Occupational Exposure to Solvents and Risk of Non-Hodgkin Lymphoma in Connecticut Women

A population-based case-control study involving 601 incidentcases of non-Hodgkin lymphoma (NHL) and 717 controls was conductedin 1996–2000 among Connecticut women to examine associationswith exposure to organic solvents. A job-exposure matrix wasused to assess occupational exposures. Increased risk of NHLwas associated with occupational exposure to chlorinated solvents(odds ratio (OR) = 1.4, 95% confidence interval (CI): 1.1, 1.8)and carbon tetrachloride (OR = 2.3, 95% CI: 1.3, 4.0). Thoseever exposed to any organic solvent in work settings had a borderlineincreased risk of NHL (OR = 1.3, 95% CI: 1.0, 1.6); moreover,a significantly increased risk was observed for those with averageprobability of exposure to any organic solvent at medium-highlevel (OR = 1.5, 95% CI: 1.1, 1.9). A borderline increased riskwas also found for ever exposure to formaldehyde (OR = 1.3,95% CI: 1.0, 1.7) in work settings. Risk of NHL increased withincreasing average intensity (P = 0.01), average probability(P < 0.01), cumulative intensity (P = 0.01), and cumulativeprobability (P < 0.01) level of organic solvent and withaverage probability level (P = 0.02) and cumulative intensitylevel of chlorinated solvent (P = 0.02). Analyses by NHL subtypeshowed a risk pattern for diffuse large B-cell lymphoma similarto that for overall NHL, with stronger evidence of an associationwith benzene exposure. Results suggest an increased risk ofNHL associated with occupational exposure to organic solventsfor women. case-control studies; lymphoma, non-Hodgkin; risk factors; solvents     

Paternal occupational exposure around conception and spina bifida in offspring

A multi-center case-referent study was conducted on the relation between paternal occupational exposure and spina bifida in offspring. Cases were born between 1980 and 1992 in The Netherlands. Referents were recruited from hospitals and from the general population. Postal questionnaires were used to gather information on occupation and potential confounders. Through job-specific telephone interviews with 122 case fathers and 411 referent fathers, detailed exposure information was collected on specific tasks, the use of chemical or physical agents, frequency of exposure, and use of protective equipment. The study yielded statistically significant associations between spina bifida and low exposure to welding fumes (OR = 1.6, 95% CI: 1.0–2.6) and low exposure to UV radiation during welding (OR = 2.6, 95% CI: 1.2–5.6), and suggestive findings of an association between spina bifida and moderate or high exposure to cleaning agents, moderate or high pesticide exposure (OR = 1.7, 95% CI: 0.7–4.0), and stainless steel dust (OR = 2.0, 95% CI: 0.8–5.2). No associations were identified for other paternal occupational exposures, such as organic solvents. Am. J. Ind. Med. 32:283-291, 1997. © 1997 Wiley-Liss, Inc.     

Acute myeloid leukemia and clonal chromosome aberrations in relation to past exposure to organic solvents

OBJECTIVES: The effects of occupational and leisure-time exposures on the risk of acute myeloid leukemia (AML) were investigated with emphasis on clonal chromosome aberrations (CCA) and morphological subtypes. METHODS: Consecutively diagnosed cases of AML (N=333) and 1 population referent per case were retrospectively included in the study. Information on worktasks, companies, and leisure-time activities was obtained with telephone interviews. Exposure probability and intensity were assessed by occupational hygienists. Associations were evaluated with logistic regression. RESULTS: Exposure to organic solvents was associated with an increased risk of AML [low exposure: OR 1.5 (95% confidence interval (95% CI) 1.0-2.3, moderate-high exposure: OR 2.3 (95% CI 1.0-5.0)]. For exposure to solvents, but not to benzene, the OR was 1.2 (95% CI 0.69-2.0) for "low" and 2.7 (95% CI 1.0-7.3) for "moderate-high" exposure. The observed effects increased with intensity and duration of exposure. The estimated effects were higher for patients >60 years of age at the time of diagnosis. The effect of exposure to organic solvents was not differential with regard to morphology [except possibly erythroleukemia: OR 4.2, 95% CI 1.0-17 or the presence of CCA in general]. No increased risk for AML with complex CCA or with total or partial losses of chromosomes 5 or 7 were observed, but a higher risk was found for AML with trisomy 8 (OR 11, 95% CI 2.7-42) as the sole aberration. CONCLUSIONS: Exposure to organic solvents was associated with an increased risk of AML. This association was not due to benzene exposure alone and may be modified by age. Furthermore, specific associations with trisomy 8, and possibly also erythroleukemia, were suggested.     

