Table 1.

Key characteristics of epidemiologic cohort and case-control studies of TCE exposure included in the meta-analysis.

Reference	Study Design	Study population and size		Outcome and Sites Examined	Exposure assessment and exposure surrogate
Anttila et al. [38]	C	Finnish workers (n = 3,974) biologically monitored using U-TCA (n = 3,089), 1965–1982, FU 1965–1991 (M), 1967–1992 (I).	I, M	K, L, NHL	Subjects from several industries, primarily metal. Using the Ikeda et al. [54] relationship for TCE exposure to U-TCA, TCE exposures were roughly 4 ppm (median) and 6 ppm (mean). Overall TCE exposure, mean U-TCA, years since 1st U-TCA measurement.
Axelson et al. [37]	C	Swedish workers biologically monitored using U-TCA (n = 1,670), 1955–1975, FU 1958–1987 (I).	I	K, L, NHL	Roughly ¾ of cohort had U-TCA concentrations equivalent to <20 ppm TCE. Overall TCE exposure mean U-TCA, years since 1st biological monitoring measurement.
Boice et al. [41]	C	Aircraft-manufacturing workers with ≥1 year at Lockheed Martin (Burbank, CA) (n = 77,965; 2,267 with routine TCE; 3,176 with intermittent TCE), FU 1960–1996.	M	K, L, NHL	TCE subcohort. JEM for potential TCE exposure for (1) routine or (2) intermittent or routine basis without semi-quantitative intensity estimate. Overall TCE exposure, exposure duration.
Boice et al. [26]	C	Aerospace workers with ≥6 months employment at Rockwell/ Rocketdyne (Santa Susana Field Laboratory and nearby facilities) (n = 41,351; 1,111 with TCE exposure), FU 1948–1999. Overlaps cohort of Zhao et al. [25].	M	K, L, NHL	TCE subcohort. Potential TCE exposure assigned to test-stand workers whose tasks included the cleaning or flushing of rocket engines (engine flush) (n = 639 subjects) or for general utility cleaning (n = 472). JEM for TCE without semi-quantitative intensity estimates. Vapor degreasing with TCE before 1966 and PCE afterwards. Overall TCE exposure, exposure duration.
Brüning et al. [49]	CC	Histologically confirmed RCC (n = 134), from hospitals (Arnsberg, Germany), 1992−2000; hospital controls (n = 401).	I	K (RCC)	Self-reported exposure and JEM of Pannett et al. [55] to assign cumulative exposure to TCE and PCE. Cumulative exposure, exposure duration.
Charbotel et al. [50]	CC	RCC (n = 87), from urologists’ files and area teaching hospitals (Arve Valley region, France), 1993–2003; urologist or general practitioner patient controls (n = 316).	I	K (RCC)	Semi-quantitative cumulative TCE exposure and presence/absence of peak TCE exposure assigned to subjects using a JTEM designed using information obtained from questionnaires and routine atmospheric monitoring of workshops or biological monitoring (U-TCA) of workers carried out since the 1960s. Cumulative exposure (low, 62.4 ppm-year; medium, 253.2 ppm-year; high, 925.0 ppm-year), cumulative exposure + peaks.
Cocco et al. [21]	CC	Histologically confirmed NHL from 7 European countries (Czech Republic, Finland, France, Germany, Ireland, Italy, and Spain) (n = 2,348), 1998−2004; hospital (4 participating countries) or population controls (all others) (n = 2,462).	I	NHL	IH assessment of 43 agents, including TCE, by confidence, exposure intensity, and exposure frequency, in each participating center. Overall TCE exposure, cumulative TCE exposure for subjects assessed with high degree of confidence.
Dosemeci et al. [51]	CC	Histologically confirmed RCC (n = 438), 1988−1990, Minnesota Cancer Registry; controls identified using RDD or, if ≥65 years, from HCFA records (n = 687).	I	K (RCC)	Occupational history of TCE exposure using job title and JEM of Gomez et al. [56]. Overall TCE exposure.
