Case-control studies chlorophenols

Hardell L, Eriksson M, Lenner P, et al. 1981. Malignant lymphoma and exposure to chemicals, especially organic solvents, chlorophenols and phenoxy acids A case-control study. Br J Cancer 43 169-176. 

J.D., Neuberg, M., Benn, T, Fannett, B., Pearce, N. Saracci, R. (1995) Soft tissue sarcoma and non-Hodgkin s lymphoma in workers exposed to phenoxy herbicides, chlorophenols, and dioxins two nested case-control studies. Epidemiology, 6, 396-402... 

Associations with chlorophenols were, however, analysed in two case-control studies nested within 24 of the 36 cohorts of the lARC study. These compared 11 cases of soft-tissue sarcoma and 32 cases of non-Hodgkin lymphoma with 55 and 158 controls, respectively (Kogevinas et al., 1995). Exposure to chlorophenols, phenoxy acid herbicides, dibenzodioxins and -furans and other agents was assessed by a team of industrial hygienists (Kauppinen et al., 1994). Odds ratios for non-Hodgkin lymphoma, not adjusted for exposure to other agents, were 1.3 (95% CI, 0.5-3.1) for any chlorophenol, 2.8 (0.5-17.0) for pentachlorophenol and 1.0 (0.3-3.1) for 2,4-dichlorophenol. No excess risk was found in relation to other chlorophenols, but the munber of exposed cases was small. The odds... 

As described in an earlier monograph (lARC, 1986), a case-control study in Sweden found a significant association between nasal and nasopharyngeal cancer and exposure to chlorophenols, independent of exposure to wood dust (Hardell et al., 1982). The same group of researchers also reported positive associations with high-grade exposure to chlorophenols in case-control studies of colon cancer (odds ratio, 1.8 95% CI, 0.6-5.3) and primary liver cancer (odds ratio, 2.2 95% CI, 0.7-7.3) (Hardell, 1981 Hardell et al., 1984). 

In a case-control study in the north of Sweden, Hallquist et al. (1993) compared 188 men and women aged 20-70 years who had thyroid cancer with age- and sex-matched controls (two per case) selected from a register of the local population. The cases were identified retrospectively from a cancer registry and excluded a proportion of patients (19%) who had died by the time of the study. Exposure to potential risk factors, including chlorophenols, was ascertained by postal questionnaire with a supplementary telephone interview if answers were incomplete. The response rates for the cases and controls were 95% and 90%, respectively. Of the 171 cases analysed, 107 had papillary tumours. Four cases and three controls reported exposure to chlorophenols (odds ratio, 2.8 95% CI, 0.5-18). [The Working Group noted that the method of statistical analysis was not the most appropriate for individually matched data, but this is unlikely to have produced serious bias.]... 

As part of a nested case-control study that is described more fully in the monograph on phenol (see this volume), Kauppinen et al. (1993) assessed exposure to chlorophenols in 136 men with respiratory cancer and 408 matched controls from a cohort of Finnish woodworkers. Nine cases were classified as exposed (odds ratio, 0.9 90% Cl, 0.4-1.8), and, after adjustment for smoking habits (when known), the risk estimate was little changed. 

In another nested case-control study based on the same cohort, Partanen et al. (1993) compared exposure to chlorophenols and other suspected risk factors in four cases of Hodgkin s disease, eight cases of non-Hodgkin lymphoma, 12 cases of leukaemia and 152 matched referents. Exposures were reconstructed through plant- and period-specific job-exposure matrices. Two of the cases were classed as exposed to chlorophenols (odds ratio, 0.9 95% Cl, 0.2-4.5). 

These investigations have shown significant associations with several types of cancer, but the most consistent findings have been for soft-tissue sarcoma and non-Hodgkin lymphoma. Although the odds ratios in some case-control studies may have been inflated by recall bias, this cannot explain all of the findings. Nor are they likely to have arisen by chance. It is not possible, however, to exclude a confounding effect of polychlorinated dibenzo-para-dioxins which occur as contaminants in chlorophenols. 

