6
CANCER AND EXPOSURE TO SOLVENTS

INTRODUCTION

The associations between exposure to organic solvents and the incidence of and mortality from cancer have been investigated extensively in a number of industries and occupations, including dry-cleaning, painting, printing, and rubber and shoe manufacturing. As a result, the body of evidence on exposure to organic solvents and cancer reviewed by the committee is quite large compared with that on other health effects. To help the reader become more familiar with the studies on exposure to solvents and cancer, this chapter is organized differently from Chapter 5.

Following this general introduction is a description of the major occupational cohort studies that are cited throughout the chapter; these studies provide findings for multiple cancer outcomes. The committee describes the essential study design characteristics and pertinent information for each of these cohorts organized by the type of solvent exposure.

The occupational cohort studies examined populations with known or suspected exposure to the solvents under review. Many of them have been updated and expanded to include more cohort members, longer periods of assessment, and other estimates of exposure. All of the various studies that follow a particular cohort, such as the NIOSH Pliofilm cohort, are described together in Table 6.1. The committee reviewed all the papers related to each major cohort in drawing its conclusions of association, but it is usually the findings from the most recent papers that are provided in the data-analysis tables at the end of the section on each cancer site. In some cases, results from the earlier papers were never reproduced, so the committee used the earlier results in its analysis.

A description of key case-control studies at the beginning of each section is followed by a table that outlines the studies’ characteristics and design elements and is similar to the table of cohort studies at the beginning of the chapter. Discussions of strengths and limitations of the studies that formed the basis of the committee’s conclusions are presented in the sections on the specific outcomes.

Background information on the types of cancer or cancer in general is provided in Chapter 5, and the reader is referred to those sections for that information. A review of the pertinent toxicology and findings from other organizations charged with evaluating the carcinogenicity of organic solvents is provided at the end of this introduction.

As in Chapter 5, the cancer outcomes are presented in the order of the ninth revision of the International Classification of Disease (ICD-9).

The Literature on Exposure to Organic Solvents

The literature on exposure to organic solvents and cancer outcomes provides information on specific solvent exposures (for example, benzene, trichloroethylene, and



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Gulf War and Health: Insecticides and Solvents, Volume 2 6 CANCER AND EXPOSURE TO SOLVENTS INTRODUCTION The associations between exposure to organic solvents and the incidence of and mortality from cancer have been investigated extensively in a number of industries and occupations, including dry-cleaning, painting, printing, and rubber and shoe manufacturing. As a result, the body of evidence on exposure to organic solvents and cancer reviewed by the committee is quite large compared with that on other health effects. To help the reader become more familiar with the studies on exposure to solvents and cancer, this chapter is organized differently from Chapter 5. Following this general introduction is a description of the major occupational cohort studies that are cited throughout the chapter; these studies provide findings for multiple cancer outcomes. The committee describes the essential study design characteristics and pertinent information for each of these cohorts organized by the type of solvent exposure. The occupational cohort studies examined populations with known or suspected exposure to the solvents under review. Many of them have been updated and expanded to include more cohort members, longer periods of assessment, and other estimates of exposure. All of the various studies that follow a particular cohort, such as the NIOSH Pliofilm cohort, are described together in Table 6.1. The committee reviewed all the papers related to each major cohort in drawing its conclusions of association, but it is usually the findings from the most recent papers that are provided in the data-analysis tables at the end of the section on each cancer site. In some cases, results from the earlier papers were never reproduced, so the committee used the earlier results in its analysis. A description of key case-control studies at the beginning of each section is followed by a table that outlines the studies’ characteristics and design elements and is similar to the table of cohort studies at the beginning of the chapter. Discussions of strengths and limitations of the studies that formed the basis of the committee’s conclusions are presented in the sections on the specific outcomes. Background information on the types of cancer or cancer in general is provided in Chapter 5, and the reader is referred to those sections for that information. A review of the pertinent toxicology and findings from other organizations charged with evaluating the carcinogenicity of organic solvents is provided at the end of this introduction. As in Chapter 5, the cancer outcomes are presented in the order of the ninth revision of the International Classification of Disease (ICD-9). The Literature on Exposure to Organic Solvents The literature on exposure to organic solvents and cancer outcomes provides information on specific solvent exposures (for example, benzene, trichloroethylene, and