Greenland et al. [42]	Nested CC	Cancer deaths among pensioned workers, GE transformer plant (Pittsfield, MA) (n = 12 kidney, 9 liver and biliary, 15 NHL), 1969–1984; controls were non-cancer deaths among pensioned workers (n = 1,202).	M	K, L, NHL	IH assessment from interviews and position descriptions. TCE (no/any exposure) assigned to individual subjects using JEM. Overall TCE exposure.
Hansen et al. [39]	C	Workers biologically monitored using U-TCA and air-TCE (n = 803), 1947–1989, FU 1968–1998.	I	K, L, NHL	U-TCA from 1947−1989; air TCE measurements from 1974. Overall, TCE exposure to cohort as extrapolated from air TCE and U-TCA measurements, using Ikeda et al. [54], was 4 ppm (median) and 12 ppm (mean). Overall TCE exposure, year 1st employed, employment duration, mean exposure, cumulative exposure.
Hardell et al. [46]	CC	Histologically confirmed cases of NHL in males from Swedish (Umea) hospital (n = 105), 1974−1978; population controls or, if case deceased, from causes-of-death registry (n = 335).	I	NHL	Self-reported overall TCE exposure.
Miligi et al. [20]	CC	NHL, including CLL, cases (n = 1,428) identified through surveys of hospital and pathology departments or specialized hematology centers in 8 areas in Italy, 1991−1993; population controls (n = 1,530).	I	NHL+ CLL	TCE exposure assigned using JEM and assessed using exposure probability, intensity and duration. TCE exposure intensity, exposure duration.
Moore et al. [24]	CC	Histologically confirmed RCC identified in hospitals in four European countries (Czech Republic, Poland, Romania, Russia) (n = 1,097), 1999−2003; hospital controls with diagnoses unrelated to smoking or genitourinary disorders (n = 1,476).	I	K (RCC)	Specialized job-specific questionnaire for specific jobs or industries of interest focused on solvent exposures, includingTCE, with exposure assignment by frequency, intensity and confidence of TCE exposure. Overall TCE exposure, duration (total hours, years), cumulative exposure (cases: 0, 0.83, 1.95, 7.25 ppm-years for 25th percentile, median, and 75th percentile) and average intensity (cases: 0, 0.08, 0.08, and 0.44 ppm for 25th percentile, median, and 75th percentile).
Morgan et al. [43]	C	Aerospace workers with >6 months during 1950–1985 at Hughes (Tucson, AZ) (n = 20,503; 4,733 with TCE exposure), FU 1950–1993.	M	K, L, NHL	TCE subcohort. TCE exposure intensity assigned using JEM. “High TCE exposure” job classification defined as >50 ppm. Overall TCE exposure, cumulative exposure, peak exposure.
Nordstrom et al. [47]	CC	Histologically confirmed cases of hairy-cell leukemia in males (n = 111), Swedish Cancer Registry, 1987−1992;a population controls (n = 400).	I	NHL (HCL)	Self-reported overall TCE exposure.
Persson and Fredrikson [48]	CC	Histologically confirmed B-cell NHL from two hospitals in Sweden: Oreboro, 1964−1986, or Linkoping, 1975−1984 (n = 199); controls from previous studies, randomly selected from population registers (n = 479).	I	NHL	Self-reported overall TCE exposure.
Pesch et al. [52]	CC	Histologically confirmed RCC from German hospitals (5 regions) (n = 935), 1991−1995; controls randomly selected from residency registries (n = 4,298).	I	K (RCC)	TCE and other exposures assigned by questionnaire assessing occupational history using job title (JEM approach), job task (JTEM approach), or self-reported exposure. Cumulative exposure.
