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Airborne N-nitrosomorpholine (0 to 27 micrograms per cubic meter) was found in two of four rubber industry factories. N-Nitrosodimethylamine was also found in two factories, but at lower levels. These findings may be relevant to the reported increased risk of certain types of cancer in rubber workers in some of the same areas where the N-nitrosomorpholine levels were highest.
Butyl rubber stoppers as compared with neoprene or black rubber stoppers significantly increased the shelf life of prereduced, anaerobically sterilized media for growth of obligately anaerobic bacteria.
Oxidative cleavage of poly(cis-1,4-isoprene) by rubber oxygenase RoxA purified from Xanthomonas sp. was investigated in the presence of different combinations of (16)O(2), (18)O(2), H(2)(16)O, and H(2)(18)O. 12-oxo-4,8-dimethyl-trideca-4,8-diene-1-al (ODTD; m/z 236) was the main cleavage product in the absence of (18)O-compounds. Incorporation of one (18)O atom in ODTD was found if the cleavage reaction was performed in the presence of (18)O(2) and H(2)(16)O. Incubation of poly(cis-1,4-isoprene) (with RoxA) or of isolated unlabeled ODTD (without RoxA) with H(2)(18)O in the presence of (16)O(2) indicated that the carbonyl oxygen atoms of ODTD significantly exchanged with oxygen atoms derived from water. The isotope exchange was avoided by simultaneous enzymatic reduction of both carbonyl functions of ODTD to the corresponding dialcohol (12-hydroxy-4,8-dimethyl-trideca-4,8-diene-1-ol (HDTD; m/z 240) during RoxA-mediated in vitro cleavage of poly(cis-1,4-isoprene). In the presence of (18)O(2), H(2)(16)O, and alcohol dehydrogenase/NADH, incorporation of two atoms of (18)O into the reduced metabolite HDTD was found (m/z 244), revealing that RoxA cleaves rubber by a dioxygenase mechanism. Based on the labeling results and the presence of two hemes in RoxA, a model of the enzymatic cleavage mechanism of poly(cis-1,4-isoprene) is proposed.
The complete sequence of the circular 101,016-bp megaplasmid pKB1 from the cis-1,4-polyisoprene-degrading bacterium Gordonia westfalica Kb1, which represents the first described extrachromosomal DNA of a member of this genus, was determined. Plasmid pKB1 harbors 105 open reading frames. The predicted products of 46 of these are significantly related to proteins of known function. Plasmid pKB1 is organized into three functional regions that are flanked by insertion sequence (IS) elements: (i) a replication and putative partitioning region, (ii) a putative metabolic region, and (iii) a large putative conjugative transfer region, which is interrupted by an additional IS element. Southern hybridization experiments revealed the presence of another copy of this conjugational transfer region on the bacterial chromosome. The origin of replication (oriV) of pKB1 was identified and used for construction of Escherichia coli-Gordonia shuttle vectors, which was also suitable for several other Gordonia species and related genera. The metabolic region included the heavy-metal resistance gene cadA, encoding a P-type ATPase. Expression of cadA in E. coli mediated resistance to cadmium, but not to zinc, and decreased the cellular content of cadmium in this host. When G. westfalica strain Kb1 was cured of plasmid pKB1, the resulting derivative strains exhibited slightly decreased cadmium resistance. Furthermore, they had lost the ability to use isoprene rubber as a sole source of carbon and energy, suggesting that genes essential for rubber degradation are encoded by pKB1.
The toxicity of different rubbers and plastics used in transfusion-giving sets has been investigated by examining their effects on (a) cultures of chick embryo tissues, (b) the oxygen uptake of guinea-pig skin tissue cultures, and (c) the growth of Str. pyogenes. The results of the laboratory tests have been compared with the incidence of thrombophlebitis after prolonged transfusions through the various materials. It was found that where the materials inhibited the growth of Str. pyogenes they were also toxic to tissue cultures, but that some materials which were toxic to tissue cultures did not inhibit bacterial growth. The assessments of the relative toxicity of the materials tested by the two tissue culture methods were in agreement. The skin respiration studies, however, gave more information on the early effects of the toxic materials. The relative toxicity of the materials as revealed by these tests could be correlated with the differences in the incidence of thrombophlebitis following intravenous infusions administered through giving-sets assembled with the materials tested. It is suggested therefore that the toxicity revealed by these tests is of clinical importance, and that tissue culture toxicity tests will prove to be of value in selecting rubbers and plastics for clinical purposes.
