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Bladder cancer in rubber workers. Do screening and doctors' awareness distort the statistics?

The use of recognised carcinogens in the rubber industry before 1950 led to the introduction of screening progammes offering urinary cytology to workers who had been exposed. Publicity given to the introduction of these programmes and to individual claims for compensation have increased medical practitioners' awareness of a relationship between work and the industry and the subsequent development of bladder cancer. In this study 27 rubber workers and 88 controls registered in 1966 and 1967 with bladder cancer have been followed. A comparison of their death-rates and of the relative frequency of bladder cancer recorded on the death certificates should indicate whether cytological screening or doctors' awareness might explain a recent rise in the bladder-cancer death-rate in this industry. Since the proportions of rubber workers and controls who died before 1976 were similar (74% and 73% respectively) and bladder cancer was mentioned with similar frequence on their death certificates (80% and 83% respectively) neither screening nor doctor's awareness would appear to have an important influence.

Adenocarcinoma↗

Determination of the sensitising activity of the rubber contact sensitisers TMTD, ZDMC, MBT and DEA in a modified local lymph node assay and the effect of sodium dodecyl sulfate pretreatment on local lymph node responses.

A modified local lymph node assay (LLNA) was used to determine the sensitising activity of four chemicals used for the production of natural rubber latex products. Tetramethylthiuramdisulfide (TMTD), 2-mercaptobenzothiazole (MBT) and zincdimethyldithiocarbamate (ZDMC), three moderate human sensitisers, and diethylamine (DEA) a known human sensitiser, were epicutaneously administered on the ear and the proliferating activity in the draining (auricular) lymph node (LN) was determined by ex vivo (3)H-thymidine incorporation. Consistent results were obtained for TMTD and ZDMC with stimulation indices (SI) above 3, identifying these compounds as sensitiser, while for DEA and MBT inconsistent results were obtained. For all parameters determined such as LN weight, LN cell number, cell proliferation per 2 x 10(6) cells, and cell proliferation per LN statistical significant increases were observed. The SI, expressed as cellular proliferation per LN or per animal (left and right LN combined), was the most sensitive parameter with an optimum at day 5 after start of treatment.Furthermore, we investigated whether the use of sodium dodecyl sulfate (SDS) was able to enhance weak responses in the LLNA. SDS treatment with dosages of 10% and higher resulted in a SI above 3, while a dosage of 1% SDS showed no activity. Pretreatment with 1% SDS 1 h before application of the rubber chemicals enhanced the responses to these chemicals consistently, identifying also DEA and MBT as sensitisers. Our results indicate that SDS had synergistic activity on the LN responses of the administered rubber chemicals in the LLNA. For the moderately responding sensitisers TMTD and ZDMC both IFN-gamma and IL-4 production was observed. For the weakly responding sensitisers DEA and MBT both IFN-gamma and IL-4 cytokine production was only observed after pretreatment of the animals with 10% SDS. For 10% and 20% SDS, inducing approximately a SI of 20 in the LLNA, no induction of cytokines was observed.

Allergens↗

Prevalence of skin test reactions to natural rubber latex in hospital personnel in Russia and eastern Europe.

BACKGROUND: Allergic reactions to natural rubber latex have increased during the past 10 years, especially in many health care workers (HCWs) who have high exposure to latex allergens. The prevalence of skin test reactions to natural rubber latex in Russia, the Commonwealth of Independent States (CIS), and eastern Europe is unknown. OBJECTIVE: The purpose of this study was to determine the prevalence of skin test reactivity to natural rubber latex in a population of HCWs exposed to latex. METHODS: Nine hundred one HCWs regularly exposed to latex were evaluated using an allergy history questionnaire. Subjects were tested for latex allergy by titrated skin prick test with a biologically standardized latex extract. The diagnosis of latex allergy was defined by the presence of clinical symptoms when exposed to latex along with a positive skin prick test to latex. RESULTS: Forty-nine (5.4%) HCWs were skin test-positive to latex. Seventeen (1.9%) HCWs were classified as latex-allergic based upon positive skin tests to latex associated with allergy symptoms with exposure. Seven of 901 HCWs had experienced anaphylactic reactions to latex. The most frequently reported symptom related to latex exposure was contact urticaria. CONCLUSIONS: The prevalence of latex allergy among HCWs in Russia, the CIS, and adjacent eastern European countries is considerably less than reported in HCWs exposed to latex in western Europe and the United States. The low prevalence of latex allergy in Russia and the CIS suggests that lessened exposure to natural latex powdered gloves may diminish the prevalence of latex sensitization in HCWs in Russia and the CIS.