Purdue et al. [22]	CC	Histologically confirmed NHL identified from four SEER areas (Los Angeles County, Detroit metropolitan area, Seattle-Puget Sound and Iowa) (n = 1,321), 1998–2000; population controls from RDD, or Medicare file, if ≥65 years (n = 1,057).	I	NHL	Specialized job-specific modules asked for detailed information on individual jobs and focused on solvent exposures, including TCE; assessment by expert industrial hygienist blinded to case and control status by levels of probability, frequency, and intensity. Overall exposure, average weekly exposure, years exposed, average exposure intensity, and cumulative exposure. Cumulative exposure categories of 0, 1–46,800 ppm-hour, 46,801–112,320 ppm-hour, 112,321–234,000 ppmhour and >234,000 ppm-hour.
Radican et al. [27] (mortality follow-up of Blair et al. [44])	C	Civilian aircraft-maintenance workers with at least 1 year in 1952−1956 at Hill Air Force Base (UT) (n = 14,455; 7,204 ever exposed to TCE), FU 1952–2000 (M), 1973–1990 (I).	I, M	K, L, NHL	TCE assigned to individual subjects using JEM. TCE replaced in 1968 with 1,1,1-trichloroethane in bench-top degreasing activities and was discontinued in 1978 in vapor degreasing activities. Median TCE exposures were ~10 ppm for rag and bucket; 100−200 ppm for vapor degreasing. Overall TCE exposure, cumulative exposure, continuous or intermittent exposures, and peak exposure. Cumulative exposure categories of 0–5 unit-hour, 5–25 unit-hour, and >25 unit-hour.
Raaschou-Nielsen et al. [40]	C	Blue-collar workers employed >1,968 at 347 Danish TCE-using companies (n = 40,049; 14,360 with presumably higher-level exposure to TCE). FU to 1997.	I	K, L, NHL	Employers had documented TCE usage but no information on individual subjects, with job type and company size as variables identified as increasing the likelihood for TCE exposure. Subjects from iron and metal, electronics, painting, printing, chemical, and dry-cleaning industries. Median exposures to TCE were 40−60 ppm for the years before 1970, 10−20 ppm for 1970 to 1979, and approximately 4 ppm for 1980 to 1989. Overall TCE exposure, employment duration, year 1st employed, and company size.
Siemiatycki [53]	CC	Histologically confirmed NHL or kidney cancer in males, diagnosed in 16 large Montreal-area hospitals (215 = NHL, 177 K), 1979−1985; population-based controls identified from electoral lists and RDD (n = 533).	I	K, NHL	TCE and other exposure assigned on semi-quantitative scale from work histories by team of chemists and industrial hygienists. Overall TCE exposure, substantial exposure.
Wang et al. [23]	CC	Histologically confirmed NHL cases among females (n = 601), Connecticut Cancer Registry, 1996−2000; population-based female controls from RDD or, if ≥65 years of age, random selection from Medicare and Medicaid Service files (n = 717).	I	NHL	TCE intensity and probability of exposure assigned on semi-quantitative scale using JEM (Gomez et al. [56]). Overall TCE exposure, intensity, exposure probability.
Zhao et al. [25]	C	Aerospace workers with >2 years of employment at Rockwell/ Rocketdyne’s Santa Susana Field Laboratory, 1950–1993, FU 1950–2001 (M, n = 6,044), 1988–2000 (I, n = 5,049). Overlaps cohort of Boice et al.[26].	I, M	K, NHL+ other LHP cancers	TCE and other exposures assigned on semi-quantitative scale from work history using JEM. Cumulative TCE score.

^aUpon a review of the case series, Nordstrom et al. [47] found one case was diagnosed in 1993.

C = cohort, CA = California, CC = case-control, CLL = chronic lymphocytic leukemia, FU = follow-up, HCFA = Health Care Financing Administration, HCL = hairy cell leukemia, I = incidence, IH = industrial hygiene, JEM = job-exposure matrix, JTEM = job-task-exposure matrix, K = kidney cancer, L = liver and biliary tract cancer, LHP = lymphohematopoietic, M = mortality, MA = Massachusettes, NHL = non-Hodgkin lymphoma, PCE = perchloroethylene, ppm = parts per million, RCC = renal cell carcinoma, RDD = random digit dialing, TCE = trichloroethylene, US = United States, U-TCA = urinary trichloroacetic acid, UT = Utah.