Exposure to potentially alkylating in a rubber factory was measured by determining thioether concentrations in urine samples collected at the end of work on a Friday. The study population consisted of the total work force (113) in the production departments of a factory, and office clerks (111) in two factories of the same company. The highest excretion of thioethers was detected in female workers in the belt department who were exposed through the palmar skin. High excretion was also found in workers exposed to air-borne contaminants in the calender department and in workers in the raw material stores and chemical mixing sections. Lower values were found in this dispatching station and in the contaminant-free offices. Urinary thioether determination appears to be a reliable and easy method of assessing the exposure to certain rubber chemicals.
A case-control study of bladder cancer was conducted in five United States rubber and tyre companies to determine if there were high-risk jobs and work areas within the industry. The study included 220 male cases of bladder cancer, of whom 107 were identified from hospital record reviews and 113 from death certificates. Each case was matched individually with two industry controls by sex, race, year of birth, and company. One control was matched additionally by year of hire and duration of employment. Comparisons of cases and controls not matched by year of hire and age of hire showed no differences for those variables, which suggests that age and calendar period of first exposure to the industry were not risk determinants. When the work histories of both cases and controls were contrasted it was found that cases were more likely than controls to have worked in milling (odds ratio (OR) = 1.91) and calender operation (OR = 2.21) jobs. The relative risk estimates for milling and calender operation both exhibited linear trends of increase with duration of exposure. Milling and calender operation jobs entail potential exposures to volatilised reaction products from heated rubber stock. A better understanding of aetiological associations with job type will require more detailed characterisation of the work environment with regard to the sources and levels of aromatic amines and other suspected bladder carcinogens.
A cross sectional prevalence study of chest pain in 94 rubber chemical workers exposed to carbon disulphide (CS2) and methaemoglobin forming aromatic amines was carried out. The purpose of the study was to determine whether the prevalence of chest pain or coronary heart disease (CHD), or both, in exposed individuals exceeded that of a group of non-exposed individuals from the same plant. Cardiovascular, smoking, and occupational histories were obtained. Blood pressure, height, weight, serum cholesterol, and fasting blood glucose were measured. Resting electrocardiograms (ECGs) were obtained on all study participants, as were exercise stress tests on selected exposed individuals. Matching eliminated important known risk factors for coronary artery disease. Both chest pain and angina were significantly related to exposure, controlling for age and cigarette smoking. This association was not dependent on duration of exposure as defined by 10 or more years of employment in the department of interest. CHD as defined by angina, a history of myocardial infarction, or a coronary ECG or a combination of these occurred more frequently among exposed workers. The number of abnormal ECGs in the exposed group was twice that in the control group, but the difference was not statistically significant. Age rather than exposure appeared to be the important variable associated with raised blood pressure. Neither biological measures of exposure nor ECGs showed an acute effect of workplace exposures on the myocardium. Possible additive or multiplicative effects of individual chemical agents could not be evaluated. Appropriate modification of medical surveillance of rubber chemical workers with exposure to CS2 and aromatic amines is warranted.
The mortality experienced by a cohort of 36445 rubber workers during 1946-80 has been investigated. These workers were all male operatives first employed in any one of the 13 participating factories in 1946-60; all had worked continuously in the industry for a minimum period of one year. Compared with the general population, statistically significant excesses relating to cancer mortality were found for cancer of the stomach (E = 245.9, O = 282, SMR = 115), primary cancer of the liver (E = 12.8, O = 22, SMR = 172), cancer of the lung (E = 892.7, O = 1191, SMR = 133), and all neoplasms (E = 2165.2, O = 2487, SMR = 115). Statistically significant deficits were found for cancer of the prostate (E = 79.7, O = 59, SMR = 74) and cancer of the testis (E = 10.3, O = 4, SMR = 39). The method of regression models in life tables (RMLT) was used to compare the duration of employment in the industry, the duration in "dust exposed" jobs, and the duration in "fume and/or solvent exposed" jobs of those dying from causes of interest with those of all matching survivors. Significant positive associations were found only for cancer of the stomach and cancer of the lung. The results of the RMLT analysis are independent of those from the SMR analysis, and the study has provided further evidence of a causal association between the risks of lung and stomach cancer and certain occupational exposures in the rubber industry.
