Table 2.

Reviewed articles on chemical and biological hazards and leukemia

Researcher	Year	Type of study	Exposure	Main findings
1) Exposure to benzene
Zhang [49]	2007	Molecular epidemiological study	Exposure to benzene	A statistically significant increase % of genetic aberrations commonly observed in chemotherapy-related leukemias has been shown among workers exposed to benzene compared to non-exposed controls.
Richardson [50]	2009	Cohort study	Exposure to benzene	The observed pattern of leukemia mortality among rubber-production workers exposed to benzene, compared to the prediction of a TSCE statistical model suggests that benzene plays a role to the kinetics of cancer cells rather than the initial malignant transformation.
Rushton [51]	2010	Ecological study	Exposure to benzene	The Attributable Fraction (AF) of population mortality from acute non-lymphocytic leukemia related to occupational exposure to benzene was estimated at 0.25% (95% CI 0.0-4.65).
2) Exposure to organic solvents (incl. benzene)
Costantini et al. [52]	2008	Polycentric case-control study	Organic solvents	A significant increase of CLL risk has been shown among the groups of workers with moderate – high exposure to Benzene (OR 1.8, 95% CI 0.9-3.9), and high exposure to Xylene (OR 1.9, 95% CI 0.8-4.5) and Toluene (OR 2.1, 95% CI 0.9-4.7).
Cocco et al. [53]	2010	Case-control study	Organic solvents	A small but statistically significant increase of CLL risk (OR 1.3, 95% CI 1.1-1.6) was shown for workers ever exposed to organic solvents (exposure to any solvent or combined exposure of benzene with toluene, xylene or gasoline) compared to non-exposed.
Lehman et al. [54]	2006	Cohort study	Organic solvents	No statistically significant increase in mortality from leukemia was found among exposed workers in footwear industry, compared with the general population (SMR 1.01, 95% CI 0.67-1.48).
3) Exposure to Dioxins
Atallah et al. [55]	2007	Case-report	Dioxins – Agent Orange	A rare case of Acute Promyelocytic Leukemia (APL) in a former USAF pilot, who was involved in spraying Agent Orange during the Vietnam War, was reported.
Collins et al. [56]	2009	Cohort-study	TCDD	No significant increase of leukemia mortality was shown among exposed workers (SMR 1.9, 95% CI 1.0- 3.2). No significant association was shown between leukemia mortality and cumulative exposure (ppb) to TCDD (p=0.34).
4) Exposure to chemical compounds used in the synthetic rubber industry
Delzell et al. [57]	2006	Cohort-study	BD, DMDTC and Styrene	A positive association was shown between (all) leukemias, CML and CLL mortality and occupational exposure to BD. A positive association was also found between leukemia and exposure to Styrene or DMDTC, but in both cases there was also co-exposure to BD.
Beall et al. [58]	2007	Cohort-study	Solvents, aromatic amines	No increased leukemia incidence (SIR 0.68, 95% CI 0.14-1.98) or mortality (SMR 0.95, 95% CI 0.31- 2.23) has been observed among exposed workers, compared to the general population.
Cheng et al. [59]	2007	Cohort-study	BD	A statistically significant association was shown between leukemia risk and exposure to BD, for cumulative exposure in ppm-years (RR 3.84, 95% CI 1.51- 9. 76), frequency of exposure (RR 4.26, 95% CI 1.62-11.21) and average exposure in ppm (RR 3.93, 95% CI 1.5-10.32).
Sathiakumar et al. [60,61]	2009	Cohort-study	BD and Styrene	In contrast to the results observed among men workers, no statistically significant association was found between exposure of women workers to BD and mortality from leukemia (SMR 0.78, 95% CI 0.38-1.44).
5) Exposure to Formaldehyde
Beane Freeman [62]	2009	Cohort-study	Formaldehyde	A non-significant increase in mortality from (all) leukemias (RR 1.42, 95% CI 0.92- 2.18) and myeloid leukemia (RR 1.78, 95% 0.87- 3.64) was shown in the group with the highest exposure (> 4ppm) compared to the group with the lowest exposure.
Hauptmann [63]	2009	Case-control study	Formaldehyde	A statistically significant association between mortality from myeloid leukemia and increasing years of employment (p=0.02) or maximum exposure to formaldehyde (p=0.036) was shown among embalmers.
Zhang [64]	2010	Molecular epidemiological study	Formaldehyde	A statistically significant decrease of cell-lines, reduced activity of the CFU-GMs and increase of leukemia-related genetic aberrations has been shown among workers exposed to formaldehyde compared to non-exposed controls.
Speit [65]	2010	Letter to the editor	Formaldehyde	A number of methodological issues call into question the reliability of the findings of the study of Zhang et al, on in-vitro evidence of leukemia-specific chromosomal changes in workers exposed to formaldehyde.
