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Cancer risk assessment for 1,3-butadiene: dose-response modeling from an epidemiological perspective.

The dose-response assessment of the association between 1,3-butadiene (BD) and leukemia mortality among workers in the North American synthetic rubber industry is explored. Analyses are based on the most recent University of Alabama at Birmingham epidemiological study and exposure estimation. The U.S. EPA Science Advisory Board recommendations of using the most recent data and giving consideration to peak exposures to BD have been followed. If cumulative BD ppm-years is to be used as the predictor of the leukemia rate ratio, then the performance of that predictor is statistically significantly improved if the slope in the predictor is estimated with age and the cumulative number of BD peaks (where a BD peak is any exposure, regardless of duration, to a BD concentration above 100 ppm) added as categorical covariates. After age and the cumulative number of BD peaks are incorporated as categorical covariates in the Poisson regression model, the estimated concentration (EC(001)) corresponding to an excess risk of 0.001 as a result of continuous environmental exposure is 11.2 ppm; however, the estimated slope for BD cumulative ppm-years in the linear rate ratio for leukemia used to derive this EC(001) is not statistically significantly different from zero. Sensitivity analyses using alternative models indicate either essentially no risk or estimated EC(001) values of 9 and 77 ppm. Analyses suggesting the absence of a statistically significant low-dose risk versus cumulative BD ppm-years are presented. Sensitivity analyses of other malignant neoplasms of lymphatic and hematopoietic tissue (specifically, lymphoid and myeloid neoplasms) resulted in conclusions about the dose-response modeling methodology that were supportive of the methodology used for leukemia.

Aging↗

Metastasis of a well-differentiated liposarcoma in a dog and a note on nomenclature of fatty tumours.

A slow-growing mass in the left thigh of a 7-year-old spayed female fox terrier dog was originally diagnosed as an infiltrative lipoma by surgical biopsy. Necropsy findings one year later revealed multiple masses made up of well-differentiated adipocytes in the spleen, liver, lungs and a lymph node. The final histopathological diagnosis of these masses and, in retrospect, for the initial leg mass was well-differentiated liposarcoma. This case illustrates some of the confusion in current nomenclature of fatty tumours. Tumours made up of well-differentiated adipose cells which show no tendency toward invasion of surrounding tissue should be designated lipomas. We suggest that fatty tumours characterized by local tissue invasion and/or metastasis should be classified as liposarcomas. Liposarcomas may be further subdivided into well-differentiated and poorly-differentiated types.

Animals↗

Survival of Danish cancer patients 1943-1987. Lymphatic and haematopoietic tissues.

In Denmark, 6.6% of all malignant neoplasms among men and 5.5% among women occur in the lymphatic and haematopoietic tissues. Most are generalized when diagnosed, although lymphomas are sometimes confirmed to one region. Treatment has been predominantly by chemotherapy since the 1960s, and is often combined with radiation for lymphomas and myeloma. The five-year survival rates for non-Hodgkin's lymphoma improved by 20% between 1970 and 1987. An improvement in survival from Hodgkin's disease began earlier, with a relative five-year survival rate of about 30% in 1960 and of 72% in 1983-87. Survival was better for younger patients (< 50 years) with stage I-II disease, the relative five-year survival rates being 83-93% in 1983-87. For cases of leukaemia much of the improvement in survival rates was founded in 1960s on success in the treatment of childhood leukaemia (acute lymphatic leukaemia); the relative five-year survival rates for children under 10 years of age increased from 12% to 75-80%. Smaller improvements were seen in survival from other types of leukaemia, including the chronic forms. Thus, even for chronic lymphocytic leukaemia, which has a favourable prognosis but is regarded as incurable, improvements in survival rates were seen, which may be attributed to chemotherapeutic treatment or earlier diagnosis. It was not surprising that the dramatic improvement in survival rates coincided with the introduction of chemotherapeutic treatment regimes, as reported previously in clinical series. Acute and chronic cytotoxic side-effects are of concern, and, since both cytotoxic drugs and radiation are potent carcinogens, second primary cancers have been reported to be induced by treatment of cancers (Storm & Prener, 1985). The improvements in the survival rates for the haematopoietic malignancies, however, outweigh the de novo cancer risk related to therapy.

