Rubber Hydrochloride Research Articles

The Impact of Saturable Metabolism on Exposure-Response Relations in 2 Studies of Benzene-induced Leukemia

Enzymatic saturation of metabolic pathways is one factor that potentially contributes to the nonlinear exposure-response relations that are frequently reported in occupational epidemiologic studies. The authors propose an approach to explore the contribution of saturable metabolism to previously reported exposure-response relations by integrating predictive models of relevant biomarkers of exposure into the epidemiologic analysis. The approach is demonstrated with 2 studies of leukemia in benzene-exposed workers, one conducted in the Australian petroleum industry (1981-1999) and one conducted in a US rubber hydrochloride production factory in Ohio (1940-1996). The studies differed greatly in their magnitudes and durations of exposure. Substitution of biomarker levels for external estimates of benzene exposure reduced the fold difference of the log relative risk of leukemia per unit of cumulative exposure between the 2 studies by 11%-44%. Nevertheless, a considerable difference in the log relative risk per unit of cumulative exposure remained between the 2 studies, suggesting that exposure misclassification, differences in study design, and potential confounding factors also contributed to the heterogeneity in risk estimates.

Multistage Modeling of Leukemia in Benzene Workers: A Simple Approach to Fitting the 2-Stage Clonal Expansion Model

A simple SAS software program (SAS Institute, Inc., Cary, North Carolina) was developed for fitting an exact formulation of the 2-stage clonal expansion model accommodating piecewise constant exposures and left and right censoring of observations. Data on leukemia mortality and occupational exposure to benzene among rubber hydrochloride production workers in Ohio (1940-1996) were analyzed by using this approach. A model in which benzene exposure increased clonal expansion fit these data well; little evidence of an association between benzene exposure and initiation of leukemia was found. The estimated exposure-response association increased in magnitude with age at exposure and decreased with time since exposure. This analysis shows that the 2-stage clonal expansion model can be readily fit to epidemiologic cohort data by using a simple SAS program. The illustrative analyses of leukemia mortality among rubber hydrochloride workers suggest that the effect of benzene on leukemia risk is due to an exposure-induced increase in the proliferation of initiated cells.

Temporal variation in the association between benzene and leukemia mortality.

BackgroundBenzene is a human carcinogen. Exposure to benzene occurs in occupational and environmental settings.ObjectiveI evaluated variation in benzene-related leukemia with age at exposure and time since exposure.MethodsI evaluated data from a cohort of 1,845 rubber hydrochloride workers. Benzene exposure–leukemia mortality trends were estimated by applying proportional hazards regression methods. Temporal variation in the impact of benzene on leukemia rates was assessed via exposure time windows and fitting of a multistage cancer model.ResultsThe association between leukemia mortality and benzene exposures was of greatest magnitude in the 10 years immediately after exposure [relative rate (RR) at 10 ppm-years = 1.19; 95% confidence interval (CI), 1.10–1.29]; the association was of smaller magnitude in the period 10 to < 20 years after exposure (RR at 10 ppm-years = 1.05; 95% CI, 0.97–1.13); and there was no evidence of association ≥ 20 years after exposure. Leukemia was more strongly associated with benzene exposures accrued at ≥ 45 years of age (RR at 10 ppm-years = 1.11; 95% CI, 1.04–1.17) than with exposures accrued at younger ages (RR at 10 ppm-years = 1.01; 95% CI, 0.92–1.09). Jointly, these temporal effects can be efficiently modeled as a multistage process in which benzene exposure affects the penultimate stage in disease induction.ConclusionsFurther attention should be given to evaluating the susceptibility of older workers to benzene-induced leukemia.

