Retrospective evaluation of the exposure to polycyclic aromatic hydrocarbons: comparative assessments with a job exposure matrix and by experts in industrial hygiene.

This work aimed at assessing the validity of job exposure matrix (JEM) for the retrospective evaluation of exposure to polycyclic aromatic hydrocarbons (PAH) within the framework of population-based case-control studies, taking the evaluation of industrial hygiene experts as reference. For this purpose, we used a case-control study for which the different levels of exposure were assessed by such experts after case by case evaluation of all job periods reported by the subjects. The JEM was applied to this set of data so that we had, according to job periods, the experts' evaluation on the one hand, and the JEM evaluation on the other. JEM sensitivity and specificity of the matrix vary widely from 0.13 to 0.96 and 0.58 to 0.99 respectively, depending on whether the experts chose a narrow or wide definition of exposure and on the cutoff point chosen to dichotomize the JEM. We also computed, according to the sensitivity and specificity of the JEM, the odds ratio (OR) and relative efficiency (RE) given by the JEM for several hypothetical OR and frequencies of exposure among the controls. These calculations were made for different definitions of exposure by the experts and different cutoff points for the JEM. The results show a bias in the JEM's evaluation of the OR. In addition, the RE varies widely from very low values to high values (0.05-0.45) depending on the experts' definition of exposure and the cutoff point chosen for the matrix. Note, however, that all these calculations were made taking the experts' evaluation as the reference.(ABSTRACT TRUNCATED AT 250 WORDS)

Occupational exposure to polycyclic aromatic hydrocarbons and the risk of bladder cancer: a French case-control study.

BACKGROUND: The risk of bladder cancer has been shown to be increased in occupations which are likely to involve exposure to polycyclic aromatic hydrocarbons (PAH), but up to now, most studies have considered this exposure in terms of job title. METHODS: A hospital-based case-control study of 658 male cases of bladder cancer and 658 male controls was carried out in five areas of France from 1984 to 1987. For each subject, occupational exposure to PAH was assessed from questionnaires by an expert according to a semi-quantitative index of exposure. RESULTS: The overall odds ratio for PAH exposure, adjusted for smoking, coffee drinking and occupational exposure to aromatic amines was estimated at 1.3 (95% CI: 1.0-1.7, P < 0.05). A slight but clear dose-response relationship was observed, and the trend remained significant after adjustment for cumulative smoking, with odds ratios of 1.2 (95% CI: 0.9-1.7), 1.4 (95% CI: 0.9-2.2) and 1.8 (95% CI: 0.8-3.9) for low, medium and high average exposures respectively compared to subjects unexposed to PAH (P for trend < 0.05). Moreover, the association between bladder cancer and PAH exposure was also investigated in a category of smokers homogeneous with respect to their tobacco consumption. In this heavy-smoker group, a stronger association with PAH was detected. CONCLUSIONS: These results support the hypothesis of a causal relationship between occupational exposure to PAH and bladder cancer risk.

Occupational risks of bladder cancer in France: a multicentre case-control study.

The relationships between occupational risk factors in France and bladder cancer were assessed from a hospital-based case-control study conducted between 1984 and 1987 in five regions representing various industries, including mining, textile manufacture, metallurgy and the production of rubber and chemicals. The study concerned 765 cases (658 men and 107 women) and the same number of controls. Odds ratios (OR) adjusted for matching variables (age, place of residence and hospital), and tobacco smoking were estimated by unconditional logistic regression. A significantly increased risk of bladder cancer was observed among men employed in coal mining (OR = 2.42; 95% confidence interval (Cl) : 1.25-4.67) and the chemicals industry (OR = 2.36; 95% Cl : 1.23-4.53). Aircraft and ship's officers (OR = 11.8; 95% Cl : 1.46-95.7), managers (OR = 1.64; 95% Cl : 1.11-2.43) and street vendors (OR = 3.60; 95% Cl : 1.15-11.3) also had an increased risk. Among women, employment in the clothing industry was associated with a high OR (= 3.21; 95% Cl : 1.34-7.71). Assessment of individual exposures by a panel of industrial hygiene experts showed that significantly more cases than controls had been exposed to the following substances: chlorinated solvents (OR = 1.86; 95% Cl : 1.19-2.90), industrial oils and greases (OR = 1.44; 95% Cl : 1.10-1.89), welding fumes (OR = 1.40; 95% Cl : 0.98-2.01), coal dust (OR = 1.71; 95% Cl : 1.02-2.89) and metallic oxide dust (OR = 2.99; 95% Cl : 1.12-8.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between birthweight and occupational exposure to cytostatic drugs during or before pregnancy.

