Exposure to organic solvents and breast cancer in women: a hypothesis.

Incidence rates for breast cancer have increased steadily over the last 25 years, particularly among postmenopausal women. Secular changes in accepted and suspected risk factors can explain only a part of this increase. Given the increasing number of women in the workforce, it is possible that increases in breast cancer incidence may be caused by occupational exposure to hazardous agents. In particular, we hypothesize that organic solvents act directly as genotoxic agents or indirectly through their metabolites. Most organic solvents are highly lipophilic and are readily absorbed and distributed throughout the body via the bloodstream. Organic solvents are biotransformed mostly in the liver and the kidneys through a series of oxidative and reductive reactions, some of them resulting in bioactivation. There are indications of P-450 enzymatic oxidative activity in the breast parenchyma, but there appears to be limited detoxification of highly reactive metabolites. The physiology of the breast may also accentuate the accumulation of chemicals: breast parenchyma is embedded in a fat depot capable of storing lipophilic xenobiotics; it is conceivable that organic solvents and their metabolites, once stored in fat tissues, migrate to the breast parenchyma and are then transferred to the mammary lobules through continuous apocrine secretions. These secretions may reside in the ductular system long enough for the solvents and their bioactivated metabolites to locally exert detrimental effects. The evidence supporting this hypothesis is that many organic solvents have been detected in breast milk, the majority of carcinomas occur in the ductular system, and some organic solvents have been shown to produce mammary gland cancer in experiments on rodents. Further toxicological and epidemiologic studies are required to test this hypothesis, to elucidate the mechanisms, and to identify specific carcinogenic organic solvents.

Physician based surveillance system for occupational respiratory diseases: the experience of PROPULSE, Québec, Canada.

OBJECTIVE: To evaluate the feasibility of implementing a physician based surveillance system of occupational respiratory diseases (PROPULSE) in Québec with regard to physician participation rate, characteristics of reported cases, and comparison with official statistics from the Workers' Compensation Board (WCB). METHODS: All chest physicians and allergists in Québec were asked to report suspected new cases of occupational respiratory diseases, on a monthly basis, between October 1992 and September 1993. For each case, personal information was collected and the physician's opinion on whether the condition was related to work was categorised as highly likely, likely, and unlikely. RESULTS: Of the 161 physicians initially approached, 68% participated. Physicians rated 48% of suspected cases as highly likely, 29% as likely, and 20% as unlikely. The most often reported diagnosis was asthma (63%), followed by diseases related to asbestos (16%). Silicosis was less frequent (5%) but it was reported for six workers under 40 of whom five were involved in sandblasting activities. The high proportion of cases of asthma probably reflects the increasing importance of this disease but may also reflect the different patterns of reporting among physicians with different expertise. The distribution of cases by diagnostic category is quite different between the PROPULSE system and that of the WCB (annual mean number of compensated cases during a four year period). Asthma and allergic alveolitis are more frequent in PROPULSE, reactive airways dysfunction syndrome are about the same in both systems, and other diseases are more frequent among compensated cases. The most frequent sensitising agents reported for asthma were the same in both systems (isocyanates, flour, and wood dust). 15% of the PROPULSE cases were not covered by the WCB, and therefore would not be found in the board's official statistics. CONCLUSIONS: A physician based reporting procedure can be implemented as part of a surveillance system to supplement data from other sources and thus provide a better understanding of the occurrence of occupational respiratory diseases.

[Study of a cancer aggregate in a metallurgy plant: practical implications for public health]. / Etude d'un agrégat de cancer dans une enterprise de métallurgie: implications pratiques pour la santé publique.

We present the strategy used to determine whether there was an excess of laryngeal cancer at a primary metal factory in Montreal. The study period extended from 1968 to 1987. Standardized mortality ratios (SMR) and standardized incidence ratios (SIR) were computed for different cancer sites. The number of person-years at risk was estimated (N = 10,860 person-years). This method permitted a summary evaluation of the situation. Statistically significant excesses were not observed for laryngeal cancer or any other site of cancer: SMRs and SIRs were elevated for certain cancers, particularly cancers of the larynx and cancers of the central nervous system (CNS). No association was observed with potential carcinogens in the workplace. However, all three CNS cancer cases were crane operators. Following this investigation, we recommended an industrial hygiene evaluation of the workplace.

Psychiatric disorders and occupational exposure to solvents.

Three hundred and eighty one men admitted to hospital for the first time with any psychiatric diagnosis were individually matched for age and year to patients admitted to general hospitals. An occupational history was obtained from 90% of this study group by telephone interview or mail. Exposure to solvents was assessed by three methods, individual rating of each job recorded, application of an exposure matrix based on job title, and assessment of lifetime job histories of selected case-referent pairs. A sample of individual ratings used in the analysis was compared with ratings made by five experts. The panel values tended to be lower but all six sets of ratings correlated well. There was no increased risk of psychiatric illness among subjects exposed to moderate or greater solvent concentrations for at least 10 years (odds ratio (OR) 1.0, 90% confidence interval (90% CI) 0.7-1.4, individual rating; OR 1.1, 90% CI 0.6-2.0, job title matrix; OR 0.9, 90% CI 0.5-1.7, lifetime assessments). At higher exposures the risk was increased--although not to a statistically significant degree--especially for cases with non-psychotic diagnoses (ICD-9 codes 300-316). This negative result, by all three methods of assessment of exposure, contrasted with that from a parallel investigation of cases of organic psychoses and cerebral degeneration.

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.