Table 3.

Epidemiologic studies of manufacturers and sprayers of herbicides potentially contaminated with TCDD

Author	Study subjects	Period of exposure and follow-up	Definition of outcome	Definition of exposure	Level of exposure (with N cases)	RR (95 % CI)	Comments
Ott and Zober [145]	243 male workers in German plant where an accident entailing releasing of TCDD occurred in 1953, who were involved in clean-up, repair, maintenance, or demolition activities; serum TCDD level available for all cohort members	Employment during 1953–1969 in accident-related activities; follow-up 1953–1992	Prostate cancer mortality from death certificates obtained through health and safety administration Incidence of prostate cancer from medical and hospital records and contacts with cohort members	Ever-employment in accident-related activities Exposure derived from serum TCDD levels: low (<0.1 µg/kg body weight), medium (0.1–0.99 µg/kg body weight), high (≥ 1 µg/kg body weight) 113 workers with chloracne	Exposed: 0 deaths Exposed: 4 incident cases Low exposure: 3 cases Medium exposure: 1 case High exposure: 0 cases	SMR = 0 (0–1.9) SIR = 1.1 (0.3–2.8) SIR = 2.5 (0.5–7.4) SIR = 1.1 (0–5.9) SIR = 0 (0–2.5)	Not included in the pooled analysis [17] No results on prostate cancer reported for chloracne sub-cohort
Kogevinas et al. [17]	21,863 male and female workers exposed to phenoxy herbicides and chlorophenols in manufacture or spraying; pooled analysis of 36 cohorts (32 manufacture, 4 spraying) from 12 countries (Austria, Australia, Canada, Denmark, Finland, Germany, Italy, the Netherlands, New Zealand, Sweden, United Kingdom, United States)	Employment and cancer mortality follow-up period varied by cohort and country; overall they extended during 1939–1992	Prostate cancer mortality from death certificates obtained from national mortality registries in 10 countries, place of residence (Italy) or contact to companies, insurance, physicians and family members (Germany)	Exposure to TCDD defined as (1) employment during manufacture of spraying of 2,4,5-T, PCP or other potentially contaminated compounds, or (2) employment in plants with documented (biomonitoring or environmental measurements) exposure to TCDD Biomonitoring data available for 573 workers from 10 cohorts 13,831 workers (63.3 %) classified as exposed to TCDD	Exposed: 43 deaths Unexposed: 25 deaths	Exposed: SMR = 1.11 (0.81–1.50) Unexposed: SMR = 1.10 (0.71–1.62)	–
Steenland et al. [136]	5,132 male workers employed in 12 U.S. plants manufacturing herbicides contaminated with TCDD	Ever employment during 1942–1984; follow-up 1942–1993	Prostate cancer mortality from death certificates obtained from National Death Index, Social Security Administration, and Internal Revenue Service	Ever employment in the plants Biomonitoring data available for 253 workers 630 workers with history of chloracne	Exposed: 28 deaths	SMR = 1.17 (0.78–1.69)	Included in the pooled analysis [17], with follow-up to 1987 No results on prostate cancer reported for chloracne sub-cohort
‘t Mannetje et al. [140]	1,025 male and female phenoxy herbicide production workers and 703 sprayers in New Zealand	Employment 1969–1984 (production workers; 813 exposed); registration 1973–1984 (sprayers; 699 exposed); follow-up 1969–2000	Prostate cancer mortality from national registry	Employment in herbicide production or spraying	Production: 1 death Spraying: 2 deaths	Production: SMR = 0.37 (0.01–2.08) Sprayers: SMR = 0.60 (0.07–2.16)	Included in the pooled analysis [17] with follow-up to 1986
Collins et al. [137]	773 male PCP manufacture workers with exposure to chlorinated dioxins, including 196 with exposure to TCDD, employed in one U.S. plant; serum TCDD level available for 128 workers	Employent during 1937–1980; period of follow-up unspecified	Prostate cancer mortality from death certificates	Ever-employment in PCP manufacture Estimated cumulative TEQ exposure estimated from serum levels of 5 dioxins and occupational history: low (<0.7 ppb-years), medium (0.7–3.99 ppb-years), high (4.0+ ppb-years)	Whole cohort: 8 deaths Excluding 196 TCP workers: 7 deaths Low exposure: 4 deaths Medium exposure: 2 deaths High exposure: 2 deaths Dose–response (per 1 ppb-year)	SMR = 1.0 (0.4–1.9) SMR = 1.0 (0.4–2.1) SMR = 0.8 (0.1–2.9) SMR = 0.6 (0.1–2.4) SMR = 1.4 (0.4–3.6) RR = 1.002 (0.962–1.045)	Included in the pooled analysis [17] with follow-up to 1987, and in the study by Steenland et al. [136] with follow-up to 1993