Exposure to benzene and non-Hodgkin lymphoma, an epidemiologic overview and an ongoing case-control study in Shanghai

The interest in the relationship between benzene exposure and non-Hodgkin lymphoma (NHL) appears to have been generated from a 1979 publication, which reported an increased risk of NHL among persons potentially exposed to benzene and/or coal tar fractions. More recently (1997), an increased risk of NHL was reported among 74,828 workers exposed to benzene and other chemicals in a variety of industries in China. On the contrary, no increased risk of NHL was reported in a cohort of 1,165 workers at two rubber hydrochloride plants in Ohio (US), who were exposed to extremely high levels of benzene and were found to have an increased risk of acute myeloid leukemia. In another large cohort of some 7,676 US workers exposed to benzene, no increased risk of NHL was reported. Similarly, no increased risk of NHL was reported in a combined cohort of 308,199 petroleum workers in the US, the UK, Canada, Australia, Italy and Finland, who were exposed to benzene or benzene-containing petroleum products. The lack of an association between benzene exposure and NHL in cohort studies is supported by case-control studies from the US, Canada, Italy and the UK. To further investigate the relationship between benzene exposure and NHL, we are conducting a hospital-based case-control study in Shanghai, China. Cases are newly diagnosed NHL patients at 29 hospitals in Shanghai. For each case, two matched controls are selected among patients without any lymphatic or hematopoietic diseases at the same hospital. Demographic, employment, medical and lifestyle information is obtained through questionnaires (primary and secondary). Sources for benzene exposure information include a database of 50,000+ benzene measurements maintained by the Shanghai Municipal Institute of Public Health Supervision (IPHS), Shanghai District IPHS, walk-through surveys at factories, additional measurements at factories and reports in Chinese medical journals. Patient enrollment started in 2003 and it is estimated that the study will have 400–450 NHL cases by December 2006. Some of the occupations or industries reported among enrolled study subjects (cases and controls) with potential exposure to benzene include shoe workers, painters, mechanics or machinists, and printers. Some of the unique features of the study are discussed.

Re: Effect of follow‐up time on risk estimates: A longitudinal examination of the relative risks of leukemia and multiple myeloma in a rubber hydrochloride cohort, Am J Ind Med 42:481–489, 2002

Re: Effect of follow‐up time on risk estimates: A longitudinal examination of the relative risks of leukemia and multiple myeloma in a rubber hydrochloride cohort, Am J Ind Med 42:481–489, 2002

Reconstruction of Benzene Exposure for the Pliofilm Cohort (1936-1976) Using Monte Carlo Techniques

The current cancer slope factor and occupational standards for benzene are based primarily on studies of the rubber hydrochloride (Pliofilm) workers. Previous assessments of this cohort by Rinsky et al. (1981, 1987), Crump and Allen (1984), and Paustenbach et al. (1992) relied on different assumptions about the available industrial hygiene data and workplace practices and processes over time, thereby yielding significantly different estimates of annual benzene exposures for many jobs. Given the inherent limitations and uncertainties involved in estimating historical exposures for this cohort, a probabilistic approach was used to better characterize their likely degree of benzene exposure. Ambient air exposures to benzene were based, in part, on the distribution of air sampling data collected at the Pliofilm facilities and assumptions about how workplace concentrations probably decreased over time as the threshold limit value (TLV) was lowered. The likely uptake of benzene from dermal exposures was estimated based on probability distributions for several exposure factors, including surface area, contact rate and duration, and skin absorption. The assessment also quantitatively accounts for improved engineering controls, extended work hours, incomplete Pliofilm production, and the use and effectiveness of respirators over time. All original data and assumptions are presented in this assessment, as is all new information obtained through additional interviews of former workers. Estimated benzene exposures at the 50th and 95th percentiles are reported as equivalent 8-h time-weighted average (TWA) airborne concentrations for 13 job categories from 1936 to 1965 (Akron I and II facilities) and 1939 to 1976 (St. Mary's facility). Data indicate that estimated equivalent airborne benzene concentrations for St. Mary's workers were highest for four job categories (Neutralizer, Quencher, Knifeman, Spreader), typically ranging from about 50 to 90 ppm during 1939-1946 (lower during 1942-1945), and 10 to 40 ppm during 1947-1976 at the 50th percentile. These estimates are 2-3 times greater than for other jobs in the Pliofilm process, and about 1.5 times less than those estimated at the 95th percentile. Estimates of equivalent airborne benzene concentrations for Akron I and II were about 1.5 times higher than for St. Mary's, but there is less confidence in these estimates, given the lack of industrial hygiene monitoring data for these facilities. Study results suggest that Paustenbach et al. (1992) generally over-estimated exposures for those job categories that had the highest exposure by about a factor of two to four. On the other hand, it was concluded that Rinsky et al. (1981, 1987) under-predicted benzene exposures for most jobs, and Crump and Allen (1984) both under- and overpredicted benzene exposures, depending on the specific job category and time period. The new estimates presented in this analysis incorporate what is considered to be the most likely range of plausible exposure values, and, accordingly, provide a better characterization of the potential workplace exposures for this cohort. These data could be combined with current or future mortality information to calculate a new cancer potency factor or occupational health standard for benzene.

