Controlling C2C12 Cytotoxicity on Liquid Metal Embedded Elastomer (LMEE).

Liquid metal embedded elastomers (LMEEs) are highly stretchable composites comprising microscopic droplets of eutectic gallium-indium (EGaIn) liquid metal embedded in a soft rubber matrix. They have a unique combination of mechanical, electrical, and thermal properties that make them attractive for potential applications in flexible electronics, thermal management, wearable computing, and soft robotics. However, the use of LMEEs in direct contact with human tissue or organs requires an understanding of their biocompatibility and cell cytotoxicity. In this study, the cytotoxicity of C2C12 cells in contact with LMEE composites composed of EGaIn droplets embedded with a polydimethylsiloxane (PDMS) matrix is investigated. In particular, the influence of EGaIn volume ratio and shear mixing time during synthesis on cell proliferation and viability is examined. The special case of electrically-conductive LMEE composites in which a percolating network of EGaIn droplets is created through "mechanical sintering" is also examined. This study in C2C12 cytotoxicity represents a first step in determining whether LMEE is safe for use in implantable biomedical devices and biohybrid systems.

Results from a round robin test for the ecotoxicological evaluation of construction products using two leaching tests and an aquatic test battery.

A European round robin test according to ISO 5725-2 was conceptually prepared, realised, and evaluated. The aim was to determine the inter-laboratory variability of the overall process for the ecotoxicological characterization of construction products in eluates and bioassays. To this end, two construction products BAM-G1 (granulate) and HSR-2 (roof sealing sheet), both made of EPDM polymers (rubber), were selected. The granular construction product was eluted in a one stage batch test, the planar product in the Dynamic Surface Leaching test (DSLT). A total of 17 laboratories from 5 countries participated in the round robin test: Germany (12), Austria (2), Belgium (1), Czech Republic (1) and France (1). A test battery of four standardised ecotoxicity tests with algae, daphnia, luminescent bacteria and zebrafish eggs was used. As toxicity measures, EC50 and LID values were calculated. All tests, except the fish egg test, were basically able to demonstrate toxic effects and the level of toxicity. The reproducibility of test results depended on the test specimens and the test organisms. Generally, the variability of the EC50 or LID values increased with the overall level of toxicity. For the very toxic BAM-G1 eluate a relative high variability of CV = 73%-110% was observed for EC50 in all biotests, while for the less toxic HSR-2 eluate the reproducibility of EC50 varied with sensitivity: it was very good (CV = 9.3%) for the daphnia test with the lowest sensitivity, followed by the algae test (CV = 36.4%). The luminescent bacteria test, being the most sensitive bioassay for HSR-2 Eluate, showed the highest variability (CV = 74.8%). When considering the complex overall process the reproducibility of bioassays with eluates from construction products was acceptable.

1,3-Butadiene, styrene and lymphohematopoietic cancer among male synthetic rubber industry workers--Preliminary exposure-response analyses.

We updated the mortality experience of North American synthetic rubber industry workers to include follow-up from 1944 through 2009, adding 11 years of mortality data to previous investigations. The present analysis used Cox regression to examine the exposure-response relationship between 1,3-butadiene (BD) and styrene (STY) parts per million (ppm)-years and leukemia (N = 114 deaths), non-Hodgkin lymphoma (NHL) (N = 89) and multiple myeloma (MM) (N = 48). A pattern of largely monotonically increasing rate ratios across deciles of BD ppm-years and a positive, statistically significant exposure-response trend were observed for BD ppm-years and leukemia. Using continuous, untransformed BD ppm-years the regression coefficient (ß) adjusted only for age was 2.6 × 10(-4) (p < 0.01); the regression coefficient adjusted for age, year of birth, race and plant was 2.9 × 10(-4) (p < 0.01). STY ppm-years also displayed a positive exposure-response association with leukemia. STY and BD were strongly correlated, and the separate effects of these two agents could not be estimated. For NHL, a pattern of approximately monotonically increasing rate ratios across deciles of exposure was seen for STY but not for BD; the test of trend was statistically significant in one of five models that used different STY exposure metrics and adjusted for age and other covariates. BD ppm-years and STY ppm-years were not associated with MM. The present analyses indicated a positive exposure-response relationship between BD cumulative exposure and leukemia. This result along with other research and biological information support an interpretation that BD causes leukemia in humans. STY exposure also was positively associated with leukemia, but its independent effect could not be delineated because of its strong correlation with BD, and there is no external support for a STY-leukemia association. STY, but not BD, was associated positively with NHL. The interpretation of this result is uncertain because the exposure-response data were statistically imprecise and because consistent support for causality from other studies is lacking. The current study provides no support for an association between BD or STY and MM.