When considering rubber tyre manufacturing from an occupational health viewpoint, three areas may be identified in which exposure to respirable materials are potentially harmful: the processing, curing, and talc areas. A study of the ventilatory function of the entire work force employed in the processing area in a rubber tyre manufacturing plant was undertaken to determine whether an acute reduction in lung function occurs over the course of their working shift (the plant worked a three shift system) and whether a chronic exposure to the occupational airborne contaminants causes permanent changes in lung function. The ventilatory function was measured at the worksite at the beginning and immediately after the end of the workshift. No evidence of chronic obstructive pulmonary disease was found and in most cases no significant decline in FEV1 was observed. Only one of the 79 individuals showed a moderate obstruction, measured by the ratio FEV1/FVC which gave the value of 0.55, with no variation over the shift. For non-smokers, the FVC, FEV1, and FEF25-75% were lower in those exposed for more than five years than in those exposed for five years or less. A similar pattern was also observed in the FVC and FEV1 of the smokers. None of these differences was statistically significant. Within each exposure group the pulmonary function of the smokers was lower than that of the non-smokers, but the only significant difference was found in the values of FEF25-75%. Only one man showed a decline in the FEV1/FVC ratio over the shift, but during each shift, a decrease in all the lung function tests was observed. The decrease was smallest during the first of the three shifts. These results are thought to support the hypothesis that there are acute adverse effects over an eight hour shift. Further investigations are needed to discover whether these acute changes in lung function result from a chemical stimulation or irritant receptors in the airways.
The purpose of the study was to describe the mortality experience of an Italian cohort of rubber workers and an attempt was made to identify any occupational cancer hazards that might currently be affecting men employed in this type of work. A total of 4917 male workers who first started working in a large rubber factory between 1962 and 1972 have been followed up until 31 January 1983. The number of deaths from all causes and from malignant neoplasms was determined and compared with the expected number of deaths calculated from mortality rates for the province in which the population of the plant lived. Mortality from all causes was 85% of that expected. A slight overall excess of deaths from cancer (SMR = 119) was found; this was entirely due to the excess mortality in the 35-44 age group. In order further to evaluate the possible existence of a cancer risk SMRs were analysed by duration of exposure, time since first exposure, and for specific sites of cancer. A trend in SMR with duration of exposure was found for employees with 10 years of follow up or more. A high risk for some tumour sites emerged.
The mortality experienced by a cohort of 36,691 rubber workers during 1946-85 has been investigated. These workers were all male operatives first employed in any one of the 13 participating factories in 1946-60; all had worked continuously in the industry for a minimum period of one year. Compared with the general population, statistically significant excesses relating to cancer mortality were found for cancer of the pharynx (E = 20.2, O = 30, SMR = 149), oesophagus (E = 87.6, O = 107, SMR = 122), stomach (E = 316.5, O = 359, SMR = 113), lung (E = 1219.2, O = 1592, SMR = 131), and all neoplasms (E = 2965.6, O = 3344, SMR = 113). Statistically significant deficits were found for cancer of the prostate. (E = 128.2, O = 91, SMR = 71), testis (E = 11.0, O = 4, SMR = 36), and Hodgkin's disease (E = 26.9, O = 16, SMR = 59). Involvement of occupational exposures was assessed by the method of regression models and life tables (RMLT). This method was used to compare the duration of employment in the industry, the duration in "dust exposed" jobs, and the duration in "fume and/or solvent exposed" jobs of those dying from causes of interest with those of all matching survivors. Positive associations (approaching formal levels of statistical significance) were found only for cancers of the stomach and the lung. The results of the RMLT analysis are independent of those from the SMR analysis, and the study continues to provide limited evidence of a causal association between the risks of stomach cancer and dust exposures, and the risks of lung cancer and fume or solvent exposures in the rubber industry during the period under study.
A cohort of 1624 employees (957 men, 667 women) in a rubber factory in Shanghai have been followed up since 1972 and their 12 year mortality experience is presented. The relative risk of lung cancer for smokers was 8.5 for men and 11.4 for women and for rubber workers exposed to curing agents or talc powder 3.2 for men and 4.6 for women.
