Occupational Exposure to Endocrine-Disrupting Pesticides and the Potential for Developing Hormonal Cancers.

Abstract

It is suspected that endocrine-disrupting pesticides are involved in the development of several cancer and noncancer health risks in humans and wildlife. A large number of pesticides show endocrine-disrupting activities. The potential for human and animal exposure to such pesticides is very high. Farmers, as a group, may be particularly at risk, because they are subject to higher-than-average levels of exposure to pesticides over longer-than-average periods. Recent studies have shown that the incidence of hormone-related organ cancers, or hormonal cancers, is elevated among farmers. Exposure to endocrine-disrupting pesticides, particularly to DDT and phenoxy herbicides, is suspected of involvement in some of these hormonal cancers. There is a clear need for a refined epidemiological study that focuses on specific pesticides, accurately assesses exposure, and then examines any association between pesticides and hormonal cancers among farmers.

Introduction

Endocrine disrupters are defined as exogenous chemical agents that interfere with the synthesis, secretion, transport, binding, action, or elimination of natural hormones (U.S. Environmental Protection Agency [U.S. EPA], 1997). Several herbicides and insecticides have been reported to have endocrine-disrupting properties (Colborn, Vom Saal, & Soto, 1993).

Exposure to environmental endocrine-disrupting chemicals has been associated with

* abnormal thyroid function in birds (Moccia, Fox, & Britton, 1986) and fish (Moccia, Leatherland, & Sonstegard, 1981);

* decreased fertility in birds (Shugart, 1980), fish (Leatherland, 1992), shellfish (Gibbs, Pascoe, & Burt, 1988), and mammals (Reijnders, 1986);

* decreased hatching success in fish (Mac, Schwartz, & Edsall, 1988), birds (Kubiak et al., 1989), and turtles (Bishop, Brooks, Carey, Norstrom, & Lean, 1991);

* demasculinization of male fish (Munkittrick, Port, Van der Krakk, Smith, & Rokosh, 1991), birds (Fry & Toone, 1981), and mammals (Beland, 1989);

* defeminization and masculinization of female fish (Davis & Bortone, 1992), gastropods (Ellis & Pattisina, 1990), and birds (Fry & Toone, 1981); and

* alteration of immune function in birds (Erdman, 1988) and mammals (Martineau et al., 1988).

Tributyltin (TBT) compounds have caused the disappearance or reduction of the dogwhelk snail along the British coast (Bryan, Gibbs, & Burt, 1988). Bright and Ellis (1990) found that marine snails in the Northeast Pacific had signs of imposex (a condition in which females develop part of the male reproductive system, including a penis and a vas deferens) caused by TBT pollution. Fish near sewage treatment plants in the United Kingdom developed hermaphroditic characteristics, thought to be caused by the widespread use of contraceptive pills and the subsequent release of ethynylestradiol (via sewage treatment plants) (Purdom et al., 1994). Howell, Black, and Bortone (1980) found that female mosquito fish downstream from pulp and paper mills in Florida were masculinized and developed the male sex organ. Male alligators from Lake Apopka, Florida, became demasculinized after a mixture of dicofol, DDT, and DDE spilled into that lake in 1980 (Guillete et al., 1994). Eggs of Forster's terns from Green Bay, Wisconsin, had higher residues of TCDD and PCBs than those of Foster's terns from Lake Poygan and showed lower hatching successes (Kubiak et al., 1989). Eroschenko (1981) reported that kepone decreased follicular development, induced ovarian regression, and inhibited ovulation and egg-laying in adult quails. Reijnders (1986) found that PCBs were the likely cause of reproductive failure found in the western Wadden Sea seals. The decrease in numbers of beluga whales in the St. Lawrence estuary, Quebec, Canada, is considered to be the result of environmental contaminants, such as PCBs, dieldrin, and 2,3,7,8-TCDD (De Guise, Martineau, Beland, & Fournier, 1995).

Some of the endocrine-disrupting pesticides, strongly resistant to biodegradation, are present in the food chain and accumulate in human bodies (Colborn & Clement, 1992). These chemicals can bind to intracellular receptor proteins for steroid hormones (Korach, Sarver, Chae, McLachlan, & McKinney, 1987) and evoke hormonal effects in humans (Guzelian, 1982), animals (Gray et al., 1989), and cell culture (Soto, Justicia, Wray, & Sonnenschein, 1991; Soto, Lin, Justicia, Silvia, & Sonnenschein, 1992). As indicated in Table 1, some of these pesticides have shown estrogenic properties, including toxaphene, DDT, endosulfan, 1-hydroxychlordene, dicofol, heptachlor, dieldrin, chlordecone, and [beta]-HCH (Roy et al., 1997; Soto, Chung, & Sonnenschein, 1994; Soto et al., 1995; Davis et al,, 1993). Workers exposed to chlordecone have been found to have oligospermia and sterility (Cohn et al., 1978). U.S. EPA (1997) reported that PCBs may be involved in the induction of endometriosis.

The residues of DDT and other organochlorine pesticides have been found in human breast milk and adipose tissue (Dewailly et al., 1994; Falck, Ricci, Wolff, Godbold, & Deckers, 1992; Krieger et al., 1994; Mussalo-Rauhamaa, Hasanen, Pyysalo, Kauppila, & Pantzar, 1990; Unger, Kiar, Blichert-Toft, Olsen, & Clausen, 1984; Wassermann et al., 1976; Wolff, Toniolo, Lee, Rivera, & Dubin, 1993). Exposure to these pesticides has been implicated in breast cancer risk (Davis et al., 1993; Soto & Sonnenschein, 1985; Wolff & Toniolo, 1995). There is also a concern that estrogen-like chemicals may be involved in the development of testicular and prostate cancers (Giwercman, Carlsen, Keiding, & Skakkebaek, 1993; Santti, Newbold, Makela, Pylkknen, & McLachlan, 1994). Environmental estrogens are suspect in the lower sperm counts found in the Western world. A significant decrease in male sperm counts coincides with increased use of estrogenic chemicals during the past 50 years (Sharpe & Skakkebaek, 1993).

Thus, the widespread presence of environmental estrogens and the possibility that their degradation products will persist in the environment, coupled with the potential for inadvertent exposure of humans and wildlife to endocrine-disrupting pesticides, raise significant safety issues. Although most of the pesticides show weak endocrine-disrupting activity, that low potency does not rule out the possibility of toxicity resulting from chronic exposure in animals or humans.

As an occupational group, farmers receive higher-than-average exposure to pesticides. In particular, farm managers, who tend to live on the farm, are likely to have longer-term exposures to pesticides and exposures at higher levels than those received by other farm workers and the general population. A study from the Wenatchee area in eastern Washington state, based on dust sampling, revealed that houses located on farms had higher levels of pesticides than houses located in nearby urban settings (Simcox, Fenske, Wolz, Lee, & Kalman, 1995). Most farms are family owned and passed down from generation to generation; thus, it is reasonable to assume that farmers' children are born and raised on the farm. Children are likely to be exposed to pesticides even if they are not involved in farm activities. A major concern is that exposure to endocrine-disrupting pesticides during critical periods in development may have profound and irreversible effects on the future well-being of wildlife and humans, Chronic exposur e to endocrine-disrupting pesticides after maturity may also present a health risk.

In the section that follows, this paper discusses some experimental models in which susceptibility to hormonal cancers was found in response to exposure to endocrine-disrupting pesticides. Subsequent sections report on epidemiological studies of hormone-related organ cancers in farmers who are thought to be exposed to high levels of pesticides.

