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     

Occupational exposures and non-Hodgkin's lymphoma in Southern Sweden

In a case-control study based on 859 consecutive non-Hodgkin's lymphoma (NHL) cases identified through a tumor registry between 1990 and 1998, the authors collected demographic, occupational, exposure, and education information. Exposures were identified through self-report, reported occupational history, and the use of a job-exposure matrix. Conditional logistic regression analyses of the 859 cases and 1,310 controls showed increased risks in workers exposed to gasoline (odds ratio [OR] 1.46; 95% confidence interval [CI] 1.04, 2.05), aliphatic or alicyclic hydrocarbons (OR 1.75; CI 1.03, 2.99), aromatic hydrocarbons (OR 1.45; (CI 1.13, 1.86), and solvents for mole than five years (OR 1.59: CI 1.11, 2.28), as well as automobile mechanics (OR 1.82; CI 1.18, 2.81) and painters (OR 1.77; CI 1.13, 2.76). Exposures to pesticides and farming were not associated with increased risk. Prior radiotherapy was associated with increased risk (OR 2.84; (CI 1.85, 4.37). Concordance between analyses based on self-reported exposures, occupations, and the job-exposure matrix supported the links between organic solvents and prior radiotherapy and NHL but did not support associations between farming or pesticides and NHL.     

The relation of occupational organic solvent exposure to symptom reporting in a sample of white and Chinese midlife women

OBJECTIVE: This study examined the relation of occupational solvent exposure to menopausal and other symptoms in midlife women. METHODS: We conducted a cross-sectional study of 480 Chinese and 494 white women, aged 40-55 years, in Northern California. Levels of exposure to organic solvents (none, low, medium, or high) were assigned to each current job using a job-exposure matrix. RESULTS: A lower proportion of women with low occupational organic solvent exposure reported hot flashes or night sweats than working women with no solvent exposure (adjusted prevalence odds ratio [APOR] = 0.48, 95% confidence interval [CI] = 0.19-1.21). A greater proportion of women with high solvent exposure reported forgetfulness than women with no exposure (APOR = 2.51, 95% CI = 1.12-5.63). CONCLUSIONS: Some symptom reporting in midlife women was related to their occupational organic solvent exposure.     

Occupational risk factors for selected cancers among African American and White men in the United States

OBJECTIVES: This study examined occupational risks for non-Hodgkin's lymphoma, Hodgkin's disease, and soft-tissue sarcoma among African American and White men. METHODS: Race-specific multivariate logistic regression analyses were conducted using data from a large US population-based case-control study. RESULTS: Significant occupational risks were limited to African Americans; chromium was associated with non-Hodgkin's lymphoma (odds ratio [OR] = 3.9, 95% confidence interval [CI] = 1.2, 12.9) and wood dust was associated with Hodgkin's disease (OR = 4.6, 95% CI = 1.6, 13.3) and soft-tissue sarcoma (OR = 3.7, 95% CI = 1.6, 8.6). CONCLUSIONS: Race-specific occupational risk factors for cancer were evident only among African American men. This may reflect racial disparities in levels of exposure to occupational carcinogens.     

Occupational exposure to pesticides and risk of non-Hodgkin's lymphoma

Pesticide exposure may be a risk factor for non-Hodgkin's lymphoma, but it is not certain which types of pesticides are involved. A population-based case-control study was undertaken in 2000-2001 using detailed methods of assessing occupational pesticide exposure. Cases with incident non-Hodgkin's lymphoma in two Australian states (n = 694) and controls (n = 694) were chosen from Australian electoral rolls. Logistic regression was used to estimate the risks of non-Hodgkin's lymphoma associated with exposure to subgroups of pesticides after adjustment for age, sex, ethnic origin, and residence. Approximately 10% of cases and controls had incurred pesticide exposure. Substantial exposure to any pesticide was associated with a trebling of the risk of non-Hodgkin's lymphoma (odds ratio = 3.09, 95% confidence interval: 1.42, 6.70). Subjects with substantial exposure to organochlorines, organophosphates, and "other pesticides" (all other pesticides excluding herbicides) and herbicides other than phenoxy herbicides had similarly increased risks, although the increase was statistically significant only for "other pesticides." None of the exposure metrics (probability, level, frequency, duration, or years of exposure) were associated with non-Hodgkin's lymphoma. Analyses of the major World Health Organization subtypes of non-Hodgkin's lymphoma suggested a stronger effect for follicular lymphoma. These increases in risk of non-Hodgkin's lymphoma with substantial occupational pesticide exposure are consistent with previous work.     