The birthweight of babies whose mothers were exposed to cytostatic drugs during pregnancy was compared with that of infants whose mothers were not so exposed. The study was conducted in four French hospitals and covered 420 singleton live births to 466 women. One hundred and seven of the 420 births were exposed before or during pregnancy; 298 were not. Information about exposure was not available for the other 15. The mean birthweight of the babies of exposed mothers was 85 g lower than that of infants of unexposed mothers, but the difference was not statistically significant (95% CI -192.2-22.2 g). When gestational age and conventional risk factors were taken into account, the adjusted difference in the means of the birthweights was -56 (95% CI -155.1-43.1) g.

Farming, pesticide use and hairy-cell leukemia.

OBJECTIVES: This paper analyzes the role of farming and pesticide exposures in the occurrence of hairy-cell leukemia (HCL). METHODS: The study included 226 men with HCL and 425 matched hospital referents. Pesticide exposure was assessed by expert review of detailed interview data on occupational histories and agricultural activities and exposures. RESULTS: Altogether, 77 cases and 116 referents had farmed for at least six months, giving an odds ratio (OR) of 1.5 [95% confidence interval (95% CI) 1.0-2.2]. Forage growing was reported by 20.8% of the cases and 11.1% of the referents and was associated with HCL (OR 2.8, 95% CI 1.6-4.9), even among farmers who had never handled pesticides (OR 3.4, 95% CI 1.0-11.0). A significant association was found between HCL and pesticide use, the overall odds ratios for insecticide, fungicide, and herbicide use ranging from 1.5 to 2.4. Organophosphorus insecticides were the only agrochemicals with a positive association with HCL after other pesticide exposures, smoking, and forage growing were accounted for. A clear-cut negative interaction was found between smoking and exposure to organophosphorus insecticides. A multivariate analysis yielded odds ratio estimates of 2.8 (95% CI 1.4-5.6) for exposure to forage and 7.5 (95% CI 0.9-61.5) for nonsmokers exposed to organophosphorus insecticides. CONCLUSIONS: The present study argues for a role of organophosphorus insecticides in HCL among nonsmoking farmers and shows an unexpected association with forage growing. No evidence of an association with phenoxyacetic acids, triazines, or organochlorine insecticides was found.

Cancer risk among workers in biomedical research.

OBJECTIVE: This epidemiologic study was undertaken after a cluster of five cases of rare forms of cancer (bone sarcoma, non-Hodgkin's lymphoma) had been observed among biomedical research workers at the Pasteur Institute in Paris to ascertain whether their disease was connected with exposure during this research. METHODS: A mortality study included 3765 people who worked at the Pasteur Institute between 1971 and 1986 and were followed until the end of 1987. Within this cohort a nested case-referent study included 23 cases of cancer [non-Hodgkin's lymphoma (6), multiple myeloma (1), leukemia (3), pancreatic cancer (7), bone cancer (3), brain tumor (3)], and four referents per case, matched for gender and year of birth. RESULTS: Total mortality from cancer was less than expected, the standardized mortality ratio (SMR) being 72 for the men and 82 for the women. Among the women the proportion of pancreatic cancer cases was larger than expected [SMR 490, 95% confidence interval (95% CI) 158-1144], as was the number of brain cancer cases (SMR 239, 95% CI 48-696). Among the men, mortality from bone cancer was greater than expected (SMR 553, 95% CI 62-2006). In the nested case-referent study, more cases than referents had worked in the areas of molecular biology [odds ratio (OR) 7.1, 95% CI 1.5-33] and microbial genetics (OR 6.7, 95% CI 1.3-35). These cases especially included non-Hodgkin's lymphoma and bone cancer. Associated with this finding was the fact that more cases had used certain chemicals, including ethidium bromide, acrylamide, methylnitronitrosoguanidine and ethylmethanesulfonate, and radioactive compounds (essentially 32phosphorus). CONCLUSIONS: As the products used are potent genotoxicants, the present findings suggest that work in biomedical research might well involve an increased risk of certain types of cancer; this conclusion should be balanced by the fact that two of the five index cases were included in the mortality study and four in the nested case-referent study.