Risk of specific birth defects in relation to chlorination and the amount of natural organic matter in the water supply

To assess the effect of water chlorination by-products on specific birth defects, the authors conducted a nationwide cross-sectional study of 285,631 Norwegian births in 1993-1998. Risks of birth defects according to four chlorination by-product exposure categories were compared on the basis of chlorination (yes/no) and level of water color (mg Pt/liter), representing the amount of natural organic matter: high (chlorination, < or =20), medium (chlorination, 10-19.9), and low (chlorination, <10) exposure, with no chlorination and low color (<10) as the reference category. In logistic regression analysis, the risks of any birth defect (adjusted odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.01, 1.25) and of cardiac (adjusted OR = 1.37, 95% CI: 1.00, 1.89), respiratory system (adjusted OR = 1.89, 95% CI: 1.00, 3.58), and urinary tract (adjusted OR = 1.46, 95% CI: 1.00, 2.13) defects were significantly associated with exposure (medium and high combined). Regarding risk of specific birth defects, only that for ventricular septal defects was significantly elevated, with an exposure-response pattern, yielding adjusted odds ratios of 1.63 (95% CI: 1.02, 2.58) for the medium and 1.81 (95% CI: 1.05, 3.09) for the high exposure categories. Furthermore, risk of neural tube defects was related to high color (adjusted OR = 2.60, 95% CI: 1.30, 5.26).     

Paternal laboratory work and congenital malformations

Animal studies indicate male-mediated teratogenicity for certain carcinogens/mutagens. Nevertheless, paternal occupational determinants of malformations in humans have been sparsely investigated. Data on male employees at Swedish universities from 1970 to 1989 were linked to the Medical Birth Register. The relationship between major malformations and exposure to laboratory work and to specific laboratory agents/techniques before the third trimester were analyzed using logistic regression. For major malformations, "laboratory work in general" (n = 3237) gave an adjusted odds ratio (OR) of 1.3 (95% CI = 0.8-2.1) and carcinogenic solvent use (n = 2489) of 2.0 (95% CI = 0.8-4.9) around the time of conception. For carcinogenic solvents and neural crest malformations, OR was 4.9 (95% CI =1.5-15.8). In conclusion, the prevalence of congenital malformations was not increased in offspring of males with laboratory work in general (1970-1989). Paternal work with agents such as carcinogens could, however, be of concern.     

Gender differences in risk of renal cell carcinoma and occupational exposures to chlorinated aliphatic hydrocarbons.

BACKGROUND: Organic solvents have been associated with renal cell cancer; however, the risk by gender and type of solvents is nuclear. METHODS: We evaluated the risk of renal cell carcinoma among men and women exposed to all organic solvents-combined, all chlorinated aliphatic hydrocarbons (CAHC)-combined, and nine individual CAHC using a priori job exposure matrices developed by NCI in a population-based case-control study in Minnesota, U.S. We interviewed 438 renal cell cancer cases (273 men and 165 women) and 687 controls (462 men and 225 women). RESULTS: Overall, 34% of male cases and 21% of female cases were exposed to organic solvents in general. The risk of renal cell carcinoma was significantly elevated among women exposed to all organic solvents combined (OR = 2.3; 95% CI = 1.3-4.2), to CAHC combined (OR = 2.1; 95% CI = 1.1-3.9), and to trichloroethylene (TCE) (OR = 2.0; 95% CI = 1.0-4.0). Among men, no significant excess risk was observed among men exposed to any of these nine individual CAHCs, all CAHCs-combined, or all organic solvents-combined. DISCUSSION: These observed gender differences in risk of renal cell carcinoma in relation to exposure to organic solvents may be explained by chance based on small numbers, or by the differences in body fat content, metabolic activity, the rate of elimination of xenobiotics from the body, or by differences in the level of exposure between men and women, even though they have the same job title.     

