Table 2.

Case-control studies of chlorophenoxy compounds and NHL.

NHL OR	Cases	Controls	Reference	Herbicide	Notes
4.8 (2.9–8.1)	41	24	Hardell et al. [72]	2,4,5-T; 2,4-D; MCPA	Chlorophenols, solvents, and other pesticides. Exposure defined as greater than one day; entirely self-reported. One documented MCPA exposure across cases; results for NHL and HD combined. Forestry.
4.9 (1.3–18)	6	6	Persson et al. [68]	Phenoxys	Chlorophenols, solvents, and other pesticides. Variety of occupations and exposure described by occupation. Exposure to wood preservatives/creosote predicted much higher ORs; exposure to pets comparable. Only logistic model statistically significant.
13 (1.2–360)	3	1	Hardell et al. [56]	2,4-D only	Chlorophenols. Potential for recall bias in questionnaires used for exposure. No dose response relationship observed. Forestry.
5.5 (2.7–11)	25	24	Hardell et al. [56]	Phenoxys (including 2,4-D, 2,4,5-T, and MCPA)	2,4,5-T known to contain dioxin. No dose response relationship observed.
2.7 (1.0–7.0)	12	11	Hardell and Eriksson [60]	Primarily MCPA	Greater than 30 year latency to achieve statistical significance.
1.3 (0.7–2.3)	43	62	Hardell and Eriksson [60]	2,4-D/2,4,5-T
2.81 (1.27–6.22)	21	9	Eriksson et al. [71]	MCPA only overall	Questionnaire on work history; questions on exposure to pesticides, organic solvents, and other chemicals.  Numbers of years, days per year, and approximate length of exposure per day. No job-exposure matrix could be developed. One full day of exposure constituted exposure.
3.76 (1.35–10.5)	15	5	Eriksson et al. [71]	MCPA < 32 days of use
1.66 (0.46–5.96)	6	4	Eriksson et al. [71]	MCPA > 32 days of use
2.04 (1.24–3.36)	47	26	Eriksson et al. [71]	Phenoxys overall
2.83 (1.47–5.47)	32	13	Eriksson et al. [71]	Phenoxys < 45 days of use
1.27 (0.59–2.70)	15	13	Eriksson et al. [71]	Phenoxys > 45 days of use
1.3 (0.8–2.1)	51	92	Pearce et al. [73]	Primarily 2,4,5-T; MCPA not mentioned	Fencing work; employment in meat works statistically significant. “Farming” assumed to represent chlorophenoxy exposures.
2.2 (1.2–4.1)	24	78	Hoar et al. [57]	2,4-D (overall, not stratified)	No dose response (see below).
2.7 (0.9–8.1)	6	17	Hoar et al. [57]	Use of 2,4-D 1-2 d/y (frequency)	Only overall analysis statistically significant; no dose response relationship. Many other exposures; use of hierarchical modeling by class (herbicides only, insecticides only, etc.). Detailed questionnaire; but elicited dates and frequency of use of any herbicide on each farm instead of dates and frequency for each specific herbicide.
1.6 (0.4–5.7)	4	16	Hoar et al. [57]	Use of 2,4-D 3–5 d/y (frequency)
1.9 (0.5–6.7)	4	16	Hoar et al. [57]	Use of 2,4-D 6–10 d/y (frequency)
3.0 (0.7–11.8)	4	9	Hoar et al. [57]	Use of 2,4-D 11–20 d/y (frequency)
7.6 (1.8–32.3)	5	6	Hoar et al. [57]	Use of 2,4-D > 21 d/y	Only overall analysis statistically significant; no dose response relationship. Many other exposures; use of hierarchical modeling by class (herbicides only, insecticides only, etc.). Detailed questionnaire; but elicited dates and frequency of use of any herbicide on each farm instead of dates and frequency for each specific herbicide.
1.3 (0.3–5.1)	3	16	Hoar et al. [57]	Use of 2,4-D 1–5 yrs (duration)
2.5 (0.9–6.8)	7	22	Hoar et al. [57]	Use of 2,4-D 6–15 yrs (duration)
3.9 (1.4–10.9)	8	15	Hoar et al. [57]	Use of 2,4-D 16–25 yrs (duration)
2.3 (0.7–6.8)	6	17	Hoar et al. [57]	Use of 2,4-D > 26 yr (duration)
1.5 (0.9–2.5)	43	98	Zahm et al. [61]	2,4-D	Lawn care professionals.
1.07 (0.8–1.4)	NR	NR	Woods et al. [66]	Phenoxys; other compounds	Increased risks found for DDT (1.82 (1.04-3.2)) and organic solvents (1.35 (1.06-1.7)). Exposure based on job description. No dose response observed for phenoxys.
0.68 (0.3–1.4)	181	196	Woods [65]	2,4-D	Small but significant excess risk observed for farmers (all chemicals). Exposure poorly defined.
