Kenneth M. Bodner

Chronic toxicity and oncogenicity study on acrylamide incorporated in the drinking water of Fischer 344 rats

Male and female Fischer 344 rats were maintained on treated drinking water providing dosages of 0 (controls), 0.01, 0.1, 0.5, or 2.0 mg acrylamide/kg body wt/day for 2 years to assess the chronic toxicity and oncogenic potential of the chemical. The mean body weights of male and female rats receiving 2.0 mg/kg/day and of male rats receiving 0.5 mg/kg/day were minimally decreased when compared with controls. During the last 4 months of the study, there was an increase in mortality among male and female rats receiving 2.0 mg/kg/day. A target organ effect, characterized by degeneration of peripheral nerves, was observed in rats receiving 2.0 mg/kg/day. The incidence of several tumor types was increased in the rats receiving 2.0 mg/kg/day when compared with controls. In females, increased tumor incidences were observed in the mammary gland, central nervous system, thyroid gland-follicular epithelium, oral tissues, uterus, and clitoral gland. In males the incidence of tumors of the thyroid gland-follicular epithelium and scrotal mesothelium was increased. Male rats receiving 2.0 mg/kg/day also had increased incidence of central nervous system tumors when compared to historical controls but not when compared to concurrent controls. The only tumor incidence which was significantly increased at the 0.5 mg/kg/day level was scrotal mesothelioma. There was no statistically significant increase of any tumor type at the 0.1 or 0.01 mg/kg/day dose levels. However, the incidence of scrotal mesothelioma at the 0.1 mg/kg/day level was greater than that observed in the control group or historically reported in this laboratory.

Have sperm counts been reduced 50 percent in 50 years ? A statistical model revisited

OBJECTIVE To reanalyze data that were used in a linear model to predict that mean sperm counts have been reduced globally by approximately 50% in the last 50 years. DESIGN The mean sperm counts and their temporal distribution were reanalyzed via several different statistical models (quadratic, spline fit, and stairstep). CONCLUSION There are several reasons why a published linear regression model is inappropriate to infer a 50% reduction in mean sperm counts in the last 50 years. These include [1] the potential selection biases that may have occurred with the 61 assembled studies such that they are not representative of their underlying populations; [2] the likely variability in collection methods, in particular, the lack of adherence to a minimum prescribed abstinence period, as has been stated for the largest study, which contained 29.7% of all the subjects included in the analysis; [3] the paucity of data in the first 30 years of the 50-year trend analysis; [4] the fact that if the last 20 years of data are examined, which contains 78.7% of all the studies and 88.1% of the total number of subjects, there is no decrease in sperm counts, in fact, sperm counts were observed to have increased; [5] the conflicting data from a large individual laboratory, which was not prone to the collection variability that likely occurred between the 61 studies, that did not suggest a decline in mean sperm count or seminal volume during a comparable time period, even though this laboratory published the data that were largely responsible for the high historical values in the linear model; and, most importantly, [6] the variety of other mathematical models that perform statistically better at describing the recent data than the linear model and thus offer substantially different hypotheses. The data are only robust during the last 20 years of the analysis, in which all the models, except the linear model, suggest constant or slightly increasing sperm counts.

Cancer risk for chemical workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin

Aims: To describe the long term mortality experience of a cohort of 2187 male chemical production workers previously exposed to substantial levels of dioxin. Methods: Vital status for a previously identified cohort was determined for an additional 10 years, to 1995. Dioxin exposures took place before 1983 and were sufficient to result in chloracne in 245 individuals. Mortality rates were compared with national figures and with a large pool of co-workers in unrelated production jobs. Results: All cancers combined (standardised mortality ratio (SMR) = 1.0, 95% CI 0.8 to 1.1) and lung cancer (SMR = 0.8, 95% CI 0.6 to 1.1) were at or below expected levels. Rates for soft tissue sarcoma (SMR = 2.4, 95% CI 0.3 to 8.6) and non-Hodgkin’s lymphoma (SMR = 1.4, 95% CI 0.6 to 2.7) were greater than expected overall, but below expectation in the update period. No trend of increasing risk with increasing exposure was observed for these cancers. Workers who developed chloracne had very low all-cancer rates (SMR = 0.5, 95% CI 0.3 to 1.0), and lung cancer rates (SMR = 0.3, 95% CI 0.0 to 1.1). Conclusions: We found no coherent evidence of increased cancer risk from dioxin exposure in this cohort. Our study highlights the wide range of cancer rates and the lack of consistency across dioxin studies.