[Longitudinal study of radiologic anomalies in subjects working in asbestos-insulated buildings]. / Etude longitudinale des anomalies radiologiques chez des sujets travaillant dans des locaux floqués à l'amiante.

The respiratory effects of environmental pollution by asbestos was examined in a cohort of subjects working inside university buildings partly insulated with asbestos containing materials (University of Jussieu in Paris). The present study concerned 727 subjects having undergone two standard radiographic examinations (postero-anterior and oblique chest x-ray) in the period 1981-1992. The first examination was realized between 01/01/81 and 31/12/85 and the second examination took place between 01/01/86 and 31/12/92. The subjects were classified into three groups according to their exposure status: the group G1 consisted of 161 workers occupationally exposed to asbestos; the group G2 comprised 416 subjects working for at least 15 yr in asbestos-insulated buildings without known occupational exposure to asbestos; the group G3 consisted of 150 workers working for at least 15 yr in the university with no known exposure to asbestos. Whatever the radiological abnormalities considered, no significant difference was observed between G2 and G3 in cross-sectional analyses of the two phases. The group G1 exhibited a significantly higher prevalence of pleural thickening compared to the other exposure groups after adjustment for confounding variables. Detailed examination of oblique x-ray allowed to confirm that pleural thickening were largely due to extrapleural fat. Concerning the changes in pleural abnormalities between the two phases of the study, no difference was observed between G2 and G3. This study was unable to show any excess of radiographic chest abnormalities among subjects working in asbestos-insulated buildings compared to non-exposed subjects. However, the participation in the second phase of examination was 51.2%. The study is still on-going. Therefore, it would be necessary to continue to follow-up the subjects because respiratory disorders could occur after a long latent period.

Mercury exposure in French Guiana: levels and determinants.

Mercury is used widely for gold extraction in French Guiana and throughout the entire Amazon basin. To evaluate contamination among the general population, the authors chose individuals who attended 13 health centers and maternity hospitals dispersed geographically across the territory and served Guiana's different populations. Five hundred individuals (109 pregnant women, 255 "other" adults, and 136 children) who received care at one of the centers were selected randomly for this study. Each individual answered a questionnaire and provided a hair sample. The authors determined mercury in hair with atomic absorption spectrometry. The following mean levels of mercury were observed: 1.6 microg/g (95% confidence interval [CI]=1.3, 1.9) among pregnant women; 3.4 microg/g (95% CI=3.0, 3.9) among other adults; and 2.5 microg/g (95% CI=2.1, 3.0) among children. Diet factors contributed the most to mercury levels, especially consumption of freshwater fish (mean=6.7 microg/g for individuals who ate fish more than 5 times/wk) and livers from game. Other factors, including age, dental amalgams, use of skin-lightening cosmetics, and residence near a gold-mining community, did not contribute significantly to mercury levels. Overall, 12% of the samples contained mercury levels in excess of 10 microg/g, but in some Amerindian communities up to 79% of the children had hair mercury levels that exceeded 10 microg/g. The results of this study indicated that (a) diet played a predominant role in total mercury burden, and (b) in some communities, mercury contamination exceeded safe levels.

Work-related factors associated with age at natural menopause in a generation of French gainfully employed women.

This study's purpose was to identify occupational factors that may influence the age at natural menopause in a random sample of gainfully employed French women born in 1938 (n=1,594). Occupational physicians selected the subjects from their files and interviewed them during their annual visits in 1990 and 1995. The authors used Kaplan-Meier survival curves to estimate median age at menopause (52 years) and multiple Cox models to estimate associations among women's characteristics, occupational factors, and age at menopause separately within two strata distinguished by a self-reported history of depression. Among women without such a history, earlier menopause was associated with smoking more than 10 cigarettes per day in 1990 (p<0.001), a high-strain job (p=0.01) in 1990, and difficult schedules before 1990 (p=0.03). Later menopause was associated with higher educational status (p=0.003) and repetitive work in 1990 (p=0.005). Among women with a history of depression, a later menopause was associated with having at least one child (p<0.001) and menarche later than the age of 13 years (p=0.004). Earlier menopause was associated with a high job control in 1990 (p=0.03) and high school education (p<0.01). These results suggest that certain physical job stressors may be related to age at menopause.

Paternal exposure to mercury and spontaneous abortions.