6) Exposure to Lead
Lam [66]	2007	Cohort study	Occupational exposure to lead	A non-significant increase of CML incidence was shown (SIR 1.75, 95% CI 0.02- 9.71) among the cohort of workers exposed to lead (metal constructions, metal processing industry, foundries, manufacture of batteries and electronics, glass production).
7) Exposure to different types of pesticides, herbicides and insecticides
Mahajan [67]	2006	Cohort study - (AHS)	Organophosphate pesticide - Fonofos	A statistically significant increase of leukemia risk was found among pesticide applicators with the highest exposure (based on duration and intensity of exposure) compared to the non-exposed (RR 2.67, 95% CI 1.06-6.70).
Mahajan [68]	2006	Cohort study - (AHS)	Organophosphate pesticide - Phorate	The small number of recorded cases of leukemia among exposed workers did not allow for any reliable conclusions.
Miligi [69]	2006	Case-control study	Different groups of pesticides	No significant association with leukemia risk was shown for exposure to fungicides (OR 1.0, 95% CI 0.7 -1.3), herbicides (OR 1.4, 95% CI 0.8-2.3), insecticides (OR 1.0, 95% CI 0.7 -1.4), molluscicides (OR 0.9, 95% CI 0.3-2.5) or rodenticides (OR 0.4, 95% CI 0.1-1.2).
Hansen [70]	2007	Cohort study	Arsenate pesticides, Atrazine, Dichlorvos, Captafol, Amitrol, Lindane, DDT	A significant increase of leukemia incidence (SIR 2.33, 95% CI 1.32- 4.10) was found among the group of gardeners with high exposure to pesticides, previous to the 1960 restriction of the use of potentially carcinogenic substances.
Purdue [71]	2007	Cohort study - (AHS)	Organochlorine insecticides (Aldrin, Chlordane, DDT, Dieldrin, Heptachlor, Lindane, Toxaphene)	A marginal statistically significant association was found between the leukemia risk and previous use of any of the Organochlorine pesticides (RR 2.0, 95% CI 1.0-4.1), Lindane (RR 2.0, 95% CI 1.1-3.5) or Heptachlor (RR 2.1, 95% CI 1.1-3.9).
van Bemmel [72]	2008	Cohort study - (AHS)	Thio-carbamate herbicide EPTC	No statistically significant increase of leukemia risk was shown for workers exposed EPTC (RR 1.31, 95% CI 0.75-2.28) compared to the non-exposed.
Chrisman Jde [73]	2009	Ecological study	All pesticides	A statistically significant increase of leukemia mortality was observed in areas with increased per capita use of pesticides (MRR 1.6, 95% CI 1.55-1.66 and 1.93, 95% CI 1.87-2.0 for the 1st quartile of pesticide use, compared to the 2nd and 3rd quartile respectively).
Delancey [74]	2009	Cohort study - (AHS)	Herbicide Metribuzin	A statistically non-significant increase of leukemia risk was shown among the group of pesticide applicators with the highest cumulative exposure to Metribuzin (RR 2.42, 95% CI 0.82-7.19, p=0.08).
Orsi [75]	2009	Case-control study	Organochlorine insecticides, Phenoxy – herbicides, Triazine-containing herbicides	A significant association was shown between the risk of hairy cell leukemia (HCL) and exposure to Organochlorine insecticides (OR 4.9, 95% CI 1.1-21.2), Phenoxy-herbicides (OR 4.1, 95% CI 1.1-15.5) and Triazine-containing herbicides (OR 5.1, 95% CI 1.4-19.3).
Rusiecki [76]	2009	Cohort study - (AHS)	Exposure to Permethrin	No significant association was shown between exposure to Permethrin and leukemia risk among workers (RR 1.74, 95% CI 0.83 - 3.64 and 1.34, 95% CI 0.61-2.92 for workers with the longest duration of exposure or the highest cumulative exposure respectively).
8) Combined chemical and biological hazards in agriculture
Bassil [77]	2007	Literature review	Combined exposure to pesticides, insecticides and work with livestock	6 cohort studies and 8 case-control studies have shown a statistically significant association between pesticide exposure and leukemia risk, and 2 cohort studies have shown an association between leukemia risk and work with livestock.
9) Biological hazards in agriculture and food industry
Moore [78]	2007	Case-control study (multicentric)	Occupational exposure to meat products	A statistically significant association was found between CLL risk and occupational exposure to meat products, for workers with exposure> 16 years to cattle and poultry meat (OR 2.51, 95% CI 1.12 - 5.66 and 2.06, 95% CI 1.17 - 3.63 respectively).
Johnson [79]	2010	Cohort study	Occupational exposure to meat products	A statistically significant increase of lymphatic leukemia mortality was shown among men workers in slaughterhouses and poultry meat processing plants (SMR 5.9, 95% CI 1.6-15.2). No similar increase was found among female workers.
Johnson [80]	2010	Cohort study	Occupational exposure to meat products	A statistically significant increase of lymphatic leukemia proportional mortality was observed only among non-white women workers in slaughterhouses and poultry meat processing plants (PMR 6.4, 95% CI 1.3-31.1).