Effect of follow-up time on risk estimates: a longitudinal examination of the relative risks of leukemia and multiple myeloma in a rubber hydrochloride cohort.

Choice of follow-up time for an occupational cohort can influence risk estimates. We examined the effects of follow-up time on relative risk estimates for leukemia and multiple myeloma in a cohort of 1,845 rubber hydrochloride workers. We generated standardized mortality ratios (SMRs) for yearly follow-ups, beginning each study in 1940 and increasing study end dates from 1950 through 1996. We used Cox proportional hazards modeling to explore the effects of follow-up time on the exposure-response relationship. The SMR for leukemia rose to 13.55 in 1961 and fell nearly monotonically to 2.47 by 1996. Cox modeling suggested interaction between cumulative exposure and time since exposure. A longer time to peak risk was seen for multiple myeloma. Because summary risk estimates change with follow-up time, exposure limits set using these estimates may not adequately protect workers. Consideration of appropriate follow-up time and use of more complex temporal models are critical to the risk assessment process.

Benzene exposure and hematopoietic mortality: A long-term epidemiologic risk assessment.

Previous studies of a cohort of rubber hydrochloride workers indicated an association between benzene exposure and excess mortality from leukemia and multiple myeloma. To determine whether risks remain elevated with increasing time since plant shutdown, we extended follow-up from 1981 through 1996. We evaluated risk using standardized mortality ratios (SMR) and generalized Cox proportional hazards regression models. Five new leukemia cases were observed in benzene-exposed white males, but the summary SMR for this group declined from 3.37 (95% CI = 1.54-6.41) to 2.56 (95% CI = 1.43-4.22). In regression models, cumulative exposure was significantly associated with elevated relative risks for leukemia mortality. Four new multiple myeloma deaths occurred, three of which were in workers judged to be unexposed. These findings reaffirm the leukemogenic effects of benzene exposure and suggest that excess risk diminishes with time.

Benzene‐Associated Leukemia and its Risk Assessment

Benzene‐Associated Leukemia and its Risk Assessment: Takashi Kaneko, et al. Department of Environmental Health, Medical University of Yamanashi—There is sufficient epidemiological evidence indicating that benzene is a human carcinogen. Although some reports suggest an association of benzene with multiple myeloma, malignant lymphoma and lymphatic leukemia, the closest association is found with the development of acute myeloleukemia. In contrast to epidemiological findings, benzene has induced a variety of tumors in tissues other than bone marrow in experimental animals. Attempts to induce acute myeloleukemia in rodents by benzene have not been fully successful until recently. While relatively low doses of benzene have been confirmed to induce chromosomal aberrations, sister chromatid exchanges and micronuclei in rats and mice, it has not been proven that similar changes occur in humans. For evaluation of the dose‐response relation of benzene‐induced leukemia, the epidemiological studies with a Pliofilm (rubber hydrochloride) cohort are considered most reliable and useful. According to recent re‐examinations of the Pliofilm cohort, it is highly possible that the past epidemiological studies with this cohort under‐estimated the benzene exposure level, and thus over‐estimated the risk of benzene toward leukemia. Many extrapolation models including a linear model, a linearized multistage model, a conditioned log‐logistic model, a quadratic model and a proportional hazards model have been used in the calculation of benzene risk. The risk values calculated so far with the Pliofilm cohort greatly differ according to the extrapolation models employed, and thus it cannot be determined which model is superior. While benzene exposure in the workplace is decreasing, petroleum containing a few percent of benzene has become an important source of benzene exposure for both industrial workers and the general population. Some reports suggest a positive association between gasoline exposure and the development of acute myeloleukemia.