Adolescent↗

Measurement of natural rubber proteins in latex glove extracts: comparison of the methods.

BACKGROUND: Health care workers and individuals with frequent contact with latex are at risk for latex protein allergy. OBJECTIVE: The purpose of this study was to compare several established methods for measuring protein in extracts from latex-containing medical devices. METHODS: Extracts from latex gloves were analyzed for natural rubber proteins using a modified Lowry assay and two different immunochemical assays. The immunochemical methods were competitive inhibition assays that employed either immune rabbit serum or human serum with antibodies directed against natural rubber proteins. RESULTS: Seventy extracts representing five different brands of gloves from four manufacturers were analyzed. A good linear correlation (R = 0.88) was found between the immunoassay methods. Correlation to the modified Lowry method was not possible because many of the samples were below the limit of detection for the Lowry assay. Reference extracts and antisera were further characterized by Western blot analysis. The data demonstrate that the proteins recognized by rabbit antisera and the proteins recognized by human IgE are similar. The greatest difference in the immunochemical assays appears to be the relative binding of the antibody sources to high and low molecular weight natural rubber proteins in the reference extracts. CONCLUSIONS: The immunochemical assays are specific for latex proteins and provide a more sensitive and biologically relevant method for determining protein levels in latex medical products.

Animals↗

Mutagenic exposure in the rubber manufacturing industry: an industry wide survey.

Mutagenic exposure conditions in several rubber manufacturing companies (n=9) in The Netherlands were studied. Mutagenicity of total suspended particulate matter in air (TSPM) and of wipe samples from possible contact surfaces were measured in the Ames mutagenicity assay with Salmonella typhimurium YG1041 in the presence of a metabolic activation system. Large differences in median mutagenicity of TSPM samples were observed between companies (range 49-1056rev/m(3)) and to a lesser extent between production functions (range 129-402rev/m(3)). The production function curing revealed overall the highest TSPM mutagenicity levels. Forty-one percent of the surface wipe samples revealed mutagenic activity ranging from 26 to 665rev/cm(2). Mixing had the largest proportion of positive samples resulting in a median surface mutagenic contamination of 39rev/cm(2). Surface mutagenic contamination, averaged per department/company combination, showed only a weak correlation with TSPM mutagenicity (r=0.28, P=0.05). Company, production function and total soluble matter (e.g. mass collected upon extraction with organic solvents with different polarity) explained 79 and 81% of the variability in mutagenicity of TSPM and surface contamination levels, respectively. "Company" was identified as the most important exposure determinant for mutagenic activity in TSPM and surface wipe samples. This indicates the importance of company specific determinants like production volume and rubber chemicals used for the encountered mutagenic exposure conditions. Detection of substantial mutagenic activity on possible contact surfaces supports furthermore the potential importance of the dermal route in the uptake of genotoxic compounds of workers in the rubber manufacturing industry.

Air Pollutants, Occupational↗

Monitoring airborne genotoxicants in the rubber industry using genotoxicity tests and chemical analyses.