Paternal age and the risk of birth defects in Norway

PURPOSE: We studied 1,869,388 births from The Medical Birth Registry of Norway to assess the effect of father's age on risks of birth defects in offspring. METHOD: Thirteen separate categories were studied including pooled categories of neural tube defects and any type of defect. We used logistic regression models to adjust for maternal age, year of birth, maternity institution, parity, and correlation between siblings. RESULTS: There was little evidence of increased risk by high paternal age for any category of defects, except for a category of "other central nervous system" where risk estimates were 2.5-fold (95% CI: 1.2-5.5) for fathers aged between 45 and 49 years compared with the reference age group (25-29 years). The risk for neural tube defects was 1.3-fold (95% CI: 1.1-1.5) when the father was aged between 20 and 24 years relative to the reference. A pattern of moderately higher risks for younger fathers was consistent for anencephaly and spina bifida. Increased risk of heart defects was also estimated among children of young fathers. CONCLUSIONS: This study does not show consistent evidence that paternal ageing is a risk for birth defects among offspring. Low paternal age, or factors associated with younger parents, may however be associated with increased risk of neural tube defects in their offspring.     

Pregnancy outcome among offspring of airline pilots and cabin attendants

OBJECTIVES: This study assessed the occurrence of perinatal death, low birthweight, preterm birth, and birth defects (total, major, neural tube defects, total cleft, cleft palate, hypospadias, and Down syndrome) in the offspring of airline pilots and cabin attendants. METHODS: A cohort of offspring of airline pilots and cabin attendants was established and characterized in terms of parental exposure to cosmic radiation the year before birth or ever. Pregnancy outcome was derived from the Medical Birth Register of Norway. The reference group comprised offspring of parents without occupational exposure to cosmic radiation. RESULTS: No deviant risks were observed for the offspring of male pilots, either for the year preceding birth (N=2,111) or ever (N=2,356). Specific birth outcomes were fewer for the pilots than for the referents (N=1,621,186), except for Down syndrome, which was more frequent [odds ratio (OR) 1.41, 95% confidence interval (95% CI) 0.53-3.76]. For exposure the year preceding birth (N=2,512), the risk of low birthweight was lower for the female cabin attendants than for the referents (adjusted OR 0.83, 95% CI 0.69-1.00), while Down syndrome was more frequent (OR 1.44, 95% CI 0.60-3.47). For exposure ever (N=3346), the risk of low birthweight was lower (OR 0.82, 95% CI 0.70-0.96) for the cabin attendants, while hypospadias (OR 1.18, 95% CI 0.61-3.04) and Down syndrome (OR 1.79, 95% CI 0.03-3.45) were more frequent CONCLUSIONS: In general, offspring of air pilots and cabin attendants do not seem to be at increased risk of adverse pregnancy outcome.     

Genetic polymorphism of metabolic enzymes modifies the risk of chronic solvent-induced encephalopathy

In the present study, we investigate whether genetic polymorphism in enzymes involved in the metabolism of organic solvents influences susceptibility to chronic solvent encephalopathy (CSE), which is one of the major effects of long-term exposure to organic solvents. Polymorphisms in the genes encoding CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1 and GSTP1 enzymes were determined in a group of male CSE patients (N=97) and controls (N=214). The selection of the patients was based on a standard diagnostic protocol, including interviews, neuropsychological tests and questionnaires directed to somatic, cognitive and mood symptoms and exposure, in combination with well-defined decision rules. As controls, healthy workers of similar socio-economic background, without memory problems and with no known exposure to organic solvents, were included in the study. Comparing patients and controls, higher frequencies of the variant *5B allele of the CYP2E1 gene (OR: 5.8; 95% CI: 1.8-18.8) and of the variant GSTP1*C allele (OR: 0.40; 95% CI: 0.17-0.94) were found. Homozygous carriers of the exon 4 EPHX1 Arg139 variant allele had a lower risk (OR: 0.25; 95% CI: 0.06-1.13). The present study indicates that genetic polymorphism of CYP2E1, EPHX1 and GSTP1 modify the risk of developing CSE.     