An analysis of the mortality of a cohort of 6629 workers employed from 1906 to 1981 in a rubber tyre factory in northern Italy (978 deaths and over 133,000 man-years at risk) showed that the all cause mortality ratio was slightly lower than expected (0.91). Overall cancer mortality was close to expected (275 v 259.4) but there were significant excess rates for two cancer sites: pleura (9 observed v 0.8 expected, which may be due to the use of fibre containing talc) and bladder (16 observed v 8.8 expected). Death rates were not raised for other sites previously associated with employment in the rubber industry, such as cancers of the lung and brain, leukaemias, or lymphomas. The substantially reduced relative risk of pleural cancer among workers first employed after 1940 (RR = 0.05 compared with before 1940) probably reflected improvements in working conditions over more recent periods. For cancer of the bladder, the relative risk was also lower for workers first engaged after 1940. Thus no appreciable risk for any disease was apparent for workers employed over the past four decades. Analysis for each of the 27 job categories showed a substantial excess for cancer of the pleura in the mechanical maintenance workers (4 observed v 0.17 expected); an excess of cancer of the lung (21 v 13.48) was also present in this job category.
Four species of bacteria capable of CH4 fermentation of rubber latex effluent were isolated and identified as a Methanococcus, a strain of M. vannielii, a Methanobacterium and a strain of M. omelianskii. Auxanographic tests using the four strains showed growth and CH4 formation on a basal medium containing mineral salts or added H2 and Co2. Varied response was obtained when the basal medium was added to formate, acetate, butyrate, methanol, ethanol, and glucose. Previous work has established acid fermentation of Hevea latex arising from bacterial contamination and decomposition of the non-rubber constituents which consist of N-compounds, 2% quebrachitol, and smaller concentration of carbohydrates. This suggests that reduction of CO2 and fermentation of acids formed during metabolism of Hevea latex are possible pathways of CH4 production.
A thin-layer chromatographic method was used to highlight the leaching into drug preparations of several constituents of elastomeric closures. Among the 150 preparations analysed, the twenty-eight local anaesthetics presented in single-dose delivery syringe-cartridges, one Epinephrine injection in prefilled syringes, eight insulin preparations and two Prednisolone acetate suspensions in the form of small volume flasks (less than or equal to 20 ml) were contaminated by one or more of the following: 2-mercaptobenzothiazole (MBT), 2-mercaptobenzothiazole disulphide and 2-mercaptobenzimidazole (MBI). Prednisolone acetate suspensions also contained 2,2'-methylene-bis(4-methyl-6-alpha-methylcyclohexylphenol). No contamination was found in drug preparations presented in large volume flasks (250-1000 ml). 2-(2-Hydroxyethylthio)-benzothiazole was not present, which indicated that the rubbers had not been sterilized with ethylene oxide. Elastomeric parts of drug closures analysed in the same way contained the same compounds as those found in drugs, one case excepted, which confirms the origin of the contamination. The lowest and the highest concentrations were found in syringe-cartridges; they ranged from 8.3 to 13.8 micrograms ml-1 for MBT, from 2.9 to 9.3 micrograms ml-1 for MBTS and from 2.8 to 11.1 micrograms ml-1 for MBI. Variable results were obtained, for a same preparation, depending upon the batches analysed, which indicates that rubber formulations and/or vulcanization conditions differed. The allergenic, toxic, embryotoxic and mutagenic properties of the compounds leached are discussed.
We developed a method involving air-drying of a rubber suspension after fixation in glutaraldehyde-tannic acid and postfixation in osmium tetroxide for SEM observation. For TEM immunolabeling the suspension was air-dried after osmium-only fixation. Whereas conventional methods failed to satisfactorily stabilize rubber particles, the methods described here proved successful in preserving their integrity.
The 'rubber-hand' illusion, in which individuals misattribute tactile sensations felt by their hand to a rubber prosthetic hand that they see being stimulated, was employed to examine the relationship between perceptual body image and unhealthy body change in 128 volunteers. Variance in unhealthy body development in males (22%) and in bulimic symptomatology in both females and males (10%), was explained by susceptibility to the illusion. The illusion, which is relatively free from cognitive and emotional 'contamination', could be used to identify individuals most responsive to therapies designed to correct inaccurate body perceptions-individuals whose perceptual body image is malleable.