Adolescent↗

Are chromosome aberrations in circulating lymphocytes predictive of future cancer onset in humans? Preliminary results of an Italian cohort study.

To investigate the existence of an association between the frequency of chromosome aberrations (CA) in non-target tissues and cancer risk, a historical cohort study was carried out in a group of 1455 subjects screened for CA over the last 20 years in Italy. Statistically significant increases in standardized mortality ratio (SMR) for all cancers were found in subjects with medium and high levels of CA in peripheral blood lymphocytes (SMR = 178.5 and SMR = 182.0, respectively) and in subjects with high levels of CA for respiratory tract cancers (SMR = 250.8) and lymphatic and hematopoietic tissue neoplasms (SMR = 548.8). Significant trends in the SMRs were observed for these latter causes of death.

Chromosome Aberrations↗

Cancer mortality among chemical workers in an Italian plant.

Objective of this study was to assess the mortality experience of a cohort of chemical workers at a plant located in central Italy. Subjects employed for any time between 1954 and 1970 at the chemical plant were included in the cohort and followed up to June 1991. The workers were classified as having ever/never worked in one of the following work processes: organic chemicals, acid mixtures, cleansing agents and insecticides. Mortality experience of the cohort was compared with that of the regional population by computing SMRs (standardized mortality ratios) and 90% CI (confidence intervals). Vital status was ascertained for 96% of the 505 cohort members. All causes of mortality for the entire cohort were lower than expected (Obs: 176; SMR: 0.90; 90% CI: 0.79-1.03). Analysis by work process revealed an increased mortality for lymphatic and hematopoietic tissue neoplasm in the cleansing agents department (Obs: 3; SMR: 5.00; 90% CI: 1.36-12.9); peritoneum and retropertioneum neoplasm in the organic compounds production (Obs: 2; SMR: 13.33; 90% CI: 2.37-42.0), and bladder cancer in the insecticides process (Obs: 3; SMR: 3.53; 90% CI: 0.96-9.12). Although the study had a low statistical power, the increased cancer risks detected are consistent with previous observations and may be of etiologic interest.

Adult↗

A prospective study of morbidity patterns in a petroleum refinery and chemical plant.

This study examined the morbidity experience from 1981 to 1988 of a prospective cohort of 3422 refinery and petrochemical plant employees from the Shell Deer Park manufacturing complex. The morbidity data for this study, which include all illness and absence records in excess of five days, were extracted from the morbidity section of the Shell health surveillance system. Standardised morbidity ratios (SMRs) of disease prevalence in this cohort were calculated using an internal comparison group of all manufacturing employees of the Shell Oil Company. Among production employees, the overall morbidity was statistically significantly higher (SMR = 109) than that of the comparison group. Illness due to hypertension (SMR = 144), haemorrhoids (SMR = 149), diseases of the nervous system (SMR = 120), respiratory system (SMR = 108), and digestive system (SMR = 117) were also raised for this group. The increased risk due to these medical conditions does not appear to be associated with occupational factors. Lymphatic and haematopoietic tissue neoplasms were raised (SMR = 124), but were based on only four cases.

Acute Disease↗

Cancer mortality in a historical cohort study of workers exposed to styrene.

OBJECTIVES: The goal of this study was to determine whether exposure to styrene is associated with an increased risk for neoplasms of the lymphatic and hematopoietic tissues. METHODS: A historical cohort study was conducted in Denmark, Finland, Italy, Norway, Sweden, and the United Kingdom. It involved 40,688 workers ever employed in the reinforced plastics industry, where high exposure to styrene occurs. Exposure to styrene was reconstructed through job histories and environmental and biological monitoring data. Cause-specific national death rates were used as the reference. Poisson regression was applied for internal comparisons. RESULTS: Among the exposed workers, no excess was observed for mortality from all neoplasms. Mortality from neoplasms of the lymphatic and hematopoietic tissues increased with time since first exposure and average level of exposure to styrene, but was not consistently associated with duration of exposure or with cumulative exposure. CONCLUSIONS: These findings leave open the possibility of an excess risk of neoplasms of the lymphatic and hematopoietic tissues among workers exposed to styrene.

Cohort Studies↗