Effects of hyperinsulinemia and obesity on risk of neural tube defects among Mexican Americans.

Although both maternal obesity and diabetes mellitus increase the risk for neural tube defects, it is unknown whether they are independent risk factors or manifestations of an underlying prediabetic state such as hyperinsulinemia. We investigated whether hyperinsulinemia was a risk factor for neural tube defects independent of obesity and hyperglycemia in Mexican-American women. We identified case and control women from residents delivering or terminating pregnancies in hospitals or birthing centers in any of the 14 Texas-Mexico border counties during 1995-2000. Case women had a pregnancy affected by anencephaly, spina bifida, or encephalocele; randomly selected control women had normal births, frequency matched by year and birth facility. Questionnaire and laboratory values obtained 5-6 weeks postpartum were available for 149 case and 178 control women. Both hyperinsulinemia and obesity were related to increased neural tube defect risk [odds ratio (OR) = 1.91, 95% confidence interval (CI) = 1.21-3.01 and OR = 1.73, 95% CI = 1.03-2.92, respectively]. Adjustment for obesity only slightly reduced the effect of hyperinsulinemia (OR = 1.75, 95% CI = 1.09-2.82). Alternatively, a modest effect remained for obesity after adjustment for hyperinsulinemia (OR = 1.45, 95% CI = 0.84-2.51). Hyperinsulinemia is a strong risk factor for neural tube defects and may be the driving force for the observed risk in obese women.     

Maternal exposure to occupational solvents and childhood leukemia

Many organic solvents are considered probable carcinogens. We carried out a population-based case-control study including 790 incident cases of childhood acute lymphoblastic leukemia and as many healthy controls, matched on age and sex. Maternal occupational exposure to solvents before and during pregnancy was estimated using the expert method, which involves chemists coding each individual's job for specific contaminants. Home exposure to solvents was also evaluated. The frequency of exposure to specific agents or mixtures was generally low. Results were generally similar for the period ranging from 2 years before pregnancy up to birth and for the pregnancy period alone. For the former period, the odds ratio (OR), adjusted for maternal age and sex, for any exposure to all solvents together was 1.11 [95% confidence interval (CI), 0.88-1.40]. Increased risks were observed for specific exposures, such as to 1,1,1-trichloroethane (OR = 7.55; 95% CI, 0.92-61.97), toluene (OR = 1.88; 95% CI, 1.01-3.47), and mineral spirits (OR = 1.82; 95% CI, 1.05-3.14). There were stronger indications of moderately increased risks associated with exposure to alkanes (C5-C17; OR = 1.78; 95% CI, 1.11-2.86) and mononuclear aromatic hydrocarbons (OR = 1.64; 95% CI, 1.12-2.41). Risk did not increase with increasing exposure, except for alkanes, where a significant trend (p = 0.04) was observed. Home exposure was not associated with increased risk. Using an elaborate exposure coding method, this study shows that maternal exposure to solvents in the workplace does not seem to play a major role in childhood leukemia.     