This research was designed to examine the presence of mutagenic/carcinogenic compounds in airborne pollutants in the rubber industry using an integrated chemical/biological approach. Inhalable airborne particulate matter (PM-10: <10 microm) was collected in four rubber factories using a high-volume sampler equipped with a cascade impactor for particle fractionation. The organic extracts of two different fractions (0.5-10 microm and <0.5 microm) were examined for mutagenicity with the Ames test and for in vitro DNA-damaging activity in human leukocytes by single-cell microgel electrophoresis (Comet assay). The extracts were also studied by gas chromatography/mass spectrometry (GC/MS) for polycyclic aromatic hydrocarbon (PAH) content. Nitrosamines in ambient air were sampled on cartridges and analysed by GC with a thermal energy analyser (TEA) detector. Airborne volatile genotoxins were monitored in situ using a clastogenicity plant test (Tradescantia/micronuclei test). The results showed that airborne particulates were mainly very fine (<0.5 microm) and that trace amounts of genotoxic nitrosamines (N-nitrosodimethylamine: 0.10-0.98 microg/m(3); N-nitrosomorpholine: 0.77-2.40 microg/m(3)) and PAH (total PAH: 0.34-11.35 microg/m(3)) were present in air samples. Some extracts, particularly those obtained from the finest fractions, were mutagenic with the Ames test and genotoxic with the Comet assay. In situ monitoring of volatile mutagens using the Tradescantia/micronuclei test gave positive results in two working environments. The results showed the applicability of this integrated chemical-biological approach for detecting volatile and non-volatile genotoxins and for monitoring genotoxic hazards in the rubber industry.

Air Pollutants, Occupational↗

Structural characterization of alpha-terminal group of natural rubber. 2. Decomposition of branch-points by phospholipase and chemical treatments.

The treatment of deproteinized natural rubber (DPNR) latex with phospholipases A(2), B, C, and D decreased significantly the long-chain fatty acid ester contents in DPNR and also the molecular weight and Higgins' k' constant, except for phospholipase D treatment. This indicates the presence of phospholipid molecules in NR, which combine rubber molecules together. Transesterification of DPNR resulted in the decomposition of the functional group at the terminal chain-end (alpha-terminal), including phospholipids and formed linear rubber molecules. The addition of small amounts of ethanol into the DPNR solution reduced the molecular weight and shifted the molecular weight distribution (MWD) comparable to that of transesterified DPNR (TE-DPNR). The addition of diammonium hydrogen phosphate into DPNR-latex in order to remove Mg2+ ions yielded a slight decrease in molecular weight and a slight shift in MWD. The phospholipids are expected to link with mono- and diphosphate groups at the alpha-terminal by hydrogen bonding and/or ionic linkages. The decrease in the molecular weight and Huggins' k' constant of DPNR demonstrates the formation of linear molecules after decomposition of branch-points by this treatment, showing that phospholipids participate in the branching formation of NR. The branch-points formed at the alpha-terminus are postulated to originate predominantly by the association of phospholipids via micelle formation of long-chain fatty acid esters and hydrogen bonding between polar headgroups of phospholipids.

Esterification↗

Characterization of gaseous and solid product from thermal plasma pyrolysis of waste rubber.

Pyrolysis of waste rubber in thermal plasma is studied for the purpose of producing gaseous fuel and recovering carbon black filler. The plasma reactor has a dc arc nitrogen plasma generator with a maximum electric power input of 62.5 kVA and a reaction chamber of 50 mm inner diameter and 1000 mm height. The results of a series of experiments have shown that the main components of the gaseous product are H2, CO, C2H2, CH4, and C2H4; the heat value of the gas is about 5-9 MJ/Nm3. The solid product contains more than 80 wt % elemental carbon, has a surface area of about 65 m2/g, and is referred to as pyrolytic carbon black (CBp). X-ray photoelectron spectroscopy (XPS) analysis has revealed that the CBp has mainly graphitic carbon structure similar to those of commercial carbon black. The CBp may be used as semireinforcing carbon black in nontire rubber applications, or, after upgrading, as carbon black filler for tire. Thus thermal plasma pyrolysis is potentially a useful way of treating waste rubber for resource recovery.