Organic brain damage and occupational solvent exposure.

Three hundred and nine men with organic dementia, cerebral atrophy, or psycho-organic syndrome admitted for five nights or more to one of 18 Quebec hospitals were individually matched with patients admitted (1) with some other psychiatric diagnosis and (2) to a general hospital. Lifetime occupational histories were obtained by telephone. Occupational exposure to solvents was assessed blind to type of case by (1) individual ratings and (2) a job exposure matrix; men who worked in moderate or high solvent concentrations for at least 10 years were considered exposed. With the psychiatric referent series, an odds ratio of 1.4 (90% CI 1.0-2.0) was calculated by individual exposure ratings and 1.4 (90% CI 0.9-2.2) by job matrix. Increased risk was mainly in those with organic dementia or cerebral atrophy and an alcohol related diagnosis. The same pattern of risk was found against the general hospital referents. Adjustment for possible confounders did not alter the risk estimates appreciably. Also, lifetime job histories, compared in selected case-referent pairs, gave similar evidence of increased risk (odds ratio 2.3; 90% CI 1.0-5.5). It is concluded that the combined effect of occupational solvent exposure and alcohol intake is probably an important cause of organic brain damage.     

Organic brain damage and occupational solvent exposure.

Three hundred and nine men with organic dementia, cerebral atrophy, or psycho-organic syndrome admitted for five nights or more to one of 18 Quebec hospitals were individually matched with patients admitted (1) with some other psychiatric diagnosis and (2) to a general hospital. Lifetime occupational histories were obtained by telephone. Occupational exposure to solvents was assessed blind to type of case by (1) individual ratings and (2) a job exposure matrix; men who worked in moderate or high solvent concentrations for at least 10 years were considered exposed. With the psychiatric referent series, an odds ratio of 1.4 (90% CI 1.0-2.0) was calculated by individual exposure ratings and 1.4 (90% CI 0.9-2.2) by job matrix. Increased risk was mainly in those with organic dementia or cerebral atrophy and an alcohol related diagnosis. The same pattern of risk was found against the general hospital referents. Adjustment for possible confounders did not alter the risk estimates appreciably. Also, lifetime job histories, compared in selected case-referent pairs, gave similar evidence of increased risk (odds ratio 2.3; 90% CI 1.0-5.5). It is concluded that the combined effect of occupational solvent exposure and alcohol intake is probably an important cause of organic brain damage.     

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.     

Cancer risk among workers at Danish companies using trichloroethylene: a cohort study

Trichloroethylene is an animal carcinogen with limited evidence of carcinogenicity in humans. Cancer incidence between 1968 and 1997 was evaluated in a cohort of 40,049 blue-collar workers in 347 Danish companies with documented trichloroethylene use. Standardized incidence ratios for total cancer were 1.1 (95% confidence interval (CI): 1.04, 1.12) in men and 1.2 (95% CI: 1.14, 1.33) in women. For non-Hodgkin's lymphoma and renal cell carcinoma, the overall standardized incidence ratios were 1.2 (95% CI: 1.0, 1.5) and 1.2 (95% CI: 0.9, 1.5), respectively; standardized incidence ratios increased with duration of employment, and elevated standardized incidence ratios were limited to workers first employed before 1980 for non-Hodgkin's lymphoma and before 1970 for renal cell carcinoma. The standardized incidence ratio for esophageal adenocarcinoma was 1.8 (95% CI: 1.2, 2.7); the standardized incidence ratio was higher in companies with the highest probability of trichloroethylene exposure. In a subcohort of 14,360 presumably highly exposed workers, the standardized incidence ratios for non-Hodgkin's lymphoma, renal cell carcinoma, and esophageal adenocarcinoma were 1.5 (95% CI: 1.2, 2.0), 1.4 (95% CI: 1.0, 1.8), and 1.7 (95% CI: 0.9, 2.9), respectively. The present results and those of previous studies suggest that occupational exposure to trichloroethylene at past higher levels may be associated with elevated risk for non-Hodgkin's lymphoma. Associations between trichloroethylene exposure and other cancers are less consistent.     