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Gulf War and Health: Insecticides and Solvents, Volume 2 tetrachloroethylene), on mixtures of specific organic solvents, or on mixtures of unspecified solvents. In many studies, exposure to solvents was not assessed specifically; rather, surrogates of exposure were used, such as job title, industry type, or occupation. As is discussed in Chapter 2, a study’s ability to determine exposure accurately and specifically is critical in evaluating its overall quality. For the purposes of this report, the committee used studies that assessed exposure to specific organic solvents or to solvent mixtures as the primary evidence for its conclusions. The committee also included surrogates of exposure in drawing its conclusions, but it viewed those studies as supportive or supplemental evidence. Those studies included exposure of painters, printers, aircraft maintenance and manufacturing workers, service-station attendants, and shoe and boot manufacturers. All those studies are included in the data-analysis tables that accompany discussions of each cancer outcome. The committee found most of the cancer literature focused on the following compounds: benzene, trichloroethylene, tetrachloroethylene, methylene chloride, and mixtures of unspecified organic solvents. Therefore, most of the committee’s conclusions on cancer outcomes are focused on exposure to those compounds. A smaller number of studies analyzed associations between cancer outcomes and toluene, xylene, isopropyl alcohol, methyl ethyl ketone, phenol, and other individual solvents, but for most agents, there was insufficient evidence for the committee to draw conclusions. For exposure to tetrachloroethylene, the committee included studies of dry-cleaning and laundry workers as part of the primary evidence in drawing conclusions of associations. As a result, the conclusions related to exposure to tetrachloroethylene are also related to exposure to “dry-cleaning solvents.” The committee acknowledges that dry cleaners and launderers are likely exposed to other organic solvents and chemicals, including naphtha, Stoddard solvent, carbon tetrachloride, trichloroethylene, and 1,1,1-trichloroethane (IARC, 1995). As a result, the committee decided to consider studies of both tetrachloroethylene and dry-cleaning solvents in forming their conclusions, thereby including the possibility that one of the other solvents used in that industry contributed to the risks observed in some of the studies on dry cleaners and launderers. The committee based its review of cancer outcomes only on studies of humans that had a comparison or control group (cohort and case-control studies). Case reports, case series, review articles, and meta-analyses related to cancer were excluded from the committee’s review. Although the committee reviewed ecologic, cross-sectional, proportionate mortality ratio (PMR), and mortality odds ratio studies, it did not consider them critical to its decision and excluded them from the discussions. Chapter 2 describes their specific limitations. Toxicity and Determination of Carcinogenicity Excess incidence of cancer has been observed in animals exposed to the specific organic solvents reviewed by the committee. Benzene, perhaps the most thoroughly investigated solvent, is a well-established carcinogen and has repeatedly been shown to induce hematopoietic cancers and cancers of the ovaries, mammary glands, pancreas, and liver (ATSDR, 1997a). The International Agency for Research on Cancer (IARC) has determined that benzene is “carcinogenic to humans” as determined in studies of both humans and animals. IARC bases its determination of benzene’s carcinogenicity on evidence from human studies that is considered “sufficient,” whereas the available animal