Endocrine-Disrupting Pesticides and Hormonal Cancers in Experimental Models

Several endocrine-disrupting pesticides are involved in the induction or promotion of endocrine cancers, or both. Recently, exposure of Sprague-Dawley female rats to o,p'-DDT has been shown to increase epithelial cell proliferation and differentiation of abdominal mammary glands (Brown & Lamartiniere, 1995). It has been reported that p,p'-DDT promotes mammary-gland tumors in male Sprague-Dawley rats (Scribner & Mottet, 1981). Atrazine has been found to induce mammary gland tumors in Sprague-Dawley female rats (Wetzel et al., 1994; Stevens et al., 1994). Dunnick, Elwell, Huff, and Barrett (1995) reported that 1,2-dibromoethane, 1,2-dicloroethane, glycidol, and sulfallate caused mammary-gland neoplasms in both male and female rats and mice. Huff, Cirvello, Haseman, and Bucher (1991) found that dichlorvos caused mammary-gland neoplasms in female mice. TCDD has been found to increase the incidence of liver, bile-duct, skin, lung, palate, tongue, stomach, and thyroid-gland cancer in rodents (Kimbrough et al., 197 8; Kociba, 1984; Kociba et al., 1978; National Toxicology Program, 1980; National Toxicology Program, 1982; Rao, Subbarao, Prasad, & Scarpelli, 1988; Van Miller, Lalich, & Allen, 1977). Rats and mice that were exposed to amitrole developed thyroid and liver tumors (Council on Scientific Affairs, 1988). Hexachlorobenzene induced thyroid and liver neoplasms in hamsters and liver tumors in mice and female rats (Council on Scientific Affairs, 1988). Toxaphene increased the incidence of liver cancers in mice and thyroid tumors in rats (Council on Scientific Affairs, 1988). Liver tumor, which is not a hormone-related organ cancer, is the primary target for other pesticides, including kepone, methoxychlor, lindane, heptachlor, mirex, aldrin, and, dieldrin (Agency for Toxic Substances and Disease Registry, 1994; International Agency for Research on Cancer [IARC], 1987; IARC, 1991; International Programme on Chemical Safety [IPCS], 1984a; IPCS, 1984b).

Endocrine-Disrupting Pesticides and Hormonal Cancers in Humans

Several epidemiological studies have shown that cancer risks among farmers are elevated compared with those among the general population (Blair, Malker, Cantor, Burmeister, & Wiklund, 1985; Blair & Zahm, 1991; Pearce & Reif, 1990). Pesticides are the agents most suspected in this trend, but there is a lack of data that would show any individual agricultural chemical involved in the development of cancers among farmers; existing studies of farmers do not provide specific assessment of pesticide exposure. Most of the studies that show an association between pesticide exposure and cancer have been conducted among pesticide applicators or workers in pesticide-manufacturing plants.

Hormonal Cancers in Farmers

Findings from studies that address hormonal cancers in farmers are summarized in Table 2 Most retrospective follow-up studies of mortality from prostate cancer among farmers have not shown an association between farming and death by prostate cancer (Morrison et al., 1993; Stark, Chang, Fitzgerald, Riccardi, & Stone, 1987). One study did demonstrate an association between farmers and death by prostate cancer; however, the finding was not statistically significant (Howe & Lindsay, 1983). In the retrospective follow-up studies that looked at farmers and the incidence of prostate cancer, no association was found (Kristensen, Andersen, Irgens, Laake, & Bye, 1996; Wiklund & Holm, 1986). Studies based on the case-control approach, however, reported an association between farmers and prostate cancer (Brownson, Reif, Chang, & Davis, 1989; Burmeister, Everett, Van Lier, & Isacson, 1983; Checkoway, DiFerdinando, Hulka, & Mickey, 1987; Fincham, Hanson, & Berkel, 1992; Keller & Howe, 1994; Le Marchand, Kolonel, & Yoshizawa, 1991; Pearce, Sheppard, & Fraser, 1987a; Reif, Pearce, & Fraser, 1989; Van der Gulden, Kolk, & Verbeek, 1992; Van der Gulden, Kolk, & Verbeek, 1995). All of the proportional-mortality-ratio (PMR) studies showed an association between farmers and prostate cancer (Blair, Dosemici, & Heineman, 1993; Burmeister, 1981; Delzell & Grufferman, 1985; Gallagher et al., 1984a; Gallagher, Threlfall, Spinelli, & Band, 1984b; Saftlas, Blair, Cantor, Hanrahan, & Anderson, 1987; Stubbs, Harris, & Spear, 19 84; Une, Schuman, Caldwell, & Whitlock, 1987). Davis, Blair, & Hoel (1992) conducted a meta-analysis of prostate cancer among farmers by using data from 21 broad occupational surveys assembled from eight industrialized countries. They found that combined relative risk (cRR) was 1.08 (95% confidence interval [CI] 1.06-1.11). Most studies of the association between farmers and prostate cancer risk have not provided assessments of the exposure risk factors associated with farming.

Two retrospective follow-up studies of farming and the development of testicular-cancer showed a nonsignificant association (Kristensen et al., 1996; Wiklund, Dich, & Holm, 1986). Several case-control studies also showed an association between farmers and testicular cancer (Graham & Gibson, 1972; Hayes et al., 1990; McDowall & Balarajan, 1984; Mills, Newell, & Johnson, 1984; Swerdlow, Douglas, Huttly, & Smith, 1991; Van den Ededn, Weiss, Strader, & Daling, 1991). Only one study, however, showed a significant association (Mills et al.). One PMR study of farmers and testicular cancer showed a nonsignificant association among nonwhite farmers (Blair et al., 1993). Another study showed no association at all between farming and testicular cancer (Saftlas et al., 1987). A meta-analysis of testicular cancer from eight industrialized countries showed that the cRR of testicular cancer among farmers was 0.88 (95% CI: 0.794-1.03) (Davis et al., 1992).

A retrospective follow-up study of farmers and ovarian cancer death in Canada showed a significant association between farming and ovarian cancer (Aronson & Howe, 1994). Another retrospective follow-up study, in Norway, did not show any association (Kristensen et al,, 1996). A prospective follow-up study of farming and ovarian cancer incidence in Iowa also did not show any association (Folsom et al., 1996). Thus, findings about an association between farming and ovarian cancer are inconsistent.

Three studies--one retrospective follow-up, one-prospective follow-up, and one PMR study--showed an association between farmers and endometrial cancer. In none of these studies, however, were the results statistically significant (Blair et al., 1993; Folsom et al., 1996; Kristensen et al., 1996).

A retrospective follow-up study of Norwegian women engaged in agriculture showed a nonsignificant association with breast cancer development (Kristensen et al., 1996). A PMR study in the United States also showed a nonsignificant association between breast cancer among nonwhite male farmers (Blair et al., 1993). A meta-analysis of data from eight industrialized countries showed a weak association between breast cancer and farming (Davis et al., 1992).

A Norwegian retrospective follow-up study of farming showed a nonsignificant association between thyroid cancer development and farming in both male and female groups (Kristensen et al., 1996). A PMR study conducted in the United States showed a nonsignificant association between thyroid cancer death and nonwhite female farmers and white male farmers (Blair et al., 1993). Neither of these studies addressed specific exposure among farmers that might have been involved with thyroid cancer.