A comprehensive review of occupational and general population cancer risk: 1,3-Butadiene exposure-response modeling for all leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, myeloid neoplasm and lymphoid neoplasm.

Excess cancer risks associated with 1,3-butadiene (BD) inhalation exposures are calculated using an extensive data set developed by the University of Alabama at Birmingham (UAB) from an epidemiology study of North American workers in the styrene butadiene rubber (SBR) industry. While the UAB study followed SBR workers, risk calculations can be adapted to estimate both occupational and general population risks. The data from the UAB SBR study offer an opportunity to quantitatively evaluate the association between cumulative exposure to BD and different types of cancer, accounting for the number of tasks involving high-intensity exposures to BD as well as confounding associated with the exposures to the multiple other chemicals in the SBR industry. Quantitative associations of BD exposure and cancer, specifically leukemia, can be further characterized by leukemia type, including potential associations with acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myelogenous leukemia (CML), and the groups of lymphoid and myeloid neoplasms. Collectively, these multiple evaluations lead to a comprehensive analysis that makes use of all of the available information and is consistent with the risk assessment goals of the USEPA and other regulatory agencies, and in line with the recommendations of the USEPA Science Advisory Board. While a range of cancer risk values can result from these multiple factors, a preferred case for occupational and general population risk is highlighted. Cox proportional hazards models are used to fit exposure-response models to the most recent UAB data. The slope of the model with cumulative BD ppm-years as the predictor variable is not statistically significantly greater than zero for CML, AML, or, when any one of eight exposure covariates is added to the model, for all leukemias combined. The slope for CLL is statistically significantly different from zero. The slope for myeloid neoplasms is not statistically significantly greater than zero while the slope for lymphoid neoplasms is statistically significantly greater than zero. The excess risk for the general population is largest for lymphoid neoplasms. The best estimates of the environmental concentrations (ECs) associated with an excess risk of 1/100,000 by age 70 years for lymphoid neoplasms, all leukemias, and CLL are EC(1/100,000)'s equal to 0.06, 0.16 and 0.38 ppm, respectively. The best estimates of the occupational BD exposure from 20 to 65 years of age associated with an excess risk of 1/10,000 by age 70 years for lymphoid neoplasms, all leukemias, and CLL are the EC(1/10,000)'s of 2.7, 7.3 and 15.1 ppm, respectively.

High throughput HPLC-ESI(-)-MS/MS methodology for mercapturic acid metabolites of 1,3-butadiene: Biomarkers of exposure and bioactivation.

1,3-Butadiene (BD) is an important industrial and environmental carcinogen present in cigarette smoke, automobile exhaust, and urban air. The major urinary metabolites of BD in humans are 2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene/1-(N-acetyl-L-cystein-S-yl)-2-hydroxybut-3-ene (MHBMA), 4-(N-acetyl-L-cystein-S-yl)-1,2-dihydroxybutane (DHBMA), and 4-(N-acetyl-L-cystein-S-yl)-1,2,3-trihydroxybutyl mercapturic acid (THBMA), which are formed from the electrophilic metabolites of BD, 3,4-epoxy-1-butene (EB), hydroxymethyl vinyl ketone (HMVK), and 3,4-epoxy-1,2-diol (EBD), respectively. In the present work, a sensitive high-throughput HPLC-ESI(-)-MS/MS method was developed for simultaneous quantification of MHBMA and DHBMA in small volumes of human urine (200 µl). The method employs a 96 well Oasis HLB SPE enrichment step, followed by isotope dilution HPLC-ESI(-)-MS/MS analysis on a triple quadrupole mass spectrometer. The validated method was used to quantify MHBMA and DHBMA in urine of workers from a BD monomer and styrene-butadiene rubber production facility (40 controls and 32 occupationally exposed to BD). Urinary THBMA concentrations were also determined in the same samples. The concentrations of all three BD-mercapturic acids and the metabolic ratio (MHBMA/(MHBMA+DHBMA+THBMA)) were significantly higher in the occupationally exposed group as compared to controls and correlated with BD exposure, with each other, and with BD-hemoglobin biomarkers. This improved high throughput methodology for MHBMA and DHBMA will be useful for future epidemiological studies in smokers and occupationally exposed workers.

Cytotoxicity of elastomeric power chains in artificial saliva: an in vitro study.