The potential reproductive toxicity of mercury vapour was investigated by comparing the rate of spontaneous abortions among the wives of 152 workers occupationally exposed to mercury vapour with the rate among the wives of 374 controls in the same plant. The results indicate an increase in the rate of spontaneous abortions with an increasing concentration of mercury in the fathers' urine before pregnancy. At concentrations above 50 micrograms/l the risk of spontaneous abortion doubles (odds ratio (OR) = 2.26; 95% confidence interval (95% CI) = 0.99-5.23). Special care was taken to avoid bias in reporting abortions and known risk factors of spontaneous abortions do not seem to explain the results. Several biological mechanisms might account for them including, in particular, direct action of mercury on the paternal reproductive system and indirect toxicity to the mother or embryo through transport of mercury from the father. These indications could be of practical importance and should therefore be further documented.

Lead-exposed workmen and fertility: a cohort study on 354 subjects.

A cohort study was conducted in a French battery factory in 1977-1982 to explore the relationship between occupational lead exposure and fertility. A total of 354 battery workers, divided into 229 lead-exposed subjects (corresponding with 886 person-years) and 125 non-lead-exposed subjects (corresponding with 598 person-years) were compared, in a person-year analysis, for the risk of infertility. Lead exposure, at any level of absorption, did not appear significantly associated with a reduction in fertility after controlling for potential confounders: age, French origin, educational level, number of children at start of the period, cigarette smoking and exposure to heat. The apparent inconsistency between our results and those of several studies involving biological data and semen analysis is partially explained by recent knowledge relating to predictive value on the pregnancy of semen abnormalities.

Hematological findings among styrene-exposed workers in the reinforced plastics industry.

A cross-sectional survey of hematological parameters was carried out among 221 workers exposed to styrene in the reinforced plastics industry and 104 controls. Styrene exposure was assessed in both groups by monitoring urinary excretion of styrene metabolites (i.e. mandelic and phenylglyoxylic acids) in post-shift urinary samples collected over five consecutive days. Blood tests were performed with the same counter for all subjects. Information on factors liable to affect hematological parameters was collected from personal questionnaires completed by the workers. Urinary excretion of styrene metabolites varied from 15 to 3740 mg/g creatinine. Exposed subjects exhibited significantly lower mean values of neutrophils and mean corpuscular hemoglobin concentration (MCHC) than controls, and significantly higher mean values for monocytes and mean corpuscular volume. A dose-effect relationship was found for MCHC which decreased with urinary metabolite concentrations. These results remained statistically significant for all parameters after adjustment for age, sex, tobacco and alcohol consumption, place of residence (rural or urban) and time of blood sampling (morning or afternoon) with the exception of neutrophils whose relationship with exposure was essentially explained by smoking. These results are suggestive of a direct effect of styrene-exposure--in the range considered--on the statistical distribution of some hematological parameters.

Incidence and risk factors for childhood brain tumors in the Ile de France.

A case-control study investigating risk factors for childhood brain tumors was conducted in the Ile de France (Paris region). During a 2-year period (1985-1987) 109 newly diagnosed cases were identified and, of these, 75 could be interviewed. In the same region, 113 population controls, frequency-matched for year of birth, were interviewed. Odds ratios adjusted for child's age and sex and for maternal age were estimated for each risk factor present in utero or during childhood by conditional logistic regression. Statistically significant associations were found for the following risk factors: farm residence, cat scratches, home treated with pesticides, passive smoking, family history of cancer, antihistamine intake. Intake of vitamin supplements during childhood was associated with a decrease in risk. This study is part of a multicentric case-control study coordinated by the International Agency for Research on Cancer and its results will be compared for consistency, and pooled with those of other centers using the same protocol.

Occupational paternal exposure to benzene and risk of spontaneous abortion.