In conclusion, farmers show a higher incidence of some hormonal cancers. Unfortunately, many kinds of exposure are involved in farming, making it difficult to find out which exposure is associated with cancer.

Hormonal Cancers Among Licensed Pesticide Applicators

Licensed pesticide applicators are likely to have significantly high exposure to pesticides; for that reason, this paper reviews separately the incidence rates of hormonal cancers in this population. Findings from studies related to hormonal cancers among licensed applicators are summarized in Table 3.

A retrospective follow-up study of Canadian farmers showed no association between acres of insecticides sprayed and prostate cancer; the study did show an association between acres of herbicides sprayed and prostate cancer, but the association was not statistically significant. A significant association was observed among farmers 45 to 69 years of age who sprayed herbicides on more than 250 acres (Morrison et al., 1993). Out of several studies of licensed pesticide applicators (Wiklund, Dich, Holm, & Eklund, 1989; Blair, Grauman, Lubin, & Fraumeni, 1983; Cantor & Booze, 1991), only one showed an association between prostate cancer and the occupation of pesticide applicator; the association was not statistically significant (Cantor and Booze, 1991).

Several case-control studies have studied the association between exposure to pesticides of different types and prostate cancer. For general pesticide exposure, three studies showed a nonsignificant association with prostate cancer (Checkoway et al., 1987; Le Marchand et al., 1991; Van der Gulden et al., 1995); one study showed no association (Ewings & Bowie, 1996). For insecticide exposure, there was no association with prostate cancer (Fincham et al., 1992). For herbicide exposure, there was an association with prostate cancer (Checkoway et al., 1987). A PMR study of herbicide and insecticide exposure among Wisconsin farmers showed a nonsignificant association with prostate cancer. There was, however, no trend in association from low to high levels of agricultural production (Saftlas et al., 1987).

Two retrospective follow-up studies of Swedish licensed pesticide applicators showed a nonsignificant association with testicular cancer (Dich, Wiklund, & Holm, 1996; Wiklund, Dich, & Holm, 1986). Two case-control studies showed a nonsignificant association between pesticide exposure and testicular cancer (Hayes et al., 1990; Swerdlow et al., 1991). One study showed a nonsignificant association between herbicide exposure and testicular cancer (Swerdlow et al.).

A case-control study in Italy showed a significant association between herbicide exposure and ovarian cancer; the association was especially observed among women younger than 55 years of age (Donna et al., 1984).

Exposure to Individual Endocrine-Disrupting Pesticides

Prostate, testicular, ovarian, breast, and thyroid cancers have been found to be associated with endocrine-disrupting pesticides. The main endocrine-disrupting pesticides in these studies were DDT and phenoxy herbicides (e.g., 2,4-D). Several studies have looked at levels of p,p'-DDE in breast tissue or the serum of breast-cancer patients (Dewailly et al., 1994; Falck et al., 1992; Krieger et al., 1994; MussaloRauhamaa et al., 1990; Unger et al., 1984; Wassermann et al., 1976; Wolff et al., 1993) (Table 4). Only two of these studies showed a significant association between p,p'-DDE in breast tissue or serum and breast cancer (Falck et al,, Wolff et al.). An analysis of all these studies together demonstrated a weak association between p,p'-DDE in breast tissue or serum and breast cancer (Adami et al., 1995).

Findings from studies that addressed individual endocrine-disrupting pesticides and other hormonal cancers are summarized in Table 5. Two retrospective follow-up studies of workers exposed to phenoxy herbicides showed a nonsignificant association with prostate cancer (Bond et al., 1988; Coggon, Pannett, Winter, Acheson, & Bonsall, 1986). Another study showed no association between exposure to phenoxy herbicides and prostate cancer (Lynge, 1985). A prospective follow-up study in Finland showed an association with prostate cancer for men who sprayed 2,4-D and 2,4,5-T (Riihimaki, Asp, & Hernberg, 1982). Two retrospective follow-up studies showed a nonsignificant association between exposure to phenoxy herbicides and testicular cancer (Bond et al.; Coggon et al.). A retrospective follow-up study in Denmark showed a slight association between exposure to phenoxy herbicides and ovarian cancer (Lynge). One retrospective study showed a nonsignificant association between exposure to phenoxy herbicides and breast cancer (Saracci et al., 1991). Two retrospective follow-up studies showed no association between exposure to phenoxy herbicides and breast cancer (Lynge; Kogevinas et al., 1993). A retrospective follow-up study of workers exposed to phenoxy herbicides showed a nonsignificant association with thyroid cancer (Saracci et al.). A case-control study in Italy showed a nonsignificant association between exposure to triazine and ovarian cancer (Donna et al., 1989). By contrast, an ecological study of triazine exposure in Kentucky counties revealed a statistically significant increase in breast cancer risk with triazine exposure (Kettles, Browning, Prince, & Horstman, 1997).

Conclusions

From the findings discussed above, it is difficult to draw a conclusion about whether exposure to endocrine-disrupting pesticides is associated with the development of hormone-related organ cancers; the epidemiological studies fail to provide detailed assessments of pesticide exposures. The results of both experimental models and human studies indicate a strong need for a refined epidemiological study focusing on specific pesticides with accurate exposure assessment, followed by an examination of the association between pesticide exposure and hormonal cancers among farmers. Recently, the authors evaluated the potential for genomic instability to occur as a result of occupational and environmental exposure to endocrine-disrupting chemicals. It has been shown that several structural, numerical, and functional changes occur in the genome at cellular levels in response to synthetic-stilbene-estrogen exposure (Roy et al., 1997). Some other phenolic estrogen-like occupational chemicals, such as bisphenol A, phenyip henol, and nonyiphenol, are also linked to some of the effects that have been observed to occur in response to stilbene estrogen. These compounds also alter cell cycle kinetics, induce DNA damage, produce telomeric associations, and trigger chromosomal aberrations. Whether weak or strong, the endocrine-disrupting stress of a chemical, if not overcome, will add extra hormonal burden to the system; moreover, those endocrine-disrupting environmental and industrial chemicals capable of producing genomic instability will induce the additional burden of that instability. Although some of these compounds may have only weak endocrinedisrupting activities, they may have different activities in the generation of genomic instability. For example, nonylphenol is weak in estrogen-like action compared with stilbene estrogen; however, it is equal to or more potent than stilbene estrogen in producing telomeric associations in MCF7 cells. The additive or synergistic extra burden of estrogenicity and genomic instability could produce more detrimental effects than estrogenic action alone. Biological monitoring of endocrine-disrupting pesticides and determination of their ability to produce genomic instability in the target organ should lead to a better understanding of how exposure to these chemicals may influence health effects in humans and wildlife.

Corresponding Author: Deodutta Roy, Ph.D., Department of Environmental Health Sciences, 1667 University Blvd., Ryals Building #309E, University of Alabama, Birmingham, AL 35294-0022. E-mail: [less than][e-mail][greater than].