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Gulf War and Health: Insecticides and Solvents, Volume 2 data are considered “limited.” Most of the human studies cited by IARC involve the increased risk of leukemia and other lymphatic and hematopoietic cancers (IARC, 1987). The National Toxicology Program (NTP) has also classified benzene as “known to be a human carcinogen” in its most recent report on carcinogens on the basis of animal and human studies (NTP, 2001). On the basis of animal studies, trichloroethylene has been associated with liver cancer in one strain of one species (mouse) (ATSDR, 1997b). Liver and renal cell cancers and mononuclear cell leukemia have typically been seen after exposure to tetrachloroethylene. According to the Agency for Toxic Substance and Disease Registry (ATSDR, 1997c), the relevance to humans of rodent toxicology studies on trichloroethylene and tetrachloroethylene is unclear, given that some mechanisms of action differ. However, a great deal of research has been conducted over the last decade, and some mechanisms of action appear to be similar in rodents and humans such as genotoxic and cytotoxic actions of mercapturic acid derivatives of both trichloroethylene and tetrachloroethylene in the kidney (see Chapter 4 for more information). IARC has also reviewed trichloroethylene and tetrachloroethylene and determined that both are “probably carcinogenic to humans.” The evidence from animal studies is stronger and considered to be “sufficient,” whereas the evidence from human studies is considered “limited” (IARC, 1995). In addition, the NTP has identified both trichloroethylene and tetrachloroethylene as “reasonably anticipated to be human carcinogens” (NTP, 2001). Exposure to methylene chloride in some rodent species has consistently produced excess numbers of cancers of the liver and lung and benign mammary tumors (ATSDR, 2000). IARC has determined that exposure to methylene chloride is “possibly carcinogenic to humans,” and the NTP concluded that it is “reasonably anticipated to be a human carcinogen” (IARC, 1999; NTP, 2001). IARC has determined that toluene and xylene are “not classifiable as to their carcinogenicity to humans” in that there was inadequate evidence from studies of humans and animals (IARC, 1999). Chloroform has produced liver and kidney tumors in a strain-, sex-, species-, and dose-dependent manner and, on the basis of sufficient evidence from animal studies, is “reasonably anticipated to be a human carcinogen” according to the NTP (ATSDR, 1997d; NTP, 2001). Chloroform was once used as an anesthetic, but its association with cancer in nonmedical exposures in humans has not been investigated extensively. The committee did not review studies on the efficacy of solvents as therapeutic agents (see Chapter 2). Chapter 4 provides details on the adverse effects of chloroform as observed in experimental studies. In addition to evaluating the carcinogenicity of specific chemical agents, IARC has analyzed whether particular occupations pose a greater risk for exposure to carcinogenic agents. In fact, IARC has determined that working in the rubber industry and in boot and shoe manufacturing and repair pose such a risk (IARC, 1987), and it determined that there is “sufficient evidence for the carcinogenicity of occupational exposure as a painter” (IARC, 1989). Although IARC identifies exposures of concerns and specific cancer outcomes that demonstrate an increased risk, its overall charge is to determine whether a specific agent or occupation is carcinogenic, not whether an agent causes a specific cancer outcome. It is important to distinguish the objectives of IARC’s program and the charge of the present committee. The purpose of the IARC program is to determine whether agents or occupational exposures are carcinogenic, whereas this committee is charged with determining whether there is an association between exposure to a specific agent and

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Gulf War and Health: Insecticides and Solvents, Volume 2 chronic human illnesses. As discussed earlier in this report, the committee uses experimental evidence only when it is required by the definitions of the categories of association. Only the category of “Sufficient Evidence of a Causal Association” requires support from experimental evidence. For each conclusion of causality, the animal data that provides a plausible mechanism for the outcome being discussed are described—as in the section on chronic exposure to benzene and acute leukemia. Additional information on the toxicology and available experimental data on a number of solvents reviewed in this report can be found in Chapter 4. DESCRIPTION OF THE COHORT STUDIES In reviewing the published epidemiologic literature on exposure to organic solvents, the committee examined a number of occupational cohort studies that provided information on the association between cancer mortality or incidence and exposure to specific organic solvents or to mixtures of organic solvents. Deaths or incident cases of cancer in the cohort studies were recorded, exposed populations were followed over time, and the relationship between rates of cancer and exposure was assessed with statistical methods. Because the cohort studies played an important role in the committee’s conclusions and are referred to throughout this chapter, they are described here according to the solvents they examined. Table 6.1 presents for each study a description of the population, the followup period, the number of subjects, the relevant exposures, the methods used to assess exposure to organic solvents, the statistical methods, and the adjustment for potential confounding variables. Similar tables for case-control studies are found in the sections on each type of cancer. Studies of Workers Exposed to Benzene Benzene is used in chemical processes often as an intermediate in the manufacture of other chemicals and end products. Occupational exposure to benzene has been studied primarily in industrial workers, including rubber, chemical, and petroleum and gasoline workers. On the basis of human studies of those occupational groups and animal studies over the last 60 years, the allowable occupational health standard for benzene has steadily decreased in the United States. In 1987, the permissible exposure limit (PEL) set by the Occupational Safety and Health Administration (OSHA) was reduced from 10 parts per million (ppm) to a time weighted average over 8 hours (8-hr TWA) of 1 ppm (NIOSH, 1997).