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.     

Non-Hodgkin's lymphomas and organic solvents

Organic solvents have been suggested as a possible risk factor for non-Hodgkin's lymphomas (NHL). We studied 109 NHL incident cases and 276 controls with other cancers (1990/1996) in the city of Salvador, Brazil. Occupational exposure to organic solvents was evaluated through standardized questionnaires and defined by industrial hygienists, taking into account individuals' lifetime history. An association between occupational exposure to organic solvents and NHL was observed, OR = 1.67 (95% CI, 0.97 to 2.87), especially among individuals less than 64 years, OR = 1.91 (95% CI, 0.99 to 3.67), and among those who used domestic insecticides, OR = 2.24 (95% CI, 1.01 to 3.97). Odds ratios were similar for nodal and diffuse NHL. These results suggest that organic solvents may contribute to the causation of NHL, especially among young individuals, and that synergism may play a role in the process of lymphomagenesis.     

Exposure to organic solvents and adverse pregnancy outcome

In a large case-control study (n = 1,926) of spontaneous abortion (SAB), exposure to solvents was ascertained by a telephone interview that asked about occupational use of 18 specific solvents or products, as well as an open-ended "other" solvent category. The adjusted odds ratio for use of any solvent was 1.1 (0.8, 1.5). Solvents for which at least a doubled crude risk of SAB was found included perchlorethylene (OR = 4.7, 95% CI = 1.1, 21.1), trichloroethylene (OR = 3.1, CI = 0.9, 10.4), and paint thinners (OR = 2.3, CI = 1.0, 5.1). Comparing exposure greater than 10 hours per week versus less did not show consistent dose-response effects. By solvent class, an association was seen with aliphatic solvents (adjusted OR = 1.8, 95% CI = 1.1, 3.0), but there was no dose-response effect by hours of use. Household use of solvent-containing products was generally not strongly associated with SAB, nor did it appear to confound the association seen with occupational use. From this and other studies, occupational exposure to at least some solvents appears associated with SAB. The associations of solvent exposure and fetal growth among liveborn offspring of controls was also examined.     

Cancer incidence and mortality in the Swedish polyurethane foam manufacturing industry.

Toluene diisocyanate (TDI) and methylene diphenyldiisocyanate (MDI) are used in large quantities in the polyurethane foam manufacturing industry. Both substances are mutagenic and at least TDI is carcinogenic to animals, but the occupational hazard with respect to cancer is not known. Cancer incidence and mortality patterns were therefore investigated in a cohort of 4154 workers from nine Swedish plants manufacturing polyurethane foam, employed for at least one year. Each workplace and job task in the nine plants was categorically assessed for each calendar year by an experienced occupational hygienist, for "no exposure", "low or intermittent exposure", or "apparent exposure" to TDI and MDI. The observed deficit for all cause mortality (standardised mortality ratio (SMR) 0.78, (95% confidence interval (95% CI) 0.66-0.93) became smaller (SMR 0.92) excluding the first 10 years since the start of exposure and was ascribed to a healthy worker effect. No increased risk for death from bronchial obstructive diseases was found. An almost statistically significant deficit occurred for all malignant neoplasms (standardised incidence ratio (SIR) 0.81, 95% CI 0.63-1.02); slight (not significant) increased risks were found for rectal cancer (SIR 1.66) and non-Hodgkin's lymphoma (SIR 1.53). The SIR for non-Hodgkin's lymphoma increased to 2.80 (95% CI 0.76-7.16) when the first 10 years since first exposure were excluded from the observation period. The corresponding figure for rectal cancer was 1.92 (95% CI 0.52-4.92). Further restricting the analysis to those who had experienced an apparent exposure to TDI or MDI increased the SIR for both rectal cancer (3.19, 95% CI 0.66-9.33), and non-Hodgkin's lymphoma (3.03, 95% CI 0.37-10.9). These estimates were based, however, on few incident cases. As the cohort is still young and little time has elapsed since the start of exposure, future follow ups will enable a more conclusive evaluation.     