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TABLE 1

Some Endocrine-Disrupting and Estrogen-like Pesticides


              Endocrine-Disrupting Pesticides

Herbicides    2,4,5-T
              2,4-D
              Alachlor
              Amitrole
              Atrazine
              Metribuzin
              Nitrofen
              Trifluralin

Insecticides  [beta]-Hexachlorocyclohexane
              ([beta]-HCH)
              Carbaryl
              Chlordane
              Dicofol
              Dieldrin
              DDT and its metabolites
              Endosulfan
              Heptachlor and H-epoxide
              Lindane
              Methomyl
              Methoxychlor
              Mirex
              Oxychlordane
              Parathion
              Synthetic pyrethroid
              Toxaphene



              Estrogen-like Pesticides

Herbicides    2,4,5-T








Insecticides  [beta]-HCH

              Kepone (chlordecone)
              I-Hydroxychlordene
              Dicofol
              Dieldrin
              p.p'-DDT
              o,p'-DDT
              o,p'-DDE
              p.p'-DDE
              DDT
              DDE
              Endosulfan
              Heptachlor
              Methoxychlor
              Toxaphene
TABLE 2

Hormonal Cancers and Farming Occupation


Study Groups                      Place of Study     Cancer Site

Retrospective follow-up study
Farmers                           Canada             Prostate
Farmers                           Norway             Prostate
Men engaged in agriculture        Norway             Prostate
Agricultural occupation           Norway             Testis
Farmers                           Norway             Testis
Agricultural occupation           Norway             Ovary
Women engaged in agriculture      Norway             Endometrium
Female farmers                    Norway             Endometrium
Women engaged in agriculture      Norway             Breast
Female farmers                    Norway             Breast
Men engaged in agriculture        Norway             Breast
Women engaged in agriculture      Norway             Thyroid
Female farmers                    Norway             Thyroid
Men engaged in agriculture        Norway             Thyroid
Male farmers                      Norway             Thyroid
Agricultural workers              Sweden             Prostate
   1961-1966
   1967-1973
   1974-1979
Farmers or farm workers           Canada             Prostate
Persons in agricultural industry  Canada             Prostate
Farm owners or farm operators     New York State     Prostate
Agricultural workers              Sweden             Testis
   1961-1966
   1967-1973
   1974-1979
Agricultural industry             Canada             Ovary

Prospective follow-up study
Farm women                        Iowa               Ovary
Farm women                        Iowa               Endometrium

Case-control study
Farmers & farmworkers             England            Prostate
Farmers                           Netherlands        Prostate
   Between 1958 and 1968
   Longest-held occupation
Farmers and farm owners           Netherlands        Prostate
   Between 1960 and 1970
   Longest-held jobs
Farm workers                      Netherlands        Prostate
   Between 1960 and 1970
   Longest-held jobs
Farmers                           Canada             Prostate
Farmers                           New Zealand        Prostate
   Age 20-59
   Age [greater than] 60
   Orchard & crop farmers
Farmers                           New Zealand        Testis
   Age 20-59
   Age [greater than] 60
Farmers & farm managers           New Zealand        Prostate
Agricultural workers              New Zealand        Prostate
Farmers & farm managers           Hawaii             Prostate
Farmers                           Iowa               Prostate
Farming occupation                Illinois           Prostate
Farmers                           Missouri           Prostate
Farmers                           Missouri           Testis
Farming industries                North Carolina     Prostate

Farming occupation                England and Wales  Testis
Farmers                           England and Wales  Testis
Farmers & farm managers           New Zealand        Testis
Agricultural workers              New Zealand        Testis
Farmers                           England            Testis
   Seminoma
   Teratoma
   All
Farmers, foresters & fishermen    England            Testis



Study Groups                      Measurement

Retrospective follow-up study
Farmers                           SMR
Farmers                           SIR
Men engaged in agriculture        SIR
Agricultural occupation           SIR
Farmers                           SIR
Agricultural occupation           SIR
Women engaged in agriculture      SIR
Female farmers                    SIR
Women engaged in agriculture      SIR
Female farmers                    SIR
Men engaged in agriculture        SIR
Women engaged in agriculture      SIR
Female farmers                    SIR
Men engaged in agriculture        SIR
Male farmers                      SIR
Agricultural workers              RR
   1961-1966
   1967-1973
   1974-1979
Farmers or farm workers           SMR
Persons in agricultural industry  SMR
Farm owners or farm operators     SMR
Agricultural workers              RR
   1961-1966
   1967-1973
   1974-1979
Agricultural industry             SMR

Prospective follow-up study
Farm women                        RR
Farm women                        RR

Case-control study

Farmers & farmworkers             OR
Farmers                           OR
   Between 1958 and 1968
   Longest-held occupation
Farmers and farm owners           OR
   Between 1960 and 1970
   Longest-held jobs
Farm workers                      OR
   Between 1960 and 1970
   Longest-held jobs
Farmers                           OR
Farmers                           OR
   Age 20-59
   Age [greater than] 60
   Orchard & crop farmers
Farmers                           OR
   Age 20-59
   Age [greater than] 60
Farmers & farm managers           OR
Agricultural workers              OR
Farmers & farm managers           OR
Farmers                           OR
Farming occupation                OR
Farmers                           OR
Farmers                           OR
Farming industries                %

Farming occupation                OR
Farmers                           OR
Farmers & farm managers           OR
Agricultural workers              OR
Farmers                           OR
   Seminoma
   Teratoma
   All
Farmers, foresters & fishermen    OR



Study Groups                      Results

Retrospective follow-up study
Farmers                           0.92 (95% CI: 0.87-0.98)
Farmers                           90 (95% CI: 75-107)
Men engaged in agriculture        96 (95% CI: 85-108)
Agricultural occupation           107 (95% CI: 90-125)
Farmers                           109 (95% CI: 87-134)
Agricultural occupation           92 (95% CI: 78-107)
Women engaged in agriculture      108 (95% CI: 92-125)
Female farmers                    118 (95% CI: 90-151)
Women engaged in agriculture      105 (95% CI: 96-113)
Female farmers                    84 (95% CI: 72-99)
Men engaged in agriculture        65 (95% CI: 18-151)
Women engaged in agriculture      118 (95% CI: 91-151)
Female farmers                    116 (95% CI: 69-181)
Men engaged in agriculture        116 (95% CI: 86-152)
Male farmers                      124 (95% CI: 83-177)
Agricultural workers
   1961-1966                      0.9
   1967-1973                      0.93
   1974-1979                      1.01
Farmers or farm workers           1.16 (p [greater than] .05)
Persons in agricultural industry  1.36 (p [greater than] .05)
Farm owners or farm operators     92.1
Agricultural workers
   1961-1966                      0.83 (95% CI: 0.59-1.18)
   1967-1973                      0.94 (95% CI: 0.67-1.32)
   1974-1979                      1.35 (95% CI: 0.94-1.93)
Agricultural industry             1120 (95% CI: 136-4047)

Prospective follow-up study
Farm women                        0.90 (95% CI: 0.50-1.62)
Farm women                        1.25 (95% Cl: 0.89-1.75)