Harden, L. Sandstrom, A. (1979) Case-control study soft-tissue sarcomas and exposure to phenoxyacetic acids or chlorophenols. Br. J. Cancer, 39, 711-717... 

Pearce, N.E., Smith, A.J., Howard, J.K., Sheppard, R.A., Giles, H.J. Teague, C.A. (1986) Non-Hodgkin s lymphoma and exposure to phenoxyherbicides, chlorophenols, fencing work, and meat works employment a case-control study. Br. J. ind. Med., 43, 75-83... 

Case-control studies have been designed to determine if 2,3,7,8-TCDD exposure results in increased risks for site-specific cancers. Case-control studies have found significant increases in the risk of soft-tissue sarcomas in Swedish agricultural, forestry, and horticultural workers (Eriksson et al. 1981, 1990 Hardell and Eriksson 1988 Hardell and Sandstrom 1979), workers involved in manufacturing and application of phenoxy herbicides (Kogevinas et al. 1995), and New Zealand farmers (Smith et al. 1984a). In the Eriksson et al. (1990) study, the risk ratio of soft-tissue sarcoma was 1.80 (95% 0=1.02-3.18) in subjects exposed to phenoxyacetic acid herbicides and/or chlorophenols. In subjects exposed to phenoxyacetic acid herbicides only or chlorophenols only, the risk ratios were 1.34 (95% 0=0.7-2.56) and 5.25 (95%... 

On the other hand, Hardell and Sandstrom (32) and Eriksson et al. (34) conducted two case-control studies in Sweden and reported an increased risk of soft-tissue sarcomas (cancers of soft-tissue) in men who were exposed to trichlorophenol or to phenoxy herbicides. In a third case-control study, investigators suggested that phenoxy herbicides and chlorophenols may also predispose to Hodgkin s lymphoma. Other sources however, provide little support for this theory (35). 

Several studies have assessed the plausibility of the association between soft tissue sarcomas and exposure to phenoxy herbicides and chlorophenols. Table VI lists two case-control studies conducted in Sweden, which selected controls from the general population and concluded that exposure to the herbicides or to chlorophenols resulted in a greater than 5-fold excess in soft tissue sarcomas (38-39). A New Zealand study found no association with exposure to phenoxy herbicides (40). This study drew controls from other cancer cases in the National Cancer Registry of New Zealand. However, in the New Zealand study, a 5-fold excess of STS was noted in persons who handled animal pelts, which are sometimes preserved with trichlorophenols containing isomers of dioxin. 

Harden L and Sandstrom A Case-control study soft tissue sarcoma and exposure to phenoxyacetic acids or chlorophenols. 

The carcinogenicity of 2,3,7,8-TCDD in humans has been assessed in numerous case-control and mortality cohort studies of chemical manufacturing and processing workers and phenoxy herbicide and chlorophenols applicators, Vietnam veterans exposed to Agent Orange, and residents of Seveso, Italy. A major weakness in many of these studies is the lack of adequate exposure data. Exposure levels or... 

The chlorophenoxyalkanoic acids constitute yet another economically important group of halogenated aromatic hydrocarbons. They are widely used as herbicides to control dicotyledonous weeds. The most important of them are 2,4-D and its propionic and butyric acid homologs, 4-chloro> 2-methylphenoxyacetic acid (MCPA), and 2,4,5>trichlorophenoxyacetic add (2,4,5-T). In all the cases studied, aerobic biodegradation proceeds by removal of the aliphatic side chain with the formation of the corresponding chlorinated phenoL Thus, formation of 2,4 chlorophenol from both 2,4-D and 4-(2,4-dichlorophenoxy)-butyric acid, 4-chloro-o-cresol from MCPA, and 2,4,5-trichlorophenol from 2,4,5-T has been... 

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