0.71 (0.3–1.5)	181	196	Woods [65]	Any phenoxy
1.2 (0.9–1.6)	118	231	Cantor et al. [64]	Largely 2,4-D	Statistically significant OR > 1.5 for personal handling, mixing, or application of carbaryl, chlordane, dichlorodiphenyltrichloroethane, diazinon, dichlorvos, lindane, maialinoli, nicotine, and toxaphene.
0.5 (0.2–1.2)	6	79	Leiss and Savitz [69]	Yard treated in last three months of pregnancy	Exposure dichotomous never exposed versus ever exposed; actual products and durations not specified. Lymphomas considered as a category.
0.8 (0.3–1.8)	15	118	Leiss and Savitz [69]	Yard treated in the two years between birth and diagnosis
0.6 (0.4–1.0)	10	98	Leiss and Savitz [69]	Yard treated in the two years prior to diagnosis	Exposure dichotomous never exposed versus ever exposed; actual products and durations not specified. Lymphomas considered as a category.
1.25 (0.54–2.90)	19	85	Kogevinas et al. [59]	Phenoxys	Exposure evaluated for phenoxy herbicides and chlorophenols, polychlorinated dibenzodioxins and furans, raw materials, process chemicals, and chemicals used in the production of phenoxy herbicides.
0.88 (0.36–2.18)	15	76	Kogevinas et al. [59]	MCPA/MCPP	Three industrial hygienists carried out questionnaire-based analysis of exposure to 21 chemicals or mixtures. Nested case-control in IARC cohort [83].
1.11 (0.46–2.65)	12	56	Kogevinas et al. [59]	2,4-D/P/B	See previous/above
1.32 (1.01–1.73)	111	293	McDuffie et al. [13]	2,4-D	Small validation study of exposure questionnaire. Considered many covariates and exposures. Final models did not include MCPA or 2,4-D. Previous cancer and family history strong predictors.
1.10 (0.6–2.0)	17	46	McDuffie et al. [13]	MCPA
1.25 (0.96–1.62)	110	293	McDuffie et al. [62]	2,4-D	Cross-Canada study. Mecoprop exposures show strongest relationship; also DEET.
1.09 (0.6–1.98)	17	46	McDuffie et al. [62]	MCPA
1.09 (0.76–1.56)	64	186	McDuffie et al. [62]	2,4-D	Farm study. Mecoprop exposures show strongest relationship; also DEET.
0.98 (0.7–1.37)	15	33	McDuffie et al. [62]	MCPA
0.9 (0.6–1.2)	123	314	De Roos et al. [16]	2,4-D	Pooled data from three previous case-control studies.
0.9 (0.4–2.0)	8	16	De Roos et al. [16]	MCPA	Strongest associations for organophosphates, chlordane, and dieldrin.
1.0 (0.5–2.0)	18	NR	Miligi et al. [58]	Chlorophenoxys and men
1.3 (0.5–3.7)	11	NR	Miligi et al. [58]	Chlorophenoxys and women	Crop exposure matrix for exposure based on face-to-face interview questionnaire together with pesticide usage statistics by area.
0.7 (0.3–1.9)	6	NR	Miligi et al. [58]	2,4-D and men
1.5 (0.4–5.7)	7	NR	Miligi et al. [58]	2,4-D and women
1.1 (0.4–3.5)	8	NR	Miligi et al. [58]	MCPA and women
1.1 (0.6–1.8)	32	28	Miligi et al. [58]	Chlorophenoxys overall
2.4 (0.9–7.6)	13	6	Miligi et al. [58]	Chlorophenoxys without protective equipment
0.9 (0.5–1.8)	17	18	Miligi et al. [87]	2,4-D overall
4.4 (1.1–29.1)	9	3	Miligi et al. [87]	2,4-D without protective equipment
0.9 (0.4–1.8)	18	19	Miligi et al. [87]	MCPA overall	Crop exposure matrix for exposure based on face-to-face interview questionnaire together with pesticide usage statistics by area.
3.4 (0.8–23.2)	7	3	Miligi et al. [87]	MCPA without protective equipment
1.1 (0.78–1.55)	257	161	Hartge et al. [15]	500 ng/g 2,4-D in carpet dust
0.91 (0.45–1.45)	86	59	Hartge et al. [15]	500–999 ng/g 2,4-D in carpet dust	No dose response observed; residential exposures from tracking following yard application. Measured exposures but not concurrent.
0.66 (0.45–0.98)	165	162	Hartge et al. [15]	1000–9999 ng/g 2,4-D in carpet dust
0.82 (0.41–1.66)	24	18	Hartge et al. [15]	>10000 ng/g 2,4-D in carpet dust	See previous/above.
3.8 (1.85–7.81)	60	NR	Mills et al. [12]	2,4-D	US farmworkers union.
1.75 (0.42–7.38)	3	5	Fritschi et al. [67]	Chlorophenoxys
0.9 (0.4–1.9)	11	25	Orsi et al. [70]	Phenoxys
0.94 (0.67–1.33)	49	187	Hohenadel et al. [17]	2,4-D
1.78 (1.27–2.5)	63	133	Hohenadel et al. [17]	2+ phenoxys