Case-control study
Farmers & farmworkers             0.74 (95% CI: 0.46-1.18)
Farmers
   Between 1958 and 1968          1.49 (95% CI: 0.68-3.28)
   Longest-held occupation        1.53 (95% CI: 0.72-3.26)
Farmers and farm owners
   Between 1960 and 1970          0.76 (95% CI: 0.49-1.19)
   Longest-held jobs              0.78 (95% CI: 0.51-1.18)
Farm workers
   Between 1960 and 1970          7.82 (95% CI: 2.09-29.29)
   Longest-held jobs              2.74 (95% CI: 0.94-7.98)
Farmers                           1.31 (95% CI: 1.11-1.55)
Farmers
   Age 20-59                      1.41 (95% CI: 0.91-2.19)
   Age [greater than] 60          1.25 (95% CI: 1.12-1.40)
   Orchard & crop farmers         1.12 (95% CI: 0.80-1.57)
Farmers
   Age 20-59                      0.61 (95% CI: 0.41-0.92)
   Age [greater than] 60          0
Farmers & farm managers           1.14 (90% CI: 0.90-1.46)
Agricultural workers              0.97 (90% CI: 0.56-1.68)
Farmers & farm managers           1.2 (95% CI: 0.7-2.0)
Farmers                           1.19 (p [less than]0.05)
Farming occupation                1.15 (95% CI: 0.99-1.35)
Farmers                           1.33 (95% CI: 1.18-1.51)
Farmers                           0.82 (95% CI: 0.39-1.67)
Farming industries                75% of cases in farming,
                                  37.5% of controlin farming
Farming occupation                1.57 (95% CI: 0.94-2.64)
Farmers                           1.89 (95% CI: 0.99-3.60)
Farmers & farm managers           0.98 (95% CI: 0.57-1.68)
Agricultural workers              0.53 (95% CI: 0.21-1.37)
Farmers
   Seminoma                       1.06
   Teratoma                       1.35
   All                            1.05
Farmers, foresters & fishermen    1.09 (95% CI: 0.65-1.83)



Study Groups                      Authors

Retrospective follow-up study
Farmers                           Morrison et al. (1993)
Farmers                           Kristensen et al. (1996)
Men engaged in agriculture        Kristensen et al. (1996)
Agricultural occupation           Kristensen et al. (1996)
Farmers                           Kristensen et al. (1996)
Agricultural occupation           Kristensen et al. (1996)
Women engaged in agriculture      Kristensen et al. (1996)
Female farmers                    Kristensen et al. (1996)
Women engaged in agriculture      Kristensen et al. (1996)
Female farmers                    Kristensen et al. (1996)
Men engaged in agriculture        Kristensen et al. (1996)
Women engaged in agriculture      Krissensen et al. (1996)
Female farmers                    Kristensen et al. (1996)
Men engaged in agriculture        Kristensen et al. (1996)
Male farmers                      Kristensen et al. (1996)
Agricultural workers              Wiklund & Holm (1986)
   1961-1966
   1967-1973
   1974-1979
Farmers or farm workers           Howe & Lindsay (1983)
Persons in agricultural industry  Howe & Lindsay (1983)
Farm owners or farm operators     Stark et al. (1987)
Agricultural workers              Wiklund et al. (1986)
   1961-1966
   1967-1973
   1974-1979
Agricultural industry             Aronson & Howe (1994)

Prospective follow-up study
Farm women                        Folsom et al. (1996)
Farm women                        Folsom et al. (1996)

Case-control study
Farmers & farmworkers             Ewings and Bowie (1996)
Farmers                           van der Gulden et al. (1992)
   Between 1958 and 1968
   Longest-held occupation
Farmers and farm owners           van der Gulden et al. (1995)
   Between 1960 and 1970
   Longest-held jobs
Farm workers                      van der Gulden et al. (1995)
   Between 1960 and 1970
   Longest-held jobs
Farmers                           Fincham et al. (1992)
Farmers                           Reif et al. (1989)
   Age 20-59
   Age [greater than] 60
   Orchard & crop farmers
Farmers                           Reif et al. (1989)
   Age 20-59
   Age [greater than] 60
Farmers & farm managers           Pearce et al. (1987a)
Agricultural workers              Pearce et al. (1987a)
Farmers & farm managers           Le Marchand et al. (1991)
Farmers                           Burmeister et al. (1983)
Farming occupation                Keller & Howe (1994)
Farmers                           Brownson et al. (1989)
Farmers                           Brownson et al. (1989)
Farming industries                Checkoway et al. (1987)

Farming occupation                McDowall & Balarajan (1984)
Farmers                           McDowall & Balarajan (1984)
Farmers & farm managers           Pearce et al. (1987b)
Agricultural workers              Pearce et al. (1987b)
Farmers                           Swerdlow et al. (1991)
   Seminoma
   Teratoma
   All
Farmers, foresters & fishermen    Swerdlow et al. (1991)
Farming exposure                          England
Farmers                                   Denmark
Farming, foresty, gardening, & fishing    Denmark
Farming occupation                        Texas
Agricultural indusnries                   Texas
Farming                                   New Mexico
Farmers & farm managers                   Washington state
Farm workers                              Washington state
Agricultural, foresty, & fishery workers  Washington, DC
  All
  Seminoma
Germ cell tumors
Farming occupation                        New York
Farming employment                        Washington DC
  Current
  Ever
Farmers                                   Canada
Farm workers                              Canada
Farmers                                   23 states in US
  White
  Nonwhite
Farmers                                   23 states in US
  White
  Nonnwhite
Farmers                                   23 states in US
  White
  Nonwhite
Farmers                                   23 states in US
  White women
  Nonwhite women
  White men
  Nonnwhite men
Farmers                                   23 states in US
  White women
  Nonwhite women
  White men
  Nonwhite men
Farmers                                   Wisconsin
  All cohorts
  Born 1905--1958
Farmers                                   Wisconsin
  All cohorts
  Born 1905--1958
Farmers                                   North Carolina
  White
  Nonwhite
Farm workers                              California
  White
  Nonwhite
Farm owners & farm managers               California
  White
  Nonwhite
Farmers                                   Iowa

Farmers                                   South Carolina
  White
  Nonwhite

Meta-analysis
Farmers                                   8 industrialized countries
Farmers                                   8 industrialized countries
Female farmers                            8 industrialized countries



Farming exposure                          Testis       OR
Farmers                                   Testis       OR
Farming, foresty, gardening, & fishing    Testis       OR
Farming occupation                        Testis       OR
Agricultural indusnries                   Testis       OR
Farming                                   Testis       OR
Farmers & farm managers                   Testis       OR
Farm workers                              Testis       OR
Agricultural, foresty, & fishery workers  Testis       OR
  All
  Seminoma
Germ cell tumors
Farming occupation                        Testis       OR
Farming employment                        Testis       OR
  Current
  Ever
Farmers                                   Prostate     PMR
Farm workers                              Prostate     PMR
Farmers                                   Prostate     PMR
  White
  Nonwhite
Farmers                                   Testis       PMR
  White
  Nonnwhite
Farmers                                   Endometrium  PMR
  White
  Nonwhite
Farmers                                   Breast       PMR
  White women
  Nonwhite women
  White men
  Nonnwhite men
Farmers                                   Thyroid      PMR
  White women
  Nonwhite women
  White men
  Nonwhite men
Farmers                                   Prostate     PMR
  All cohorts
  Born 1905--1958
Farmers                                   Testis       PMR
  All cohorts
  Born 1905--1958
Farmers                                   Prostate     PMR
  White
  Nonwhite
Farm workers                              Prostate     PMR
  White
  Nonwhite
Farm owners & farm managers               Prostate     PMR
  White
  Nonwhite
Farmers                                   Prostate     PMR
                                                       SMR
Farmers                                   Prostate     PMR
  White
  Nonwhite

Meta-analysis
Farmers                                   Prostate     cRR
Farmers                                   Testis       cRR
Female farmers                            Breast       cRR