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Gulf War and Health: Insecticides and Solvents, Volume 2 TABLE 6.1 Description of Cohort Studies Related to Exposure to Organic Solvents Reference Description Study Group (N) Comparison Group (N) Exposure Assessment and Other Relevant Exposures Analysis and Adjustment for Potential Confounders Benzene NIOSH Pliofilm Cohort Infante et al., 1977 Mortality experience (1940–1975) of white male Pliofilm workers (at least 1 day in 1940–1949) at three Goodyear facilities in Ohio 748 (1) US white male population Employment in a benzene-exposed occupation as verified through historical air exposure measurements SMR Age, time period (2) 1447 white, male fibrous-glass construction workers in Ohio Rinsky et al., 1981 Mortality experience (1940–1975) of   US white male population Employment in a benzene-exposed occupation as verified through historical air exposure measurements SMR Age, sex, time period (1) the original cohort and (1) 748 (2) a second group of white male Pliofilm workers (at least 1 day in 1950–1959) (2) 258 at three Goodyear facilities in Ohio Rinsky et al., 1987 Mortality experience (1940–1981) of white male Pliofilm workers (at least 1 day in 1940–1965) at three Goodyear facilities in Ohio 1165 US white male population Employment in a benzene-exposed occupation as verified through historical air exposure measurements, with cumulative exposure indexes SMR Age, time period Paxton et al., 1994a, 1996 Mortality experience (1940–1987) of white male Pliofilm workers (at least 1 day in 1940–1965) at three Goodyear facilities in Ohio 1212 US white male population Employment in a benzene-exposed occupation as verified through modified historical air exposure measurements, with cumulative exposure indexes SMR Age, time period Paxton et al., 1994b Mortality experience (1940–1987) of white male Pliofilm workers (at least 1 day in 1940–1965) at three Goodyear facilities in Ohio 1868 US white male population Employment in a benzene-exposed occupation as verified through modified historical air exposure measurements, with cumulative exposure indexes SMR, Cox proportional hazards model Age, sex, location, time of first Pliofilm employment

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Gulf War and Health: Insecticides and Solvents, Volume 2 Reference Description Study Group (N) Comparison Group (N) Exposure Assessment and Other Relevant Exposures Analysis and Adjustment for Potential Confounders Crump, 1994, 1996 Mortality experience (1940–1987) of white male Pliofilm workers (at least 1 day in 1940–1965) at three Goodyear facilities in Ohio 1717 US white male population Employment in a benzene-exposed occupation as verified through modified historical air exposure measurements, with cumulative exposure indexes Life-table analysis Age, sex Wong, 1995 Mortality experience (1940–1987) of white male Pliofilm workers (at least 1 day in 1940–1965) at three Goodyear facilities in Ohio 1868 US general population Employment in a benzene-exposed occupation as verified through historical air exposure measurements, with cumulative exposure indexes SMR Age Chinese Workers Cohort Yin et al., 1987 Mortality experience (1972–1981) of benzene-exposed workers (at least 6 months) in China 28,460 total 15,643 men 12,817 women 28,257 unexposed Employment in a benzene-exposed occupation as verified through historical air exposure measurements from factory records RR, SMR Age, sex Yin et al., 1989 Mortality experience (1972–1981) of benzene-exposed workers (at least 6 months) in China 28,460 total 15,643 men 12,817 women 28,257 unexposed Employment in a benzene-exposed occupation as verified through historical air exposure measurements from factory records RR, SMR Age, sex, smoking Yin et al., 1994 Incidence and mortality experience (1972–1981) of benzene-exposed workers (at least 6 months) in China 28,460 total 15,643 men 12,817 women 28,257 unexposed Employment in a benzene-exposed occupation as verified through historical air exposure measurements from factory records SMR, Poisson Age, sex, time of first employment Li et al., 1994 Incidence and mortality experience (1972–1987) of benzene-exposed workers (at least 1 day) in China 74,828 total 38,833 men 35,995 women 35,805 unexposed Employment in a benzene-exposed occupation RR Sex

