increases the risk of soft tissue sarcoma."
- Suskind R and Hertzberg V, Human health effects of 2,4,5-T and its toxic contaminants, JAMA. 1984 May 11;251(18):2372-80.
- Abstract. "A clinical epidemiologic study was conducted to determine the long-term health effects of workplace exposure to the process of manufacturing the herbicide (2,4,5-trichlorophenoxy)acetic acid including contaminants such as 2,3,7,8-tetrachlorodibenzo-rho-dioxin. The population consisted of two cohorts: 204 clearly exposed and 163 not exposed. Among the exposed, clinical evidence of chloracne persisted in 55.7%. None of the not exposed experienced chloracne development. An association was found between the persistence of chloracne and the presence and severity of actinic elastosis of the skin. There is an association between exposure and the history of gastrointestinal tract ulcer. Pulmonary function values among those who were exposed and who currently smoked were lower than those who were not exposed and who currently smoked. The data assembled in the study indicate no evidence of increased risk for cardiovascular disease, hepatic disease, renal damage, or central or peripheral nervous system problems."
- Smith A et al., Congenital defects and miscarriages among New Zealand 2, 4, 5-T sprayers, Arch Environ Health. 1982 Jul-Aug;37(4):197-200.
- Abstract. [A survey was conducted of professional New Zealand 2, 4, 5-T sprayers and a comparison group of agricultural contractors with a total of 989 respondents. The numbers of births, congenital defects, and miscarriages were identified from 1969 to 1980 by a postal questionnaire. Each pregnancy outcome was classified according to whether or not the father sprayed 2,4,5-T during the year of the pregnancy outcome, or the previous year. The relative risk estimates of 1.19 for congenital defects, and 0.89 for miscarriages, were not statistically significant. These results are reassuring as far as male professional 2,4,5-T sprayers are concerned. In addition, the extent of exposure of their wives from helping with spray activities, and from washing contaminated clothes, has not had a detectable reproductive effect."
- Riihimaki V et al., Mortality of 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid herbicide applicators in Finland: first report of an ongoing prospective cohort study, Scand J Work Environ Health. 1982 Mar;8(1):37-42.
- Abstract. "Some recent epidemiologic studies have suggested that chlorinated phenoxy acid herbicides are human carcinogens. The mortality experience in a cohort of 1,926 men who had sprayed 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) during 1955-1971 has been followed prospectively from 1972 to 1980. The total phenoxy acid exposure was generally rather low because the duration of work had mostly been less than two months. In 1972-1976 mortality from all natural causes in the cohort was only 54% of the expected value (based on age-specific rates for the general population), and in the succeeding 4-a period 81% of the expected value. In the assessment of cancer, mortality allowance was made for 10- and 15-a periods of latency between the first exposure and the start of the recording of vital status during the follow-up. No increase in cancer mortality was detected, and the distribution of cancer types was unremarkable. No cases of death from lymphomas or soft tissue sarcomas were found. The study results must, however, be viewed with great caution owing to the small size of the cohort, the low past exposure, and the brief follow-up period."
- Ott M et al., A mortality analysis of employees engaged in the manufacture of 2,4,5-trichlorophenoxyacetic acid, J Occup Med. 1980 Jan;22(1):47-50.
- Abstract. "There have been few published reports regarding surveillance of individuals occupationally exposed to 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). The present study examined the mortality experience of 204 persons exposed to 2,4,5-T during its manufacture from 1950 to 1971. Length of employment in job assignments within the 2,4,5-T process area ranged from less than one year to a maximum of approximately ten years. Efforts to minimize 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) contamination of the product resulted in nondetectable concentrations using a method of detection developed in 1966 that was sensitive to 1 part per million. Within the scope of this mortality survey, no adverse effects were observed with respect to occupational exposure to 2,4,5-T or its feedstock, 2,4,5-trichlorophenol."
- Facts Versus Fears (Fourth Edition) A Review of the Greatest Unfounded Health Scares of Recent Times, American Council on Science and Health, September 28, 2004.
- Gough M, Testimony before the Committee on Veterans' Affairs, United States Senate, Herbicide Exposure: Link to Disease, Cato.org, September 19. 1996.