Air Pollutants↗

Combination of ultrasound and discarded tire rubber: removal of Cr(III) from aqueous solution.

Ground discarded tire rubber is an interesting and inexpensive medium for the sorption of toxic metals, including chromium, from water. The batch sorption tests were conducted to investigate the sorption capacity of Cr(III) from aqueous solution by ground tire in the presence and absence of ultrasound. The research parameters included ultrasonic waves, solution temperature, aqueous chromium concentration, particle size of the ground tire, contact time, and others. The Langmuir model was applied to the sorption equilibrium to determine the maximum metal sorption capacity in the presence and absence of ultrasound. The Langmuir constants were also obtained from the isotherms under different conditions. The results indicated that the tire rubber was a more efficient sorbent for the removal of chromium in the presence of ultrasound. Because there are several stages in the sorption process, it is important to find out which step or steps control the rate of sorption. According to the results, the internal porous diffusion is the rate-controlling step. The diffusion coefficient of Cr(III) in ground tire rubber in the presence of ultrasound was about two times greater than that in the absence of ultrasound. The effect of ultrasound on the sorption process could be explained by the thermal and nonthermal properties of acoustic cavitation.

Absorption↗

The use of rubber dam in the UK. A survey.

The purpose of this survey was to determine the frequency of use of rubber dam isolation in the United Kingdom for both operative and endodontic procedures. Questionnaires were sent to 1800 dentists throughout the country, with 1008 returns (56%). Most replies were from dentists active in general dental practice. The use of rubber dam is largely neglected and more than 70% of all dentists surveyed did not utilise rubber dam for any procedure whatsoever.

Age Factors↗

Endodontics: Part 6 Rubber dam and access cavities.

Rubber dam is easy to apply once the basic components and principles are understood. An efficient and well-trained dental nurse will greatly facilitate the application procedure. Although preparation of the access cavity may be commenced before rubber dam is applied to enable anatomical landmarks to be followed, the rubber dam should be placed as soon as possible with adequate protection against contamination of the access. The access cavity reflects the shape of the pulp chamber, modified by the angle of instrument approach.

Dental Auxiliaries↗

Patients' attitudes to rubber dam.

AIM: The aims of this study were to record patients' views of their experience of RD use in an objective manner, and to evaluate the influence of some personal and clinical factors on patients' opinion. METHODOLOGY: A questionnaire was designed which was then distributed to patients receiving dental treatment under RD by (a) final-year dental students at Birmingham Dental School, and (b) general dental practitioners. Patients completed the confidential questionnaire anonymously after treatment, outside the treatment room. After 100 correctly completed forms were collected from group (a) and 106 from group (b), data were entered into a database and subsequently analyzed using SPSS. Analyses were confined to simple cross-tabulations of the patients' responses and potential associated factors, with chi-square analysis and appropriate follow-up comparisons wherever necessary. RESULTS: In both groups, the majority of patients said they would prefer RD to be used at their next appointment, and most had a positive opinion of the experience. No statistically significant association between age, sex, procedure, application time or duration of use and preference for rubber dam was found. Prolonged RD use showed some association with a negative opinion of the experience of RD. Compared with the dentists, students took longer to apply rubber dam and it was in place for longer. Fewer student patients preferred RD next time, and were less positive about its use than the dentists' patients. CONCLUSIONS: Further evidence is presented that (i) Patients generally are not averse to RD. (ii) Placement of rubber dam does not take long. (iii) Operator experience improves patient compliance.

Adolescent↗

Allergens and natural rubber proteins.