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Gulf War and Health: Insecticides and Solvents, Volume 2 Reference Description Study Group (N) Comparison Group (N) Exposure Assessment and Other Relevant Exposures Analysis and Adjustment for Potential Confounders Yin et al., 1996a,b Incidence and mortality experience (1972–1987) of benzene-exposed workers (at least 1 day) in China 74,828 total 38,833 men 35,995 women 35,805 unexposed Employment in a benzene-exposed occupation as verified through historical air exposure measurements from factory records RR Age, sex Hayes et al., 1996 Mortality experience (1972–1987) of benzene-exposed workers (at least 1 day) in China 74,828 total 38,833 men 35,995 women 35,805 unexposed Employment in a benzene-exposed occupation with cumulative exposure assigned by industrial hygienist from historical records RR (Poisson), trend analysis Age, sex Hayes et al., 1997 Incidence (1972–1987) in benzene-exposed workers (at least 1 day) in China 74,828 total 38,833 men 35,995 women 35,805 unexposed Employment in a benzene-exposed occupation with cumulative and average exposure assigned by industrial hygienist from historical records RR (Poisson) Age, sex Other Cohort Studies McMichael et al., 1976 Mortality experience (1964–1973) of male rubber workers (at least 1 day) in four plants in Ohio and Wisconsin 18,903 1968 US male population Employment at one of four rubber-manufacturing plants SMR Age, race Wilcosky et al., 1984 Cases, age 40–84 years, selected retrospectively from a cohort of active and retired male rubber workers in a plant in Akron, Ohio, in 1964–1973; an age-stratified, 20% random sample from the original cohort served as the control group NA 1336 (20% of 6678) Linkage of worker histories to plant solvent-use records; work in process area with known solvent use equates to exposure Race-specific ORs Age   Other exposures: trichloroethylene, tetrachloroethylene, toluene, xylenes, naphthas, ethanol, acetone, phenol  

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Gulf War and Health: Insecticides and Solvents, Volume 2 Reference Description Study Group (N) Comparison Group (N) Exposure Assessment and Other Relevant Exposures Analysis and Adjustment for Potential Confounders Pippard and Acheson, 1985 Mortality experience (1939–1982) of male boot and shoe manufacturers (in 1939) in three tow ns in Great Britain 5017 County general populations Job title SMR Age, time period   Other exposures: trichloroethylene, solvents Wong, 1987a Mortality experience (1946–1977) of male chemical workers (at least 6 months) in seven US plants 7676 US general population Job title and employment duration SMR, Mantel-Haenszel RR Age, race Wong, 1987b Mortality experience (1946–1977) of male chemical workers (at least 6 months) in seven US plants 7676 US general population Job title and employment duration SMR, Mantel-Haenszel RR Age, race Paci et al., 1989 Mortality experience (1939–1984) of shoe workers (at least 1 day) in Florence, Italy 2013 total 1008 men 1005 women Italy general population Plant production records and work histories SMR Age, sex, calendar year Walker et al., 1993 Mortality experience (1940–1982) of shoe-manufacturing workers (at least 1 month in 1940–1979) in Ohio 7814 total 2529 men 5285 women US general population Employment at one of two plants SMR Age, sex, race, time period   Other exposures: MEK, acetone, naphtha, isopropyl alcohol, methanol, ethylene glycol monoethyl ether, xylene   Greenland et al., 1994 White, male cases of cancer (multiple sites; died in 1969–1984) and controls in a cohort of transformer-assembly workers in Massachusetts 1821 cases 1202 controls Internal comparison Job titles rated for exposure by industrial hygienist Logistic OR (nested case-control)   Other exposures: trichloroethylene, solvents Age, death year, covariates that altered an estimate >20% Lagorio et al., 1994 Mortality experience (1981–1992) of self-employed gas-station attendants (in 1980) in Italy 2665 total 2308 men 357 women Latium region, Italy general population Environmental survey and duration of employment SMR Age, sex

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Gulf War and Health: Insecticides and Solvents, Volume 2 Reference Description Study Group (N) Comparison Group (N) Exposure Assessment and Other Relevant Exposures Analysis and Adjustment for Potential Confounders Heineman et al., 1995 Brain tumor incidence in women (1980–1984) in Shanghai, China 276 Shanghai general population Job title SIR Age Fu et al., 1996 Mortality experience (1939–1991) of shoe-manufacturing workers in England (1939) and Italy (1950–1984) 6223 total 5220 men 1003 women England and Italy general populations Job title SMR Age, sex, time period Schnatter et al., 1996a,b Cases of lymphohematopoietic cancers (died in 1964–1983) and controls in a cohort of Canadian petroleum-distribution workers 29 cases, matched 1:4 Internal comparison Industrial hygienist review based on work histories, site characterizations, surveys Mantel-Haenszel OR (nested case-control) Smoking, family cancer history, x-ray history Ireland et al., 1997 Mortality experience (1940–1991) of male US chemical-plant workers (at least 1 day in 1940–1977) in Monsanto company plant in Sauget, IL 4172 Illinois general population Industrial hygienist exposure estimates based on work records SMR Lynge et al., 1997 Incidence experience (1970–1991) in service-station workers (1970) in Denmark and Scandinavia 18,969 total 16,524 men 2445 women Nation general populations Job title SMR Age, sex Rushton and Romaniuk, 1997 Cases of leukemia and controls in a cohort of petroleum-distribution workers (1975–1992) in UK 91 cases, matched 1:4 Internal comparison Measurements factored in occupational hygiene estimates, work histories, job descriptions, fuel compositions OR (nested case-control), logistic regression Age, smoking, date of hire, employment duration, socioeconomic status