Mortality Rates Among Trichlorophenol Workers With Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin

The authors examined 1,615 workers exposed to dioxins in trichlorophenol production in Midland, Michigan, to determine if there were increased mortality rates from exposure. Historical dioxin levels were estimated by a serum survey of workers. Vital status was followed from 1942 to 2003, and cause-specific death rates and trends with exposure were evaluated. All cancers combined (standardized mortality ratio (SMR) = 1.0, 95% confidence interval (CI): 0.8, 1.1), lung cancers (SMR = 0.7, 95% CI: 0.5, 0.9), and nonmalignant respiratory disease (SMR = 0.8, 95% CI: 0.6, 1.0) were at or below expected levels. Observed deaths for leukemia (SMR = 1.9, 95% CI: 1.0, 3.2), non-Hodgkin lymphoma (SMR = 1.3, 95% CI: 0.6, 2.5), diabetes (SMR = 1.1, 95% CI: 0.6, 1.8), and ischemic heart disease (SMR = 1.1, 95% CI: 0.9, 1.2) were slightly greater than expected. No trend was observed with exposure for these causes of death. However, for 4 deaths of soft tissue sarcoma (SMR = 4.1, 95% CI: 1.1, 10.5), the mortality rates increased with exposure. The small number of deaths and the uncertainty in both diagnosis and nosology coding make interpretation of this finding tenuous. With the exception of soft tissue sarcoma, the authors found little evidence of increased disease risk from exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Mortality study update of acrylamide workers

Objective: The authors examined the long-term health effects of occupational exposure to acrylamide among production and polymerisation workers. Methods: An earlier study of 371 acrylamide workers was expanded to include employees hired since 1979. In this updated study, 696 acrylamide workers were followed from 1955 through 2001 to ascertain vital status and cause of death. Exposure to acrylamide was retrospectively assessed based on personal samples from the 1970s onwards and area samples over the whole study period. Results: Fewer of the acrylamide workers died (n = 141) compared to an expected number of 172.1 (SMR 81.9, 95% CI 69.0 to 96.6). No cause-specific SMR for any of the investigated types of cancer was exposure related. The authors did, however, find more pancreatic cancer deaths than expected (SMR 222.2, 95% CI 72.1 to 518.5). With respect to non-malignant disease, more diabetes deaths were observed than expected (SMR 288.7, 95% CI 138.4 to 531.0). To assess the influence of regional factors, the analysis was repeated with an internal reference population. The elevated SMR for diabetes persisted. Conclusion: This study provides little evidence for a cancer risk from occupational exposure to acrylamide at production facilities. However, the increased rates of pancreatic cancer in this study and another larger study of acrylamide production workers indicate that caution is needed to rule out a cancer risk. The authors believe that the excess of diabetes mortality in this study is most likely not related to acrylamide exposure, because a larger study of acrylamide workers reported a deficit in this cause of death. The authors conclude that the increased SMR for diabetes mortality is probably not related to regional influences.

Evaluation of the OECD activated sludge, respiration inhibition test

Abstract The OECD Activated Sludge, Respiration Inhibition Test was evaluated as a method for assessing the potential impact of chemicals on wastewater treatment systems. Reproducibility of the test method was examined with respect to variation in oxygen consumption rates measured for a series of reactions set under identical conditions, and the variability in IC50 values estimated for three reference compounds. Several statistical procedures were also evaluated for analyzing activated sludge inhibition data. The test method was subsequently used to examine the effects of a wide variety of inorganic and organic chemicals on activated sludge respiration rates.

Cancer mortality of workers exposed to styrene in the U.S. Reinforced plastics and composite industry.

Background: Epidemiologic studies have reported increased risk of lymphohematopoietic cancers, lung cancer, and pancreatic cancer after exposure to styrene, although findings across studies are not consistent. Methods: We update a large study of reinforced plastic industry workers with relatively high exposures to styrene, examining cancer risks associated with exposure levels. The study includes 15,826 workers who were exposed between 1948 and 1977 with vital-status follow-up from 1948 to 2008. We examine mortality rates associated with cumulative exposure, duration of exposure, peak exposures, average exposure, and time since first exposure to styrene. Exposure estimates were truncated starting in 1977, the period with the lowest exposures, leaving 27% of the study group with incomplete work histories. Results: The standardized mortality ratios were 0.84 (95% confidence interval = 0.69–1.02) for all lymphatic and hematopoietic cancers combined, 0.72 (0.50–1.00) for non-Hodgkin lymphoma, and 0.84 (0.60–1.14) for leukemia. There was no trend with either cumulative exposure to styrene or number of peaks. Pancreatic cancer deaths were at expected levels (0.96 [0.73–1.22]). There were more lung cancer deaths than expected (1.34 [1.23–1.46]), although with a marked inverse trend with cumulative exposure. Conclusion: We found no coherent evidence that styrene exposure increases risk from cancers of the lymphatic and hematopoietic tissue, pancreas, or lung.

Mortality rates among workers exposed to dioxins in the manufacture of pentachlorophenol.