Occupational exposure to solvents and the risk of lymphomas

BACKGROUND: A number of studies have shown possible associations between occupational exposures, particularly solvents, and lymphomas. The present investigation aimed to evaluate the association between exposure to solvents and lymphomas (Hodgkin and non-Hodgkin) in a large population-based, multicenter, case-control study in Italy. METHODS: All newly diagnosed cases of malignant lymphoma in men and women age 20 to 74 years in 1991-1993 were identified in 8 areas in Italy. The control group was formed by a random sample of the general population in the areas under study stratified by sex and 5-year age groups. We interviewed 1428 non-Hodgkin lymphoma cases, 304 Hodgkin disease cases, and 1530 controls. Experts examined the questionnaire data and assessed a level of probability and intensity of exposure to a range of chemicals. RESULTS: Those in the medium/high level of exposure had an increased risk of non-Hodgkin lymphoma with exposure to toluene (odds ratio = 1.8; 95% confidence interval = 1.1-2.8), xylene 1.7 (1.0-2.6), and benzene 1.6 (1.0-2.4). Subjects exposed to all 3 aromatic hydrocarbons (benzene, toluene, and xylene; medium/high intensity compared with none) had an odds ratio of 2.1 (1.1-4.3). We observed an increased risk for Hodgkin disease for those exposed to technical solvents (2.7; 1.2-6.5) and aliphatic solvents (2.7; 1.2-5.7). CONCLUSION: This study suggests that aromatic and chlorinated hydrocarbons are a risk factor for non-Hodgkin lymphomas, and provides preliminary evidence for an association between solvents and Hodgkin disease.     

Menstrual and reproductive factors and risk of non-Hodgkin's lymphoma among Connecticut women

Several recent studies have suggested a potential role of menstrual and reproductive factors in the risk of non-Hodgkin's lymphoma. To further examine the relation, the authors analyzed data from a population-based case-control study of non-Hodgkin's lymphoma in Connecticut women between 1996 and 2000. A total of 601 histologically confirmed cases and 717 randomly selected population-based controls were included in this study. An in-person interview was conducted using a standardized and structured questionnaire to collect information on menstrual and reproductive factors and potential confounding factors. Compared with nulliparous women, women who had four or more pregnancies during their lifetime were found to have a significantly reduced risk of non-Hodgkin's lymphoma (odds ratio (OR) = 0.6, 95% confidence interval (CI): 0.4, 0.9). Risk appeared to decrease with increasing number of pregnancies (p(trend) = 0.03). The authors also observed an increased risk of non-Hodgkin's lymphoma overall (OR = 1.5, 95% CI: 1.0, 2.2) and of diffuse non-Hodgkin's lymphoma (OR = 1.7, 95% CI: 1.1, 2.7) for women who started their first menstrual period at age 15 or more years compared with those who started their first menstrual period before age 12 years. These findings support a reduced risk of non-Hodgkin's lymphoma associated with multiple pregnancies and an increased risk of non-Hodgkin's lymphoma associated with later age at menarche.     

Association of obesity and cancer risk in Canada

The authors conducted a population-based, case-control study of 21,022 incident cases of 19 types of cancer and 5,039 controls aged 20-76 years during 1994-1997 to examine the association between obesity and the risks of various cancers. Compared with people with a body mass index of less than 25 kg/m(2), obese (body mass index of > or = 30 kg/m(2)) men and women had an increased risk of overall cancer (multivariable adjusted odds ratio = 1.34, 95% confidence interval (CI): 1.22, 1.48), non-Hodgkin's lymphoma (odds ratio = 1.46, 95% CI: 1.24, 1.72), leukemia (odds ratio = 1.61, 95% CI: 1.32, 1.96), multiple myeloma (odds ratio = 2.06, 95% CI: 1.46, 2.89), and cancers of the kidney (odds ratio = 2.74, 95% CI: 2.30, 3.25), colon (odds ratio = 1.93, 95% CI: 1.61, 2.31), rectum (odds ratio = 1.65, 95% CI: 1.36, 2.00), pancreas (odds ratio = 1.51, 95% CI: 1.19, 1.92), breast (in postmenopausal women) (odds ratio = 1.66, 95% CI: 1.33, 2.06), ovary (odds ratio = 1.95, 95% CI: 1.44, 2.64), and prostate (odds ratio = 1.27, 95% CI: 1.09, 1.47). Overall, excess body mass accounted for 7.7% of all cancers in Canada-9.7% in men and 5.9% in women. This study provides further evidence that obesity increases the risk of overall cancer, non-Hodgkin's lymphoma, leukemia, multiple myeloma, and cancers of the kidney, colon, rectum, breast (in postmenopausal women), pancreas, ovary, and prostate.     