Farming exposure                          0.85 (95% CI: 0.59--1.23)
Farmers                                   0.97 (95% CI: 0.56--1.68)
Farming, foresty, gardening, & fishing    1.00 (95% CI: 0.61--1.63)
Farming occupation                        6.27 (95% CI: 1.83--21.5)
Agricultural indusnries                   4.18 (95% CI: 1.55--11.3)
Farming                                   0.56 (95% CI: 0.21--1.47)
Farmers & farm managers                   1.9 (95% CI: 0.6--5.4)
Farm workers                              8.6 (95% CI: 0.3--1.3)
Agricultural, foresty, & fishery workers
  All                                     0.9 (95% CI: 0.6-1.4)
  Seminoma                                0.4 (95% CI: 0.2-0.9)
Germ cell tumors                          1.1 (95% CI: 0.7--1.8)
Farming occupation                        1.59
Farming employment
  Current                                 0.6 (95% CI: 0.3--1.2)
  Ever                                    0.9 (95% CI: 0.6--1.4)
Farmers                                   113(95% CI: 105-122)
Farm workers                              109 (95% CI: 80--149)
Farmers
  White                                   1.18 (95% CI: 1.14--1.22)
  Nonwhite                                1.14 (95% CI: 1.05--1.24)
Farmers
  White                                   8.03 (95% CI: 0.57--1.17)
  Nonnwhite                               1.32 (95% CI: 0.48--2.88)
Farmers
  White                                   1.15 (95% CI: 0.73--2.14)
  Nonwhite                                1.35 (95% CI: 0.19--2.11)
Farmers
  White women                             1.01 (95% CI: 0.19--1.21)
  Nonwhite women                          0.68 (95% CI: 0.46--0.97)
  White men                               0,73 (95% CI: 0.43--1.16)
  Nonnwhite men                           1.72 (95% CI: 0.46--4.41)
Farmers
  White women                             0.78 (95% CI: 0.01--4.35)
  Nonwhite women                          1.14 (95% CI: 0.01--6.36)
  White men                               1.34 (95% CI: 0.95--1.83)
  Nonwhite men                            0.55 (95% CI: 0.01--3.04)
Farmers
  All cohorts                             1.14 (p [less than] .05)
  Born 1905--1958                         1.19 (p [greater than] .05)
Farmers
  All cohorts                             8.85 (p [greater than] .05)
  Born 1905--1958                         0.84 (p [greater than] .05)
Farmers
  White                                   1.1 (95% CI: 1.0--1.3)
  Nonwhite                                1.0 (95% CI: 0.8--1.2)
Farm workers
  White                                   101.4 (p [greater than] .05)
  Nonwhite                                93.1 (p [greater than] .05)
Farm owners & farm managers
  White                                   122.2 (p [less than] .01)
  Nonwhite                                81.7 (p [greater than] .05)
Farmers                                   1.10 (p [less than] .01)
                                          1.41 (p [less than] .01)
Farmers
  White                                   1.57 (p [less than] .01)
  Nonwhite                                0.86 (p [greater than] .05)

Meta-analysis
Farmers                                   1.08 (95% CI: 1.06--1.11)
Farmers                                   0.88 (95% CI: 0.79--1.03)
Female farmers                            1.02 (95% CI: 0.81--1.18)



Farming exposure                          Swerdlow et al. (1991)
Farmers                                   Jensen et al. (1984)
Farming, foresty, gardening, & fishing    Jensen et al. (1984)
Farming occupation                        Mills et al. (1984)
Agricultural indusnries                   Mills et al. (1984)
Farming                                   Sewell et al. (1986)
Farmers & farm managers                   Van den Eeden et al. (1991)
Farm workers                              Van den Eeden et al. (1991)
Agricultural, foresty, & fishery workers  Hayes et al. (1990)
  All
  Seminoma
Germ cell tumors
Farming occupation                        Graham & Gihson (1972)
Farming employment                        Brown & Pottern (1984)
  Current
  Ever
Farmers                                   Gallagher et al. (1984a)
Farm workers                              Gallagher et al. (1984h)
Farmers                                   Blair et al. (1993)
  White
  Nonwhite
Farmers                                   Blair et al. (1993)
  White
  Nonnwhite
Farmers                                   Blair et al. (1993)
  White
  Nonwhite
Farmers                                   Blair et al. (1993)
  White women
  Nonwhite women
  White men
  Nonnwhite men
Farmers                                   Blair et al. (1993)
  White women
  Nonwhite women
  White men
  Nonwhite men
Farmers                                   Saftlas et al. (1981)
  All cohorts
  Born 1905--1958
Farmers                                   Saftlas et al. (1987)
  All cohorts
  Born 1905--1958
Farmers                                   Delzell & Grufferman (1985)
  White
  Nonwhite
Farm workers                              Stubbs et al. (1984)
  White
  Nonwhite
Farm owners & farm managers               Stubbs et al. (1984)
  White
  Nonwhite
Farmers                                   Burmeister (1981)

Farmers                                   Une et al. (1981)
  White
  Nonwhite

Meta-analysis
Farmers                                   Davis et al. (1992)
Farmers                                   Davis et al. (1992)
Female farmers                            Davis et al. (1992)



cRR = combined relative risk.

CI:confidence interval.

OR = odds ratio.

PMR = proportional mortality ratio.

RR = relative risk.

SIR = standardized in CI:dence ratio.

SMR = standardized mortality ratio.
TABLE 3

Hormonal Cancers and Pesticide Exposure


Study Group                               Place of Study  Cancer Site

Retrospective follow-up study
Acres of insecticides sprayed             Canada          Prostate
Acres of herbicides sprayed               Canada          Prostate
[greater than]250 acres herbicides        Canada          Prostate
 sprayed (45-69 year-olds)
Licensed pesticide applicators            Sweden          Prostate
Licensed pesticide applicators            Florida         Prostate

Aerial pesticide applicators              United States   Prostate
Flight instructors                        United States   Prostate
Licensed pesticide applicators            Sweden          Testis
Licensed pesticide applicators            Sweden          Testis
 All
 Born 935 or later
 Born before 1934

Case-control study
Pesticide use                             England         Prostate
Pesticide exposure                        Netherlands     Prostate
 Sometimes or frequently
 Frequently
Insecticide exposure                      Canada          Prostate
Pesticide exposure                        Hawaii          Prostate
Pesticide exposure in general population  North Carolina  Prostate

Pesticide exposure in farmers             North Carolina  Prostate

Herbicide exposure in general population  North Carolina  Prostate

Herbicide exposure in farmers             North Carolina  Prostate

Pesticide exposure                        England         Testis
Herbicide exposure                        England         Testis
Pesticide exposure                        Washington, DC  Testis
 All
 Seminoma
 Germ cell tumors
Herbicide exposure                        Italy           Ovary
  All
  [less than]55 years old
  [greater than]55 years old

Proportional mortality ratio study
Herbicide exposure                        Wisconsin       Prostate
 Low-production group
 Medium-production group
 High-production group
Insecticide exposure                      Wisconsin       Prostate
 Low-production group
 Medium-production group
 High-production group




Study Group                               Measurement Results

Retrospective follow-up study
Acres of insecticides sprayed             RR
Acres of herbicides sprayed               RR
[greater than]250 acres herbicides        RR
 sprayed (45-69 year-olds)
Licensed pesticide applicators            SIR
Licensed pesticide applicators            No. of cases

Aerial pesticide applicators              SMR
Flight instructors                        SMR
Licensed pesticide applicators            RR
Licensed pesticide applicators            SIR
 All
 Born 935 or later
 Born before 1934