Objective: We sought to determine if workers exposed to dioxins in pentachlorophenol (PCP) manufacturing were at increased risk of death from specific causes. Methods: We examined death rates among 773 workers exposed to chlorinated dioxins during PCP manufacturing from 1937 to 1980 using serum dioxin evaluations to estimate exposures to five dioxins. Results: Deaths from all causes combined, all cancers combined, lung cancer, diabetes, and ischemic heart disease were near expected levels. There were eight deaths from non-Hodgkin lymphoma (standardized mortality ratios = 2.4, 95% CI = 1.0 to 4.8). We observed no trend of increasing risk for any cause of death with increasing dioxin exposure. However, the highest rates of non-Hodgkin lymphoma were found in the highest exposure group (standardized mortality ratios = 4.5, 95% CI = 1.2 to 11.5). Conclusions: Other than possibly an increased risk of non-Hodgkin lymphoma, we find no other cause of death related to the mixture of the dioxin contaminants found in PCP.

Mortality from pancreatic and lymphopoietic cancer among workers in ethylene and propylene chlorohydrin production

OBJECTIVES: A previous study reported a fivefold increase in mortality from pancreatic cancer and a threefold increase in lymphopoietic and haematopoietic cancer among 278 men who were assigned to a now dismantled Union Carbide chlorohydrin unit in the Kanawha Valley of West Virginia. There were also significant trends with duration of employment. The purpose of this study was to determine whether a comparable increased risk in mortality from pancreatic cancer and lymphopoietic and haematopoietic cancer occurred among male employees assigned to the Dow Chemical Companys ethylene and propylene chlorohydrin production processes. METHODS: The cohort consisted of 1361 male employees who worked at the companys Freeport, Texas, Plaquemine, Louisiana or Midland, Michigan plants. Subjects were considered to have had a minimum of 30 days of workplace experience in 1940-92, in the ethylene chlorohydrin and propylene chlorohydrin process areas. These process areas were located within the ethylene oxide and propylene oxide production plants. A total of 300 deaths was observed to 31 December 1992. RESULTS: The standardised mortality ratio (SMR) for all malignant neoplasms was 94 (95% CI 74 to 118). There was one pancreatic cancer death compared with 4.0 expected (SMR 25, 95% CI 1 to 140). There were 10 lymphopoietic and haematopoietic cancer deaths compared with 7.7 expected (SMR 129, 95% CI 62 to 238). Additional analyses, which examined location, production process, duration of employment, and a 25 year induction latency period, were not significant. CONCLUSIONS: The results provide some assurance that the Dow Chemical cohort, to date, has not experienced increased risks of pancreatic cancer and lymphopoietic and haematopoietic cancer as previously reported in a different cohort of chlorohydrin workers. Possible reasons are discussed for the inconsistent findings between the two cohorts.

Serum concentrations of chlorinated dibenzo-p-dioxins and dibenzofurans among former Michigan trichlorophenol and pentachlorophenol workers

This study examines serum levels of 2,3,7,8-substituted chlorinated dioxins and furans, and PCBs for 375 Michigan workers with potential chlorophenol exposure, 37 Worker Referents, and 71 Community Referents. The chlorophenol workers were last exposed to trichlorophenol and/or pentachlorophenol 26–62 years ago. Employees working only in the trichlorophenol units had mean lipid-adjusted 2378-tetrachlorodibenzo-p-dioxin (TCDD) levels of 15.9 ppt compared with 6.5 ppt in the Worker Referents. Employees working only in the pentachlorophenol units had mean lipid-adjusted levels for 123478-H6CDD of 16.1 ppt, 123678-H6CDD of 150.6 ppt, 123789-H6CDD of 20.2 ppt, 1234678-H7CDD of 192.6 ppt, and OCDD of 2,594.0 ppt compared with the Worker Referent levels for the same congeners of 7.5, 74.7, 8.6, 68.7, and 509.1 ppt, respectively. All furan and PCB levels among workers in the trichlorophenol and/or pentachlorophenol departments were similar to the Worker Referents. The Tradesmen who worked throughout the plant had dioxin congener profiles consistent with both trichlorophenol and pentachlorophenol exposures. PCB levels and levels of 23478-P5CDF, 123478-H6CDF, and 123678-H6CDF were also greater in these Tradesmen than in the Worker Referents. The Worker Referent group had higher levels of dioxins and furans than the Community Referents indicating the potential for exposure outside the chlorophenol departments at the site. Distinct patterns of dioxin congeners were found many years after exposure among workers with different chlorophenol exposures. Furthermore, past trichlorophenol exposures were readily distinguishable from past pentachlorophenol exposures based on serum dioxin evaluations among workers. These data can be used to better assess dioxin exposures in future health studies.