BACKGROUND: Allergy to natural rubber latex (NRL) results from exposure to proteins derived from Hevea brasiliensis. Type I latex hypersensitivity is observed in certain occupational and other high-risk groups with frequent exposure to NRL products. This includes health care workers (HCWs), workers in the latex industry, children with spina bifida, and atopic individuals. OBJECTIVES: Early reliable diagnosis and avoidance are required for better patient care. Standardized reagents are not presently available for in vitro and in vivo testing and treatment of patients with latex allergy. However, a number of allergens have been isolated and characterized from Hevea latex and NRL products. Currently, a total of 11 major and minor allergens are designated by the International Allergen Nomenclature Committee. This article reviews the structural and functional characteristics of these latex allergenic proteins. RESULTS: NRL-allergenic proteins include those involved in the biosynthesis of polyisoprene and coagulation of latex rubber elongation factor, small rubber particle protein, prohevein, and patatin. Pathogenesis-related proteins include beta-1,3-glucanases, chitinases, and hevamine; and the structural proteins include microhelix protein complex, proline-rich protein, profilins, enolases, and manganese superoxide dismutase. Recombinant allergens demonstrated skin test reactivity in patients with latex allergy. The minimal level of skin test reactivity was about 70 pg/mL for NRL and 1 ng/mL for recombinant allergens. The use of selected recombinant latex allergens (Hev b 5, Hev b 6, and Hev b 7) in skin prick tests identified 93% of allergic individuals, mainly health care workers. CONCLUSIONS: Recombinant latex allergens are clinically reactive and can be produced in a standardized manner, which could potentially provide safe and sensitive reagents for the diagnosis and treatment of type I latex allergy.

Allergens↗

Clinical and laboratory-based methods in the diagnosis of natural rubber latex allergy.

The accurate diagnosis of hypersensitivity to natural rubber latex is the initial step in the effective management of individuals with latex allergy and in ensuring the quality of epidemiologic studies. The diagnostic algorithm used in the evaluation of an individual with suspected latex allergy begins with a comprehensive clinical history during which risk factors (atopy, food allergies, hand dermatitis) and temporal relationships between symptoms and natural rubber product exposure are identified. If type IV hypersensitivity is suspected because of the delayed nature (hours to days) and confinement of symptoms to the skin-latex product contact areas, patch testing can be conducted to confirm the presence of activated T cells with specificity for rubber chemicals. If type I hypersensitivity is suspected because of ocular, upper and lower airway, and/or systemic symptoms that have rapid onset (minutes) after a definable latex exposure, a confirmatory skin or blood test for IgE antibody may be conducted to verify a state of sensitization within the individual. The definitive diagnosis would then be made only after consideration of the individual's clinical history and confirmatory in vivo and/or in vitro laboratory test results. If discordance remains between highly convincing latex-associated symptoms as identified in the history and repetitively negative confirmatory IgE antibody test results, then one of several types of in vivo provocation tests may be performed for adjudication. This overview examines the current state of the art in both in vivo and in vitro diagnostic methods for latex-specific IgE antibody detection in skin and blood. The performance, advantages, and limitations of each diagnostic method are compared.

Algorithms↗

Leukemia mortality and occupational exposure to rubber: a nested case-control study.

OBJECTIVE: The excess risk of leukemia in rubber industry was considered to be real and attributed to the exposure to solvents, particularly benzene. METHODS: Following a nested case-control study, we used the data of 7 leukemia deaths in 1973-1997 and 28 controls matched for sex and age from the same cohort of a rubber plant. Leukemia risks due to exposure to rubber were assessed, unadjusted and adjusted for non-occupational factors by conditional logistic regression. RESULTS: OR for leukemia was found to be 7.81 (95% CI = 0.77-78) in grouped analysis for one or more years of work in the inner tire tube department. The models for continuous exposure variables indicated that working for one year in the inner tire tube department was associated with a 10 percent increment in the OR (95% CI = 1.00-1.24; score test for linear trend: chi 1(2) = 6.27, P = 0.012). The confounding effects studied could not be ruled out for the excess risks. No excess risk was found in the remaining four departments. CONCLUSIONS: Because of widespread exposure to various carcinogens in the process of making inner tire tubes, removal of a single agent (benzene) may not eliminate the risk of leukemia in the entire industry.

Adult↗

Elevated serum IgE, eosinophilia, and lung function in rubber workers.