Case-control study
Pesticide use                             OR
Pesticide exposure                        OR
 Sometimes or frequently
 Frequently
Insecticide exposure                      OR
Pesticide exposure                        OR
Pesticide exposure in general population  %

Pesticide exposure in farmers             %

Herbicide exposure in general population  %

Herbicide exposure in farmers             %

Pesticide exposure                        OR
Herbicide exposure                        OR
Pesticide exposure                        OR
 All
 Seminoma
 Germ cell tumors
Herbicide exposure                        OR
  All
  [less than]55 years old
  [greater than]55 years old

Proportional mortality ratio study
Herbicide exposure                        PMR
 Low-production group
 Medium-production group
 High-production group
Insecticide exposure                      PMR
 Low-production group
 Medium-production group
 High-production group




Study Group

Retrospective follow-up study
Acres of insecticides sprayed             0.84 (95% CI: 0.52-1.36)
Acres of herbicides sprayed               1.19 (95% CI: 0.98-1.48)
[greater than]250 acres herbicides        2.23 (95% CI: 1.30-3.84)
 sprayed (45-69 year-olds)
Licensed pesticide applicators            0.99 (95% CI: 0.80-1.22)
Licensed pesticide applicators            Observed number = 2,
                                          Expected number = 3.8
Aerial pesticide applicators              136 (95% CI: 44-317)
Flight instructors                        57 (95% CI: 6-207)
Licensed pesticide applicators            1.55 (95% CI: 0.92-2.45)
Licensed pesticide applicators
 All                                      1.09 (95% CI: 0.68-1.67)
 Born 935 or later                        1.02 (95% CI: 0.54-1.74)
 Born before 1934                         1.42 (95% CI: 0.61-2.80)

Case-control study
Pesticide use                             0.63 (95% CI: 0.28-1.42)
Pesticide exposure
 Sometimes or frequently                  0.84 (95% CI: 0.63-1.13)
 Frequently                               1.47 (95% CI: 0.88-2.46)
Insecticide exposure                      0.73 (95% CI: 0.54-0.98)
Pesticide exposure                        1.3 (95% CI: 0.8-2.0)
Pesticide exposure in general population  12.5% of cases exposed,
                                          7.8% of controls exposed
Pesticide exposure in farmers             13% of cases exosed,
                                          17% of controls exposed
Herbicide exposure in general population  10% of cases exposed
                                          6.3% of controls exposed
Herbicide exposure in farmers             10% of cases exposed
                                          13% of controls exposed
Pesticide exposure                        1.04 (95% CI: 0.61-1.77)
Herbicide exposure                        1.14 (95% CI: 0.67-1.94)
Pesticide exposure
 All                                      1.2 (95% CI: 0.4-1.2)
 Seminoma                                 0.1 (95% CI: 0-1.0)
 Germ cell tumors                         1.5 (95% CI: 0.9-2.7)
Herbicide exposure
  All                                     4.38 (95% CI: 1.90-10.07)
  [less than]55 years old                 9.14 (95% CI: 2.95-28.30)
  [greater than]55 years old              1.90 (95% CI: 0.38-7.51)

Proportional mortality ratio study
Herbicide exposure
 Low-production group                     1.33 (p [greater than] .05)
 Medium-production group                  1.23 (p [greater than] .05)
 High-production group                    1.12 (p [greater than] .05)
Insecticide exposure
 Low-production group                     1.18 (p [greater than] .05)
 Medium-production group                  1.40 (p [greater than] .05)
 High-production group                    1.08 (p [greater than] .05)




Study Group                               Authors

Retrospective follow-up study
Acres of insecticides sprayed             Morrison et al. (1993)
Acres of herbicides sprayed               Morrison et al. (1993)
[greater than]250 acres herbicides        Morrison et al. (1993)
 sprayed (45-69 year-olds)
Licensed pesticide applicators            Wiklud et al. (1989)
Licensed pesticide applicators            Blair et al. (1983)

Aerial pesticide applicators              Cantor & Booze (1991)
Flight instructors                        Cantor & Booze (1991)
Licensed pesticide applicators            Wiklud et al. (1986)
Licensed pesticide applicators            Dich et al. (1996)
 All
 Born 935 or later
 Born before 1934

Case-control study
Pesticide use                             Ewings & Bowie (1996)
Pesticide exposure                        Van der Gulden et al. (1995)
 Sometimes or frequently
 Frequently
Insecticide exposure                      Ficham et al. (1992)
Pesticide exposure                        Le Marchand et al. (1991)
Pesticide exposure in general population  Checkoway et al. (1987)

Pesticide exposure in farmers             Checkoway et al. (1987)

Herbicide exposure in general population  Checkoway et al. (1987)

Herbicide exposure in farmers             Checkoway et al. (1987)

Pesticide exposure                        Swerdlow et al. (1991)
Herbicide exposure                        Swerdlow et al. (1991)
Pesticide exposure                        Hayes et al. (1990)
 All
 Seminoma
 Germ cell tumors
Herbicide exposure                        Donna et al. (1984)
  All
  [less than]55 years old
  [greater than]55 years old

Proportional mortality ratio study
Herbicide exposure                        Saftlas et al. (1987)
 Low-production group
 Medium-production group
 High-production group
Insecticide exposure                      Saftals et al. (1987)
 Low-production group
 Medium-production group
 High-production group



CI: confidence interval.

OR odds ratio.

PMR = proportional mortality ratio.

RR = relative risk.

SIR = standardized incidence ratio.

SMR = standardized mortality ratio.
TABLE 4

Breast Cancer and Endocrine-Disrupting Pesticide Residues


Exposure                    No. of Cases/  Cases--Mean
                            Controls       (SD)

p,p'-DDE adipose tissue     9/5            1.53 (1.39) ppm
DDE breast fat tissue       14/21          1.23 (0.63) ppm
p,p'.DDE breast fat tissue  41/33          0.96 (0.63) ppm

p,p'-DDE breast fat tissue  20/20          1 877 (1 283) ng/g
p,p'.DDE serum              58/171         11.0 (9.1) ng/mL
DDE adipose tissue          18/17          1,310.6 (2,077.7) mg/kg
p,p'-DDE serum              150/150        43.3 (25.9) ppb
Summary analysis




Exposure                    Controls--Mean       Ratio of Means
                            (SD)                 (95% CI)

p,p'-DDE adipose tissue     4.32 (1.66) ppm      0.35 (0.18-0.70)
DDE breast fat tissue       1.25 (0.76) ppm      0.98 (0.68-1.43)
p,p'.DDE breast fat tissue  0.98 (0.89) ppm      0.98 (0.68-1.42)

p,p'-DDE breast fat tissue  1 174 (630) ng/g     1.60 (1.09-2.34)
p,p'.DDE serum              7.7 (6.8) ng/mL      1.43 (1.11-1.84)
DDE adipose tissue          765.3 (526.9) mg/kg  1.79 (0.83-3.88)
p,p'-DDE serum              43.1 (23.7) ppb      1.01 (0.88-1.14)
Summary analysis                                 1.08 (0.98-1.19)




Exposure                    Authors


p,p'-DDE adipose tissue     Wassermann et al. (1976)
DDE breast fat tissue       Unger et al. (1984)
p,p'.DDE breast fat tissue  Mussalo-Rauhamaa et
                            al. (1990)
p,p'-DDE breast fat tissue  Falck et al. (1992)
p,p'.DDE serum              Wolff et al. (1993)
DDE adipose tissue          Dewailly et al. (1994)
p,p'-DDE serum              Krieger et al. (1994)
Summary analysis            Adami et al. (1995)



CI = confidence interval.