Collins et al. [138]	1,615 male TCP manufacture workers with exposure to TCDD employed in one U.S. plant, including 196 PCP production workers; serum TCDD level available for 280 workers	Employment during 1942–1982; follow-up 1942–2003	Prostate cancer mortality from death certificates	Ever-employment in TCP or 2,4,5-T manufacture	Whole cohort: 21 deaths Excluding PCP workers: 20 deaths	SMR = 1.4 (0.9–2.2) SMR = 1.5 (0.9–2.4)	Included in the pooled analysis [17] with follow-up to 1987, and in the study by Steenland et al. [136] with follow-up to 1993
McBride et al. [141]	1,754 male and female production workers in New Zealand	Employment during 1969–2003; follow-up 1969–2004	Prostate cancer mortality from national registry	Employment in herbicide production	Whole cohort: 3 deaths <3 months employment: 3 deaths 3+ months employment: 0 deaths <15 years since last worked: 0 deaths ≥15 years since last worked: 3 deaths Hired pre-1976: 3 deaths Hired post-1975: 0 deaths	SMR = 0.54 (0.11–1.56) SMR = 0.62 (0.13–1.82) SMR = 0.00 (0.00–4.67) SMR = 0.00 (0.00–4.83) SMR = 0.62 (0.13–1.81) SMR = 0.58 (0.12–1.68) SMR = 0.00 (0.00–9.36)	Included in the pooled analysis [17] with follow-up to 1986 and in the study by ‘t Mannetje et al. [140] with follow-up to 2000
McBride et al. [142]	1,599 male and female production workers in New Zealand	Employment during 1969–1988; follow-up 1969–2004	Prostate cancer mortality from national registry	Employment during 2,4,5-T production; 1,134 workers classified as TCDD exposed and 346 as unexposed	Exposed to TCDD: 1 death Unexposed to TCDD: 2 deaths	SMR = 0.2 (0.0–1.2) SMR = 1.9 (0.2–6.7)	Included in the pooled analysis [17] with follow-up to 1986 and in the study by ‘t Mannetje et al. [140] with follow-up to 2000; subset of population studies by McBride et al. [142]
Boers et al. [143, 146]	2,106 male workers in two Dutch plants, one with 2,4,5-T as main product (factory A) and the other with 4-chloro-2-methylphenoxyacetic acid, 4-chloro-3-methylphenoxy propanoic acid, and 2,4-D as main products (factory B); serum TCDD level available for 187 workers (101 from factory A, 86 from factory B)	Employment 1955–1985 (plant A), 1965–1986 (plant B); follow-up to 2006	Prostate cancer mortality from national registry	Employment in selected departments (or entering them on a regular basis), or exposure to an accident in factory A in 1963	Factory A Exposed: 6 deaths Unexposed: 2 deaths Factory B Exposed: 4 deaths Unexposed: 2 deaths	Factory A: HR = 2.93 (0.61–14.1) Factory B: HR = 2.68 (0.48–14.9) HR for ln TCDD level = 1.08 (0.79–1.49) in total cohort HR for ln TCDD level = 1.29 (0.85–1.94) in factory A	Included in the pooled analysis [17] with follow-up to 1986; 4 of 6 exposed cases in Factory A exposed to accident
Ruder and Yiin [139]	2,122 workers at 4 U.S. PCP production plants	Employment from 1930s until 1980s, one plant until 2005; follow-up 1940–2005	Prostate cancer mortality from death certificates	Employment in TCP production (exposure to TCDD, N = 720)	Exposed: 8 deaths Unexposed: 18 deaths Whites: 21 deaths Non-Whites: 5 deaths	Exposed: SMR = 1.08 (0.47–2.12) Unexposed: SMR = 1.01 (0.60–1.60) Whole cohort, whites: SMR = 1.04 (0.64–1.59) Whole cohort, non-whites: SMR = 1.00 (0.32–2.33)	Included in the pooled analysis [17] and in the study by Steenland et al. [136]; partial overlap with Collins et al. [138]
Manuwald et al. [144]	1,191 male production workers in Germany	Employment 1952–1984; follow-up 1952–2007	Prostate cancer mortality from death certificates obtained from local population registries	Ever-employment (minimum 3 months) in the plant	Ever employed: 19 deaths	SMR = 1.37 (0.82–2.13)	Included in the pooled analysis [17] with follow-up to 1987