Benzene exposure assessment in rubber hydrochloride workers: A critical evaluation of previous estimates

Many risk assessments for leukemia associated with benzene exposure have been based on the mortality experience of the rubber hydrochloride worker cohort. Although there have been several different historical exposure assessments proposed for this cohort, Paustenbach et al. [1992, J Tox Environ Health], recently published a new historical characterization of benzene exposures based on data previously developed by Rinsky et al. [1981, Am J Ind Med] and further modified by Crump and Allen [1984: OSHA]. Adjustments by Paustenbach et al. in the Rinsky et al. data result in retrospective benzene exposure estimates far greater than those previously reported, by an order of magnitude in many cases. Judgments made on the significance of dermal contact and interpretation of historical measurement data led Paustenbach et al. to arrive at exposure estimates for this cohort that are in conflict with what is known about the adverse effects of benzene exposure. More reasonable estimates for dermal absorption are included in this report that do not substantially affect total estimates of benzene exposure for the cohort. The exposure estimates originally presented in the Rinsky et al. article appear in concordance with data not previously reported in any analyses.

Oleochemical monographs (41)

Polyoxyethylated hydroxy benzyl oleamide has found use in lubricants to prevent adhesion in moulds during the production of vulcanizates of natural and of synthetic rubbers. Polyoxyethylated oleamide acts as a mould lubricant for synthetic rubbers, whilst polyglycol 400 dilaurate can be used to reduce the time and temperature necessary for the recovery of old vulcanizates using paraffin oil and bitumen. Anti‐fogging properties can be sustained in rubber hydrochloride films by the use of polyglycol 1500 dilaurate, and improved percentage elongation can be promoted in intimate blends of polystyrene and SBR rubbers by the inclusion of polyglycol 4000 monostearate. Polyoxyethylated sorbitan monostearate acts as an emulsifer in the emulsion polymerisation of styrene, butadiene and styrene/ butadiene copolymer rubbers, and it can perform as an anti‐static for the latter. Polyoxyethylated stearylamine can be incorporated into lubricants designed to prevent adhesion in moulds during production of vulcanizates of synthetic and of natural rubber, and rubber latexes and other aqueous dispersions of rubber can be rendered more stable by the employment of polyoxyethylated stearyl alcohol, and thus allow storage in untreated containers for long periods of time. Polyoxypropylated sorbitan monopalmitate will serve as a parting agent, releasing aid, for unvulcanized rubber and vulcanized rubber, without interfering with further bonding and coating of rubber.

Uncertainty in the estimation of benzene risks: application of an uncertainty taxonomy to risk assessments based on an epidemiology study of rubber hydrochloride workers.

This paper reviews 14 risk assessments that use the data from descriptions by Rinsky, Young, and co-workers of benzene-associated leukemias among a group of rubber hydrochloride workers in Ohio. The leukemogenic risks of benzene estimated in these assessments differ. The assessors use different assumptions (parameters, confounding factors, or formulas), which account for the differences in risk. The purpose of the review is to determine whether the major source of uncertainty in assessments of benzene risk arises from data, method, or concept. The results show that methodological differences dominate the other two potential sources with respect to impact on risk magnitude.

Uncertainty in the Estimation of Benzene Risks: Application of an Uncertainty Taxonomy to Risk Assessments Based on an Epidemiology Study of Rubber Hydrochloride Workers

Uncertainty in the Estimation of Benzene Risks: Application of an Uncertainty Taxonomy to Risk Assessments Based on an Epidemiology Study of Rubber Hydrochloride Workers

Effect of technological factors on the structure and properties of Eskaplen film material

The effect of the composition of the solvents, the concentration of the solutions, and the rate of film formation on the structure and properties of Eskaplen film material obtained on the basis of SKI-3 isoprene rubber hydrochloride has been investigated. The properties of the film material are shown to depend on the structure that develops during the film-forming process.