OBJECTIVE: The purpose of this study was to evaluate the risk of spontaneous abortion among the wives of male workers occupationally exposed to benzene. METHODS: The wives of 823 men working in two chemical plants at the time of the study were asked to complete a questionnaire describing their pregnancies. The analysis of the 1739 pregnancies that ended in a spontaneous abortion or a birth is presented. The firms' payroll records provided all workers' employment history, including dates. Benzene exposure, graded at two levels (< 5, > or = 5 ppm), was determined for every job, so that benzene exposure for each worker's entire professional life (at these companies) could be assessed. This information was linked to the dates of the pregnancies reported in the questionnaires to enable the exposure status of each pregnancy to be defined (1270 non-exposed and 274 exposed). The frequency of spontaneous abortion, defined as the number of spontaneous abortions divided by the total of spontaneous abortions and births was evaluated. RESULTS: When adjusted for tobacco consumption, mother's age and pregnancy order, the odds ratio of the association between paternal exposure to approximately 5 ppm of benzene and the risk of spontaneous abortion was close to and statistically not different from unity (OR = 1.1; 95% CI (0.7-1.8). CONCLUSION: In this study paternal exposure to benzene did not increase the risk of spontaneous abortion.

Hairy cell leukaemia, occupation, and smoking.

The roles of farm practices, occupational exposures to organic solvents, and ionizing radiation in the risk of hairy cell leukaemia (HCL) were examined in a French hospital-based multicentre case-control study including 291 cases (229 men and 62 women) and 541 controls (425 men and 116 women). No positive association was observed with occupations involving exposure to organic solvents or with self-declared exposures to solvents, but a significant association with self-reported exposure to petrol or diesel was found for men (OR = 1.5 CI95% [1.0-2.1]). No association with ionizing radiation was detected. Agriculture employment gave an odds ratio of 1.7 (CI95% [1.1-2.4]) for men and 2.7 (CI95% [1.1-6.7]) for women. Among men, the association seems to affect farmers rather than agricultural workers. Self-declared exposure to pesticides or bovine cattle breeding was related to HCL risk in both genders. Finally, a significant negative association with smoking was observed in men, with an inverse exposure-risk relationship odds ratios of 0.6, 0.5 and 0.2, respectively, for cumulative consumptions of < 10, 10-23 and > or = 24 pack-years), contrasting with an odds ratios clearly > 1 in women.

Parental occupation, occupational exposure to solvents and polycyclic aromatic hydrocarbons and risk of childhood brain tumors (Italy, France, Spain)

The role of parental occupational exposure in childhood brain tumors was investigated in a population-based case-control study grouping 251 cases and 601 controls from three European centers: Milan (Italy), Paris (France), and Valencia (Spain). Parental occupational exposure to solvents and polycyclic aromatic hydrocarbons (PAH) during the five-year period before birth was estimated using a job-exposure matrix developed earlier in the same countries. Odds ratios (OR) of brain tumors for each occupation and occupational exposure were estimated by logistic regression, adjusting for child's age, gender, exposure to tobacco smoke and ionizing radiation, mother's age and years of schooling, and center. The risk of childhood brain tumors rose when fathers worked in agriculture (OR = 2.2, 95 percent confidence interval [CI] = 1.0-4.7) and motor-vehicle-related occupations. In the latter group, the risk increased for primitive neuroectodermal tumors in particular (OR = 2.7, CI = 1.1-6.6). Astroglial tumors were more frequent among children of mothers in health services (OR = 2.2, CI = 1.0-4.9). Paternal exposure to PAHs was associated with an increased, but not dose-related, risk of primitive neuroectodermal tumors (OR = 2.0, CI = 1.0-4.0), and maternal exposure to solvents at a high level was associated with an increased risk of both astroglial (OR = 2.3, CI = 0.9-5.8) and primitive neuroectodermal tumors (OR = 3.2, CI = 1.0-10.3).

Hairy cell leukaemia and occupational exposure to benzene.

OBJECTIVES: The role of occupational exposures in hairy cell leukaemia (HCL) was investigated through a multicentre, hospital based, case-control study. This paper analyses the role of exposure to benzene in HCL. METHODS: A population of 226 male cases of HCL and 425 matched controls were included in the study. Benzene exposure was evaluated by expert review of the detailed data on occupational exposures generated by case-control interviews. RESULTS: No association was found between HCL and employment in a job exposed to benzene (odds ratio (OR) 0.9 (95% confidence interval (95% CI) 0.6-1.3)). The sample included 125 subjects, 34 cases (15%), and 91 controls (21%) who had been exposed to benzene, as individually assessed by the experts, for at least one hour a month during one of their jobs. Benzene exposure was not associated with a risk of HCL (OR 0.8 (0.5-1.2)). No trend towards an increase in OR was detected for increasing exposures, the percentage of work time involving exposure to > 1 ppm, or the duration of exposure. No findings suggested a particular risk period, when the OR associated with the time since first or last exposure, or since the end of exposure, were examined. CONCLUSIONS: In conclusion, with the low exposures prevalent in the sample, the study did not show any association between benzene exposure and HCL.