We previously reported an outbreak of acute respiratory illness associated with eosinophilia in a group of rubber workers who performed a thermoinjection process in which synthetic rubber was heated and then injected onto metal molds. This study was conducted to determine if persistent respiratory health effects were associated with this work area and to explore the possible allergic etiology of this syndrome. A survey was performed 1 mo after a major improvement in area ventilation and consisted of baseline, cross-shift, and cross-week spirometry; diffusing capacity; serum immunoglobulin E (IgE), total eosinophil count; and skin patch testing. Baseline lung function, cross-shift, and cross-week spirometry were not significantly worse in the exposed group as compared to the control group. However, either eosinophilia (greater than 450/mm3) or elevated serum IgE (greater than 470 ng/ml) were present in 44% of exposed workers vs. 11% of the control group (p = .003). Nine months later, neither eosinophilia nor elevated IgE were associated with employment in this work area. We conclude that employment in the thermoinjection process was associated with eosinophilia and elevated IgE, which suggests sensitization to one of the components of the rubber, although no effect on pulmonary function could be demonstrated.

Adult↗

Development and application of an LC-MS method to determine possible migration of mercaptobenzothiazole, benzothiazole and related vulcanization residues from rubber used in contact with food and drink.

A method was developed for the analysis of food and drink for residues of specific vulcanization accelerators used to cross-link rubber. The method was applied to the analysis of 236 samples of selected retail foodstuffs that may have been in contact with rubber during their manufacture, transport and storage. The method of analysis involved extraction of the food using acidified solvent and analysis by liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry (LC-APcI-MS). The detection limit depended on the sample type and was in the range 0.005-0.043 mg kg(-1) for 2-mercaptobenzothiazole (MBT) and benzothiazole (BT). The average analytical recovery rate was 82% for MBT and 87% for BT. The analytical method was validated using a blind check sample exercise. For MBT and BT at seven different concentrations in the range 0.1-0.2 mg kg(-1), the laboratory found a mean of 91 and 90% of the expected concentrations, respectively. No trace of MBT or BT was found in any of the retail samples. It is also concluded that no sample contained significant 2-mercaptobenzothiazyl disulphide (MBTS) or N- cyclohexyl-2-benzothiazole sulphenamide (CBS). Both MBTS and CBS are important accelerators used to vulcanize rubber and they break down in foodstuffs to form MBT and BT. The absence of MBT and BT in the foodstuffs therefore also provides proof of the absence of MBTS and CBS.

Benzothiazoles↗

Estrogenic activities of chemicals related to food contact plastics and rubbers tested by the yeast two-hybrid assay.

Food contact plastics and rubbers possibly contain many kinds of chemicals such as monomers, oligomers, additives, degradation products of polymers and additives, and impurities. Among them, bisphenol A, nonylphenol, benzylbutyl phthalate, styrene oligomers and hydroxylated benzophenones have been reported to possess estrogenic activities. In this study, other chemicals related to food contact plastics and rubbers, and their metabolites induced by the S9-mixture were tested for their estrogenic activities using the yeast two-hybrid assay. Among the 150 chemicals, 10 chemicals such as bis(4-hydroxyphenyl) methane, 4-cyclohexylphenol, 4-phenylphenol, 4,4'-isopropylidenediphenol alkylphosphite, two type of styrenated phenol (including mono type), tris(nonylphenyl) phosphite, 2,2'-dihydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone and 2,4-diphenyl-4-methyl-1-pentene, their metabolites and the metabolites of 6 other chemicals, such as 2-(phenylmethyl) phenol, styrenated phenol (di and tri type), 1-(N-phenylamino)naphthalene, 4-tert-butylphenylsalicylate, nonylphenol ethoxylates and 2-methyl-6-tert-butylphenol, displayed estrogenic activities. All of them contained a phenol group in their chemical structures or formed one easily by hydrolysis or metabolism. However, most of the chemicals related to food contact plastics and rubbers, and their metabolites did not show any estrogenicity.

Antioxidants↗