Extended mortality follow-up of a cohort of dry cleaners

PURPOSE: The mortality follow-up of a cohort of dry cleaners was extended to further evaluate cancers risks associated with organic solvents. METHODS: The underlying and contributing causes of death among 5,369 members of a dry cleaning union in St. Louis were determined through December 31, 1993. The mortality experience of the cohort was compared to that of the US population adjusted for age at entry, year of death, race and gender. RESULTS: The total mortality was about as expected (SMR = 1.0, N = 2351, 95% CI = 1.0-1.1). Excesses were observed for emphysema (SMR = 1.7, N = 21, 95% CI = 1.0-2.5), Hodgkin's disease (SMR = 2.0, N = 5, 95% CI = 0.6-4.6) and cancers of the esophagus (SMR = 2.2, N = 26, 95% CI = 1.5-3.3), larynx (SMR = 1.7, N = 6, 95% CI = 0.6-3.7), lung (SMR = 1.4, N = 125), 95% CI = 1.1-1.6), and cervix (SMR = 1.6, N = 27, 95% CI = 1.0-2.3). These excesses occurred among men and women and blacks and whites. Bladder cancer was elevated among white men and women and kidney cancer among black men and women, but not significantly so. None of these causes of death showed strong relationships with duration or estimated level of exposure to dry cleaning solvents, although relative risks for cancers of the larynx, lung and kidney were larger among subjects estimated to have higher levels of exposure and risks from bladder cancer and chronic nephritis were greater among persons who entered the union after 1960. CONCLUSION: The excesses observed are unlikely to be due to chance because most occurred in earlier as well as the recent follow-up. The specific factors contributing the excesses, however, are not clear. Socioeconomic, lifestyle, and occupational exposures are all possibilities. Lack of information on socioeconomic and lifestyle factors hampers evaluation.     

Parental exposure to organic solvents and reduced birth weight

The authors investigated the association of birth weight with maternal and paternal exposure to organic solvents in 1,222 couples employed in a large petrochemical corporation in Beijing, China, during the period between 1994 and 1998. A trained interviewer assessed parental exposures to organic solvents. The authors used generalized additive models to examine the association between birth weight and parental exposure to organic solvents. After the authors adjusted for potential confounders, maternal exposure to solvents was significantly associated with reduced birth weight (-81.7 gm, 95% confidence interval = -106.3, -3.1), and reduced birth weights of female babies and of younger mothers' babies were statistically significant. Maternal exposure to organic solvents was associated with reduced birth weight in this population, but paternal exposure to organic solvents was not similarly associated.     

Indicators of mancozeb exposure in relation to thyroid cancer and neural tube defects in farmers' families

OBJECTIVES: The fungicide mancozeb has been suspected of causing thyroid cancer and neural tube defects. The aim of the study was to investigate associations of indicators of mancozeb exposure with thyroid cancer and neural tube defects in farmers' families. METHODS: National registers in Norway, identifying 105 403 female and 131 243 male farmers, born in 1925-1971, and their 300 805 children available for analyses, born in 1952-1991, were cross-linked with national agricultural censuses, 1969-1989, and the population register. Neural tube defects (ICD-8 740-742) at birth among the 102 703 children conceived between May 1973 and April 1991 were identified in the medical birth register. Likewise thyroid cancer (ICD-7 194) was identified in the cancer register through 2000. Data on farm production and fungal forecasts (humid and temperate weather conditions) in 1973-1990, obtained from agricultural censuses and meteorological measurement stations, respectively, served as the mancozeb exposure indicators. The adjusted rate ratio or prevalence ratio (PR) estimates with 95% confidence intervals (95% CI) were computed in a Poisson regression analysis. RESULTS: Neural tube defects (131 cases, prevalence 12.8/10 000 births) was moderately associated with potato cultivation (PR 1.6, 95% CI 1.1-2.3) and paternal work of > 500 hours/year (PR 1.6, 95% CI 1.1-2.5). Altogether 319 thyroid cancer cases were identified: 141 in female farmers (incidence 10.2/100 000 person-years), 79 in male farmers (incidence 3.2/100 000 person-years), and 99 in offspring (female and male incidence 3.4 and 0.6/100 000 person-years, respectively). Mancozeb exposure was not associated with thyroid cancer. CONCLUSIONS: A moderate association seems to exist between mancozeb exposure and neural tube defects, but not between mancozeb exposure and thyroid cancer.     

Neural tube defects and drinking water disinfection by-products.