SD = standard deviation.

NG = nanogram
TABLE 5

Hormonal Cancer and Individual Endocrine-Disrupting Pesticides


Study Group                                            Place of Study

Retrospective follow-up study
Chemical workers exposed to 2,4-D
Chemical workers exposed to 2,4-D                      United States
Workers in phenoxy herbicides plant                    Denmark
   All employees
   Manufacturing & packing employees
Workers in phenoy herbicides plant                     Denmark
   Compared with national rate with rural
   correction factor
Workers in MPCA & other phenoxy-acid herbicides plant  England
Compared with national rate
  Compared with national rate with rural
   correction factor
Workers exposed to chlorophenoxy herbicides or         10 countries
 chlorinated phenol
  Female
  Male
Workers exposed to chlorophenoxy herbicides            10 countries
 or chlorophenols
Female workers exposed so chlorophenoxy herbicides,    International
 chlorophenols, or dioxin

Prospective follow-up study
Men who sprayed 2,4-D and 2,4,5-T                      Finland


Case-control study
Agricultoral workers exposed so triazine               Italy
   Definitely exposed
   Possibly exposed

Ecologic study
Group of counties exposed to triazine                  Kentucky
   Low exposure (1991-1992 rates)
   Medium exposure
   High exposure
   Low exposure (1993-1994 rates)
   Medium exposure
   High exposure




Study Group                                            Cancer Site

Retrospective follow-up study
Chemical workers exposed to 2,4-D                      Prostate
Chemical workers exposed to 2,4-D                      Testis
Workers in phenoxy herbicides plant                    Prostate
   All employees
   Manufacturing & packing employees
Workers in phenoxy herbicides plant                    Ovary
   Compared with national rate with rural
   correction factor
Workers in MPCA & other phenoxy-acid herbicides plant  Testis
Compared with national rate
  Compared with national rate with rural
   correction factor
Workers exposed to chlorophenoxy herbicides or         Breast
 chlorinated phenol
  Female
  Male
Workers noposed so chlnrophenony herbicides            Thyroid
 or chlorophenols
Female worlxers exposed to chlorophenoxy herbicides,   Breast
 chlorophenols, or dioxin

Prospective follow-up study
Men who sprayed 2,4-D and 2,4,5-T                      Prostate


Case-control study
Agricultoral workers exposed so triazine               Ovary
   Definitely exposed
   Possibly exposed

Ecologic study
Group of counties exposed to triazine                  Breast
   Low exposure (1991-1992 rates)
   Medium exposure
   High exposure
   Low exposure (1993-1994 rates)
   Medium exposure
   High exposure




Study Group                                            Measurement

Retrospective follow-up study
Chemical workers exposed to 2,4-D                      SMR
Chemical workers exposed to 2,4-D                      SMR
Workers in phenoxy herbicides plant                    RR
   All employees
   Manufacturing & packing employees
Workers in phenoxy herbicides plant                    RR
   Compared with national rate with rural
   correction factor
Workers in MPCA & other phenoxy-acid herbicides plant  SMR
Compared with national rate
  Compared with national rate with rural
   correction factor
Workers exposed to chlorophenoxy herbicides or         SMR
 chlorinated phenol
  Female
  Male
Workers exposed to chlorophenoxy herbicides            SMR
 or chlorophenols
Female workers exposed so chlorophenoxy herbicides,    SIR
 chlorophenols, or dioxin                              SMR

Prospective follow-up study
Men who sprayed 2,4-D and 2,4,5-T                      Number of cases


Case-control study
Agricultoral workers exposed so triazine               OR
   Definitely exposed
   Possibly exposed

Ecologic study
Group of counties exposed to triazine                  OR
   Low exposure (1991-1992 rates)
   Medium exposure
   High exposure
   Low exposure (1993-1994 rates)
   Medium exposure
   High exposure




Study Group                         Results

Retrospective follow-up study
Chemical workers exposed to 2,4-D   104 (95% CI: 1-576)
Chemical workers exposed to 2,4-D   462 (95% CI: 6-2569)
Workers in phenoxy herbicides
plant
   All employees                    0.83
   Manufacturing & packing          0.55
employees
Workers in phenoxy herbicides
plant
   Compared with national rate      132 (95% CI: 78-208)
with rural
   correction factor
Workers in MPCA & other
phenoxy-acid herbicides plant
Compared with national rate         236 (95% CI: 64-605)
  Compared with national rate with  223 (95% CI: 61-572)
rural
   correction factor
Workers exposed to chlorophenoxy
herbicides or
 chlorinated phenol
  Female                            30 (95% CI: 1-166)
  Male                              345 (95% CI: 42-1246)
Workers exposed to chlorophenoxy    367 (95% CI: 100-940)
herbicides
 or chlorophenols
Female workers exposed to           91 (95% CI: 36-187)
chlorophenoxy herbicides,
 chlorophenols, or dioxin           30

Prospective follow-up study
Men who sprayed 2,4-D and 2,4,5-T   Observed = 2,
                                    Expected = 1.1

Case-control study
Agricultoral workers exposed so
triazine
   Definitely exposed               2.8 (98% CI: 0.9-8.4)
   Possibly exposed                 2.1 (90% CI: 0.8-5.4)

Ecologic study
Group of counties exposed to
triazine
   Low exposure (1991-1992 rates)   1.00
   Medium exposure                  1.09 (95% CI: 1.04-1.14)
   High exposure                    1.07 (95% CI: 1.01-1.14)
   Low exposure (1993-1994 rates)   1.00
   Medium exposure                  1.14 (95% CI: 1.08-1.19)
   High exposure                    1.20 (95% CI: 1.13-1.28)




Study Group                         Authors

Retrospective follow-up study
Chemical workers exposed to 2,4-D   Bond et al. (1988)
Chemical workers exposed to 2,4-D   Bond et al. (1988)
Workers in phenoxy herbicides       Lynge (1985)
plant
   All employees
   Manufacturing & packing
employees
Workers in phenoxy herbicides       Lynge (1985)
plant
   Compared with national rate
wish roral
   correction factor
Workers in MPCA & other             Coggon et al. (1986)
phenoxy-acid herbicides plant
Compared with national rate
  Compared with national rate with
rural
   correction factor
Workers exposed to chlorophenoxy    Saracci et al. (1991)
herbicides or
 chlorinated phenol
  Female
  Male
Workers exposed to chlorophenoxy    Saracci et al. (1991)
herbicides
 or chlorophenols
Female workers exposed so           Kogevinas et al. (1993)
chlorophenoxy herbicides,
 chlorophenols, or dioxin

Prospective follow-up study
Men who sprayed 2,4-D and 2,4,5-T   Riihimaki et al. (1982)


Case-control study
Agricultoral workers exposed so     Donna et al. (1989)
triazine
   Definitely exposed
   Possibly exposed

Ecologic study
Group of counties exposed to        Kettles et al. (1997)
triazine
   Low exposure (1991-1992 rates)
   Medium exposure
   High exposure
   Low exposure (1993-1994 rates)
   Medium exposure
   High exposure



CI = confidence interval.

OR = odds ratio.

RR = relative risk.

SIR = standardized incidence ratio.

SMR = standardized mortality ratio.