Canadian Environmental Protection Act, 1999

Carcinogenic and toxicologic effects of inhaled ethylene oxide and propylene oxide in F344 rats

The formation of N-(2-hydroxyethyl)valine (HEVal) in hemoglobin was investigated in male F344 rats (10/group) and B6C3F1 mice (20/group) exposed to 0, 3, 10, 33, 100, or 300 (rats only) ppm ethylene oxide (ETO) by inhalation for 6 h/day for 4 weeks (5 days/week) or exposed to 100 (mice) or 300 ppm (rats) ETO for 1 or 3 days, or 1, 2, or 4 weeks (5 days/week) The persistence of HEVal was studied in animals killed up to 10 days after cessation of the 4-week time-course studies HEVal was determined by a modified Edman degradation and quantitation of the resulting pentafluorophenylthiohydantoin derivative, using gas chromatography-mass spectrometry The resulting experimental data were compared to simulations derived with a model for the formation and removal of hemoglobin adducts (TR Fennell, SCJ Sumner, and VE Walker, Cancer Epidemiol, Biomarkers & Prev, 1: 213-219, 1992) Repeated exposures of rats and mice for 4 weeks to 300 and 100 ppm ETO, respectively, led to an accumulation of HEVal that was 14 (rats) and 15 (mice) times greater than that found after 1 day of exposure [28 +/- 2 (SE) and 94 +/- 04 (SE) pmol HEVal/mg globin in rats and mice, respectively] After cessation of exposures, HEVal was lost faster than predicted by the normal erythrocyte life span alone An initial phase of rapid decline in HEVal concentrations was consistent with the removal of older, more heavily alkylated populations of RBCs, accompanied by a burst of erythropoiesis The dose-response curves for HEVal were linear between 3 and 33 ppm ETO, with 35 +/- 02 and 34 +/- 03 pmol adduct/mg globin formed in rats and mice, respectively, after 4 weeks of exposure to 3 ppm ETO Above 33 ppm ETO, the slope of the dose-response curves increased Comparison of the dose response for HEVal in rats exposed to ETO for 4 weeks to the dose-response for N tau-(2-hydroxyethyl)histidine in rats exposed to the same concentrations of ETO for 2 years (S Osterman-Golkar et al, Teratog Carcinog Mutagen, 3: 395-405, 1983) suggested that exposures to ETO can reduce the life span of erythrocytes in a concentration- and time-dependent manner Correlation of the experimental data and simulations for the formation and removal of HEVal demonstrated that perturbations in erythropoiesis and RBC life span complicate the estimation of exposures to ETO when estimates are based upon hemoglobin adduct measurements in heavily exposed individuals(ABSTRACT TRUNCATED AT 400 WORDS)

https://cancerres.aacrjournals.org/content/canres/52/16/4328.full.pdf

Molecular dosimetry of ethylene oxide: formation and persistence of 7-(2-hydroxyethyl)guanine in DNA following repeated exposures of rats and mice

A two-year inhalation study of the carcinogenic potential of ethylene oxide in fischer 344 rats

The mortality and incidence of cancer in three groups of workers with occupational exposure to ethylene oxide have been assessed. Eight cases of leukemia have occurred among 733 ethylene oxide-exposed workers compared with an expected 0.8 cases. Six cases of stomach cancer have been reported compared with 0.65 cases expected. These epidemiologic results provide support for an increased risk of malignancy in individuals with extended and intermittent exposure to low concentrations of ethylene oxide.

Epidemiologic support for ethylene oxide as a cancer-causing agent.

Because of reports linking an increased risk of leukemia with exposure to ethylene oxide, a mortality study of workers with potential exposure the ethylene oxide at the Texaco Chemical Company Plant in Port Neches, Tex., was undertaken. A total of 767 males with potential exposure to ethylene oxide were identified. Forty-six deaths occurred in this cohort with 80 expected (standardized mortality ration; SMR = 58). No deaths from leukemia were seen, nor were there any statistically significant excesses from any specific causes of death.

Mortality among ethylene oxide workers.

Information has been obtained on a cohort of 16,243 men employed for at least one year in the manufacture of paint or vanish after January 1, 1946, and for seven subgroups on the basis of exposure. These workers experienced a level of mortality that compares favorably with that of the U.S. white male population. The workers' pattern of mortality differed somewhat from the U.S. pattern, with considerably reduced mortality from psychiatric, metabolic, respiratory, and violent causes. There was an increased mortality due to bowel and rectal cancer. While the numbers are smaller, there are also increased rates for liver and skin cancer. Lung cancer rates, while not in excess of the national average, did not match the low mortality from nonmalignant, noninfectious respiratory disease. The authors have concluded that work in this industry presents no major health hazard.

A general mortality study of production workers in the paint and coatings manufacturing industry. A preliminary report

Extensive follow-up of production workers in the paint and coatings industry failed to indicate any important hazard that was previously unsuspected. The authors are more confident of the results of their original study since studying a subsample of persons lost to follow-up in the original study. Some efforts to investigate certain diseases (skin and liver cancer) more vigorously met with failure, which illustrates the problem of attempting retrospective studies by using death certificates for case ascertainment. Of the successful studies, the leukemia case-control analysis showed a possible relationship to lacquer production, which probably included benzene exposure. For lung cancer, no exposure category was associated with increased risk. The bowel cancer excesses, concentrated in three plants, are probably not job related and in any case do not represent an industry-wide problem. Cerebrovascular accidents showed a mild elevation of risk for vehicle workers. Although strong statements concerning the safety of this industry probably await more studies or further follow-up of this cohort, there is every indication that it is an industry without a major excess of any job-related disease. In drawing this conclusion, however, one must be aware that an individual job or individual plant could harbor health problems that would not be detected by a study of this type.

Robert W. Morgan

Papers

Mortality among ethylene oxide workers.

A general mortality study of production workers in the paint and coatings manufacturing industry. A preliminary report

Mortality of paint and coatings industry workers. A follow-up study.

Questions raised by study on cancer mortality in oil refinery workers.