We conducted a population-based case control study of neural tube defects and drinking water contaminants, specifically, disinfection by-products. We used public monitoring records concurrent with the first month of gestation to assess exposure. The prevalence odds ratios (PORs) for the highest tertile of total trihalomethanes compared with the lowest was 1.6 (95% confidence interval [CI] = 0.9-2.70). Surface water source was also associated with neural tube defects (POR = 1.5; 95% CI = 0.9-2.5). Sensitivity analyses restricted to isolated neural tube defect cases and mothers with known residence at conception yielded stronger associations [total trihalomethanes, POR = 2.1 (95% CI = 1.1-4.0); surface water, POR = 1.7 (95% CI = 0.9-3.2)]. Other major groups of disinfection by-products (haloacetic acids and haloacetonitriles) showed little relation to these defects.     

Pregnancy outcome following maternal organic solvent exposure: A meta-analysis of epidemiologic studies

Background Evidence of fetal damage or demise from occupational organic solvent levels that are not toxic to the pregnant woman is inconsistent in the medical literature. The risk for major malformations and spontaneous abortion from maternal inhalation of organic solvent exposure during pregnancy was summarized using meta-analysis. Methods Medline, Toxline, and Dissertation Abstracts databases were searched to locate all research papers published in any language from 1966 to 1994. Included were studies that were case-control or cohort in design and indicated first trimester (or up to 20 weeks gestation for spontaneous abortion) maternal solvent exposure. A summary odds ratio (ORs) with 95% confidence intervals (CI) was calculated from research results combined by the Mantel-Haenszel method. Results In total, 559 studies were obtained from the literature search. Five studies for each outcome of interest qualified for inclusion in the analysis. The ORs for major malformations from five studies (n = 7,036 patients) was 1.64 (CI 1.16–2.30) and for spontaneous abortion from five studies (n = 2,899 patients) was 1.25 (CI 0.99–1.58). Conclusions Maternal occupational exposure to organic solvents is associated with a tendency toward an increased risk for spontaneous abortion and additional studies may affect the trend. There is a statistically significant association with major malformations which warrants further investigation. Am. J. Ind. Med. 34:288–292, 1998. © 1998 Wiley-Liss, Inc.     

Parental Exposure to Organic Solvents and Reduced Birth Weight

The authors investigated the association of birth weight with maternal and paternal exposure to organic solvents in 1,222 couples employed in a large petrochemical corporation in Beijing, China, during the period between 1994 and 1998. A trained interviewer assessed parental exposures to organic solvents. The authors used generalized additive models to examine the association between birth weight and parental exposure to organic solvents. After the authors adjusted for potential confounders, maternal exposure to solvents was significantly associated with reduced birth weight (-81.7 gm, 95% confidence interval = ?106.3, ?3.1), and reduced birth weights of female babies and of younger mothers' babies were statistically significant. Maternal exposure to organic solvents was associated with reduced birth weight in this population, but paternal exposure to organic solvents was not similarly associated.     

Occupational risk factors for renal cell cancer. An Italian case-control study

AIM: To examine possible associations between occupational and environmental risk factors and renal cell cancer (RCC), a tumour with unclear aetiology and increasing incidence. METHODS: A questionnaire-based case-control study of 100 histologically verified cases of RCC and 200 controls was conducted at Parma University Hospital. The control group was enrolled from patients attending different outpatient departments and represented the same residential area as the cases. For all exposure variables under study, two levels of duration were defined: "short" and "prolonged" for less than 10 years or more, respectively. RESULTS: The highest risk estimates for RCC were found for "prolonged" exposure to organic solvents with an odds ratio (OR) of 2.2 (95% confidence interval, CI: 1.0-4.8). "Prolonged" exposures to pesticides and copper sulphate were also associated with increased risk, OR 2.0 (95% CI: 0.8-4.7) and OR 2.7 (95% CI: 1.3-5.5), respectively. CONCLUSIONS: Our data suggests an association between RCC and exposure to organic solvents, pesticides and copper sulphate. A risk gradient as a function of exposure duration was found for organic solvents (p = 0.044) and copper sulphate (p = 0.036), but not for pesticides.