Occupational exposure to organic dust and risk of lymphoma subtypes in the EPILYMPH case–control study

Objectives:This study aimed to estimate the risk of lymphoma and its major subtypes in relation to occupational exposure to specific organic dusts.Methods:We explored the association in 1853 cases and 1997 controls who participated in the EpiLymph case–control study, conducted in six European countries in 1998–2004. Based on expert assessment of lifetime occupational exposures, we calculated the risk of the major lymphoma subtypes associated with exposure to six specific organic dusts, namely, flour, hardwood, softwood, natural textile, synthetic textile, and leather, and two generic (any types) groups: wood and textile dusts. Risk was predicted with unconditional regression modeling, adjusted by age, gender, study center, and education.Results:We observed a 2.1-fold increase in risk of follicular lymphoma associated with ever exposure to leather dust [95% confidence interval (CI) 1.01–4.20]. After excluding subjects who ever worked in a farm or had ever been exposed to solvents, risk of B-cell lymphoma was elevated in relation to ever exposure to leather dust [odd ratio (OR) 2.2, 95% CI 1.00–4.78], but it was not supported by increasing trends with the exposure metrics. Risk of Hodgkin lymphoma was elevated (OR 2.0, 95% CI 0.95–4.30) for exposure to textile dust, with consistent upward trends by cumulative exposure and three independent exposure metrics combined (P=0.023, and P=0.0068, respectively).Conclusions:Future, larger studies might provide further insights into the nature of the association we observed between exposure to textile dust and risk of Hodgkin lymphoma.     

A case-control study of leukemia at a naval nuclear shipyard

A matched case-control study was conducted of 53 leukemia deaths and of 212 controls within a previously studied cohort of 24,545 on-shore workers employed between January 1, 1952 and August 15, 1977 at the Portsmouth (New Hampshire) Naval Shipyard. The study sought to ascertain a priori whether there was an association between leukemia deaths and occupational exposure to either ionizing radiation or organic solvents. To obtain information on individual exposures, radiation dose histories and detailed work histories by job and shop were evaluated for each subject. No statistically significant associations were found either between ionizing radiation or presumed solvent exposure and myelogenous or lymphatic leukemia. However, when specific job categories and shops were examined without benefit of a priori hypotheses, two occupations, electrician and welder, were found to be associated with leukemia. For electricians, the Mantel-Haenszel odds ratio (ORMH) was significantly elevated for all leukemias (ORMH = 3.00, 95% confidence interval (CI) = 1.29-6.98), particularly for lymphatic leukemia (ORMH = 6.00, 95% CI = 1.47-24.45). For welders, the odds ratio was not significantly elevated for all leukemias (ORMH = 2.25, 95% CI = 0.92-5.53), but was significantly elevated for myeloid leukemia (ORMH = 3.83, 95% CI = 1.28-11.46). These findings persisted when potential confounders were adjusted by means of a conditional logistic regression model.     

Hair-coloring product use and risk of non-Hodgkin's lymphoma: a population-based case-control study in Connecticut

A population-based case-control study was conducted in Connecticut in 1996-2002 to test the hypothesis that lifetime hair-coloring product use increases non-Hodgkin's lymphoma risk. A total of 601 histologically confirmed incident female cases and 717 population-based controls were included in the study. An increased risk of non-Hodgkin's lymphoma was observed among women who reported use of hair-coloring products before 1980 (odds ratio = 1.3, 95% confidence interval (CI): 1.0, 1.8). The odds ratios were 2.1 (95% CI: 1.0, 4.0) for those using darker permanent hair-coloring products for more than 25 years and 1.7 (95% CI: 1.0, 2.8) for those who had more than 200 applications. Follicular type, B-cell, and low-grade lymphoma generally showed an increased risk. On the other hand, the authors found no increased risk of non-Hodgkin's lymphoma overall and by subtype of exposure and disease among women who started using hair-coloring products in 1980 or later. It is currently unknown why an increased risk of non-Hodgkin's lymphoma was found only among women who started using hair-coloring products before 1980. Further studies are warranted to show whether the observed association reflects the change in hair dye formula contents during the past two decades or indicates that recent users are still in their induction and latent periods.