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Gulf War and Health: Insecticides and Solvents, Volume 2 Reference Description Study Group (N) Comparison Group (N) Exposure Assessment and Other Relevant Exposures Analysis and Adjustment for Potential Confounders Trichloroethylene Aircraft and Aerospace Workers Garabrant et al., 1988 Mortality experience (1958–1982) of aircraft-manufacturing workers (at least 1 day) at an aircraft-manufacturing facility in San Diego County, California (with at least 4 years of cumulative company employment) 14,067 total 11,898 men 2169 women US general population Employment determined through company work records and interviews SMR Age, sex, race, calendar year, duration of employment, year of death Spirtas et al., 1991 Mortality experience (1952–1982) of aircraft-maintenance workers (at least 1 year in 1952–1956) at Hill Air Force Base in Utah 14,457 total 10,730 men 3727 women Utah white population Industrial hygienist assessment from interviews, surveys, hygiene files, position descriptions SMR, trend analysis Age, sex, calendar period   Other exposures: Stoddard solvent, isopropyl alcohol, trichloroethane, acetone, toluene, MEK, methylene chloride   Blair et al., 1998 Incidence and mortality experience (1952–1990) of aircraft-maintenance workers (at least 1 year in 1952–1956) at Hill Air Force Base in Utah 14,457 total 10,730 men 3727 women Utah white population Industrial hygienist assessment from interviews, surveys, hygiene files, position descriptions SMR, RR (Poisson) Age, sex, calendar period   Other exposures: Stoddard solvent, isopropyl alcohol, trichloroethane, acetone, toluene, MEK, methylene chloride   Morgan et al., 1998 Mortality experience (1950–1993) of aerospace workers (at least 6 months) Hughes Aircraft plant in Arizona 20,508 total (4733 exposed) 13,742 men 6766 women US general population Exposure matrixes generated by employees and industrial hygienists SMR, Cox proportional hazards model Age, sex

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Gulf War and Health: Insecticides and Solvents, Volume 2 Reference Description Study Group (N) Comparison Group (N) Exposure Assessment and Other Relevant Exposures Analysis and Adjustment for Potential Confounders Boice et al., 1999 Mortality experience (1960–1996) of aircraft-manufacturing workers (at least 1 year) Lockheed Martin facility in California 77,965 total 62,477 men 15,488 women General California population of white workers Abstracted from walkthrough surveys, hygiene files, job descriptions SMR, RR (Poisson) Age, sex, race, dates of first and last employment   Other exposures: tetrachloroethylene, solvents Other Cohort Studies Axelson et al., 1978 Mortality experience (1955–1975) of Swedish men occupationally exposed during the 1950s and 1960s 518 Sweden general population Biologic monitoring for U-TCA RR Age Axelson et al., 1994 Mortality experience (1955–1986) of Swedish workers occupationally exposed during the 1950s and 1960s 1670 total 1421 men 249 women Sweden general population Biologic monitoring for U-TCA SMR, SIR (Poisson) Age, sex, time period Anttila et al., 1995 Incidence experience (1967–1992) of workers biologically monitored for occupational exposure to halogenated solvents (1965–1983) at the Finnish Institute of Occupational Health 3974 total 2050 men 1924 women Finland general population Biologic monitoring for U-TCA, and blood metabolites of tetrachloroethylene and trichloroethane SIR Age, sex, time period   Other exposures: trichloroethane, tetrachloroethylene   Ritz, 1999 Mortality experience (1951–1989) of male uranium-processing plant workers (at least 3 years, with first hire in 1951–1972) in Ohio 3814 (1) External comparison with US general population (2) Internal comparison among workers monitored for exposure Exposure matrixes generated by employees and industrial hygienists SMR, RR (conditional logistic regression) Age, calendar year, time since first hired, pay type, radiation dose

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