Occupational exposure to solvents and hairy cell leukaemia.

OBJECTIVES: The role of occupational exposures in hairy cell leukaemia was investigated through a multicentre, hospital based, case-control study. This paper analyses the role of exposure to solvents other than benzene in hairy cell leukaemia. METHODS: The study included 226 male cases and 425 matched controls, exposure to solvents was evaluated by expert case by case review of the detailed data on occupational exposures generated by specific interviews. Also, exposure to solvents was evaluated with an independently constructed job exposure matrix (JEM). RESULTS: No association was found between hairy cell leukaemia and previous employment in a job exposed to solvents (odds ratio (OR) 0.9 95% confidence interval (95% CI) 0.6 to 1.3). ORs for the main occupational tasks exposed to solvents were around 1 and did not increase with the frequency or the duration of the tasks. No specific type of paint or glue was found to be significantly associated with hairy cell leukaemia. No association was found with exposure to solvents, taken as a whole, with either expert assessments or the JEM. No association was found with aromatic, chlorinated, or oxygenated subgroups of solvents. The ORs did not increase with the average intensity of exposure assessed by the experts, with the frequency of use, or with the duration of exposure. Finally, no association was found with non-occupational exposure to solvents. CONCLUSIONS: The study did not show any association between exposure to solvents and hairy cell leukaemia.

Parental occupations and childhood brain tumors: results of an international case-control study.

OBJECTIVE: To evaluate the role of parental occupations in the etiology of childhood brain tumors (CBT). METHODS: Population-based case-control studies were conducted concurrently in seven countries under the coordination of the International Agency for Research on Cancer, gathering 1,218 cases and 2,223 controls. We report here the findings related to parental occupations during the 5-year period before the child's birth. Risk estimates related to a number of paternal and maternal occupations were obtained by unconditional logistic regression adjusted for age, sex, year of birth, and center, for all types of CBT combined and for the subgroups of astroglial, primitive neuroectodermal tumors (PNET), and other glial tumors. RESULTS: An increased risk in relation with agricultural work was seen for all CBT combined and for other glial tumors. Increased risks for all tumors and PNET were seen for paternal occupation as an electrician; the same pattern held for maternal occupation when children under 5 were selected. Paternal occupation as a driver or mechanic, and maternal work in an environment related to motor-vehicles were associated with an increased risk for all CBT and astroglial tumors. More case mothers compared to control mothers were employed in the textile industry. CONCLUSION: Our study reinforces previous findings relative to the role of parental work in agriculture, electricity, or motor-vehicle related occupations and maternal work in the textile industry. It does not confirm previous associations with work environments including aerospace, the chemical industry, or the food industry, or with maternal occupation as a hairdresser, a nurse, or a sewing machinist, and paternal occupation as a welder.

Congenital malformation and maternal occupational exposure to glycol ethers. Occupational Exposure and Congenital Malformations Working Group.

Glycol ethers are found in a wide range of domestic and industrial products, many of which are used in women's work environments. Motivated by concern about their potential reproductive toxicity, we have evaluated the risk of congenital malformations related to glycol ether exposure during pregnancy as part of a multicenter case-control study, conducted in six regions in Europe. The study comprised 984 cases of major congenital malformations and 1,134 controls matched for place and date of birth. Interviews of the mothers provided information about occupation during pregnancy, sociodemographic variables, and other potential risk factors (medical history, tobacco, alcohol, drugs). A chemist specializing in glycol ethers evaluated exposure during pregnancy, using the job description given by the mother, without knowledge of case or control status. We classified malformations into 22 subgroups. The overall odds ratio (OR) of congenital malformation associated with glycol ether exposure was 1.44 [95% confidence interval (CI) = 1.10-1.90], after adjustment for several potential confounders. The association with exposure to glycol ethers appeared particularly strong in three subgroups: neural tube defects (OR = 1.94; 95% CI = 1.16-3.24), multiple anomalies (OR = 2.00; 95% CI = 1.24-3.23), and cleft lip (OR = 2.03; 95% CI = 1.11-3.73). In this last subgroup, risk, especially of an isolated defect, tended to increase with level of exposure.