Dependence of the properties of synthetic isoprene rubber hydrochloride on the degree of hydrochlorination

IT ItAS been shown that by reaction of cis-1,4-polyisoprene with hydrogen chloride a hydrochloride of the rubber is formed, and this has film-forming properties [1-3]. Satisfactory physicomechanical properties are obtained when the degree of reaction is 85%, corresponding to 29% of combined chlorine [4]. For preparation of a film from polyisoprene hydrochloride it is necessary that the original rubber should be stereoregular. Attempts to obtain synthetic atactic polyisoprene hydrochloride in fihn form have been unsuccessful. The rubber, which is originally amorphous at room temperature, crystallizes during reaction with hydrogen chloride [5]. The laws governing the change in properties of the rubber during hydrochlorination have not yet been studied. This problem can be solved by a detailed study of the variation in properties of intermediate products of hydrochlorination in the transition from the amorphous rubber to the crystalline rubber hydrochloride, and this forms the subject of the present paper.

An electron microscope investigation of films of synthetic polyisoprene rubber hydrochloride

An electron microscope investigation of films of synthetic polyisoprene rubber hydrochloride

Damping transients in polymers during sorption and desorption

It has been found that sudden changes in atmospheric vapor pressure of swelling agents result in a transient increase in mechanical damping in polymers. The effect was observed on both raising and lowering the vapor pressure. The systems investigated were: cellulose (paper)–water; cellulose (paper)–ammonia; gelatin–water; nylon 66–water; cellulose acetate–acetone; poly(vinyl acetate)-acetone; rubber hydrochloride–chloroform; and polystyrene–benzene. The damping was measured with a low-frequency torsional pendulum. The results suggest that the transient damping effect is associated with diffusion processes taking place in the sample during attainment of equilibrium.

Mechanism of ozone cracking. II. Nucleation and growth of cracks in a plastic film

AbstractPartly unsaturated natural rubber hydrochloride films undergo stress cracking in ozonized oxygen. The origin of cracks and the correlation between stress distribution and rate of crack growth have now been studied. Cracks are initiated at foreign particles and/or surface fissures of microscopic dimensions. Fracture is promoted only if the shape of the incipient crack fulfils certain geometric conditions. These films become highly birefringent when stretched beyond the elastic limit; specific birefringence increases linearly with strain. It follows from stress optical studies that large plastic deformations take place ahead of the crack, whereas the film is deformed only elastically. Cut growth experiments confirm these conclusions. Fractography reveals that cracking consists mostly of a series of discontinuous events on a microscopic scale. The influence of crack length and polymer modulus on the critical stress, necessary for the onset of ozone cracking, is predictable from the Griffith criterion. The maximum stress at the tip was calculated from the observed dimensions of the crack and found to surpass the yield stress of the polymer. Mechanical brittle fracturing and ozone‐induced stress corrosion have been compared. The remaining empirical element, which determines the rate of cracking, is the rate of hardening on ozonization of the fresh surface.

The mechanism of ozone cracking. I. Ozone cracking of plastic films

AbstractStretched films from partly unsaturated natural rubber hydrochloride develop cracks and fracture in ozonized oxygen. Cracking occurs only above a minimum stress level of about 70 kg./cm.2. Ozone sensitivity increases exponentially with stress, but goes through a maximum near the yield point of the thermoplastic films. Contrary to rubbers, these high‐modulus materials do not undergo overall stress relaxation prior to fracturing induced by ozone. The rate of surface ozonization of an unstretched film is estimated gravimetrically and volumetrically; it is found to be similar to that of rubber surfaces. Physical and chemical changes of the ozonized surface are reported. Results are briefly compared with ozone attack on other (nonrubber) materials.

Permeation, solution, and diffusion of water in some high polymers

AbstractThe equilibrium sorption isotherms of water in polyethylene terephthalate, ethyl cellulose, and rubber hydrochloride have been measured at 25°C. by means of the quartz helix technique. The permeability constants and the diffusion constants have been measured on the same polymers and on polyethylene and polypropylene by the time‐lag technique of Barrer but with a modified apparatus. The solubility coefficients from the sorption measurements (values for polyethylene and polypropylene have been previously reported) are compared with those obtained as the quotient of the permeability and diffusion constants. In the case of polyethylene, polypropylene, and polyethylene terephthalate, excellent agreement between the two sets of values were obtained, but with rubber hydrochloride and ethyl cellulose the sorption values are much higher. These differences are interpreted in terms of clustering of water vapor in the film at higher relative humidities. The modified time‐lag technique showed concentration‐independent diffusion constant for all five polymers.