INTRODUCTION: The main aim of this paper is to investigate the cytotoxicity of elastomeric power chains after stretching and immersion in a solution of artificial saliva. MATERIALS AND METHOD: Two brands of grey polyurethane power chains available from two different firms (GAC, G&H) were selected for cytotoxicity assay. Each segment was stretched up to an initial force of approximately 200 g. Then each segment was kept stretched using appropriate equipment. The samples were tested in artificial saliva at two pH levels, pH7 and pH4. Following incubation, the saliva was removed, filtered and placed in contact with cell culture media using the RD line. RESULTS AND DISCUSSION: At this supernatant dilution, no statistically significant difference was observed between the different groups of power chains studied in terms of cell viability. The GAC and G&H power chains, whether stretched or not and immerged in either pH7 or pH4 saliva, showed no toxic effect on RD cells (human cell line).

Supramolecular elastomer based on polydimethylsiloxanes (SESi) film: synthesis, characterization, biocompatibility, and its application in the context of wound dressing.

Supramolecular elastomer based on polydimethylsiloxanes (SESi) is a kind of novel elastomer cross-linked by the multihydrogen bonds supplied by the functional groups linked to the end of the PDMS chains, such as amide, imidazolidone, pending urea (1,1-dialkyl urea), and bridging urea (1,3-dialkyl urea). SESi showed lower glass transition temperature (T g) at about -113 °C because of the softer chain of PDMS, and could show real rubber-like elastic behaviors and acceptable water vapor transmission rate under room temperature. The high biocompatibility of SESi in the form of films was demonstrated by the cytotoxicity evaluation (MTT cytotoxicity assay and direct contact assay), hemolysis assay, and skin irritation evaluation. Based on detailed comparisons between commercial Tegaderm(™) film and SESi film using a full-thickness rat skin model experiment, it was found that SESi film showed similar wound contraction rate as that of Tegaderm(™) film on day seven, 10, and 14; only on day five, SESi film showed a significant (p < 0.05) lower wound contraction rate. And, the wounds covered with SESi film were filled with new epithelium without any significant adverse reactions, similar with that of Tegaderm(™) film.

Poly(ε-caprolactone)-based copolymers bearing pendant cyclic ketals and reactive acrylates for the fabrication of photocrosslinked elastomers.

Block copolymers of poly(ethylene glycol) and poly(ε-caprolactone) (PCL) with chemically addressable functional groups were synthesized and characterized. Ring-opening polymerization of ε-caprolactone (CL) and 1,4,8-trioxaspiro-[4,6]-9-undecanone (TSU) using α-methoxy, ω-hydroxyl poly(ethylene glycol) as the initiator afforded a copolymer with cyclic ketals being randomly distributed in the hydrophobic PCL block. At an initiator/catalyst molar ratio of 10/1 and a TSU/CL weight ratio of 1/4, a ketal-carrying copolymer (ECT2-CK) with Mn of 52 kDa and a ketal content of 15 mol.% was obtained. Quantitative side-chain deacetalization revealed the reactive ketones without noticeable polymer degradation. In our study, 10 mol.% of cyclic ketals were deprotected and the ketone-containing copolymer was designated as ECT2-CO. Reaction of ECT2-CO with 2-(2-(aminooxy)acetoxy)-ethyl acrylate gave rise to an acrylated product (ECT2-AC) containing an estimated 3-5 acrylate groups per chain. UV-initiated radical polymerization of ECT2-AC in dichloromethane resulted in a crosslinked network (xECT2-AC). Thermal and morphological analyses employing differential scanning calorimetry and atomic force microscopy operated in PeakForce Tapping mode revealed the semicrystalline nature of the network, which contained stiff crystalline lamellae dispersed in a softer amorphous interstitial. Macroscopic and nanoscale mechanical characterizations showed that ECT2-CK exhibited a significantly lower modulus than PCL of a similar molecular weight. Whereas ECT2-CK undergoes a plastic deformation with a distinct yield point and a cold-drawing region, xECT2-AC exhibits a compliant, elastomeric deformation with a Young's modulus of 0.5±0.1 MPa at 37°C. When properly processed, the crosslinked network exhibited shape-memory behaviors, with shape fixity and shape recovery values close to 1 and a shape recovery time of less than 4s at 37°C. In vitro studies showed that xECT2-AC films did not induce any cytotoxic effects on the cultured mesenchymal stem cells. The crosslinkable polyester copolymers can be potentially used as tissue engineering scaffolds and minimally invasive medical devices.

Real-time cellular analysis as a novel approach for in vitro cytotoxicity testing of medical device extracts.

Cytotoxicity measurements are often performed to evaluate the biocompatibility of medical device materials. Here, we describe the use of a real-time cell analyzer (RTCA) system for the investigation of biocompatibility of medical devices by comparing RTCA results to two distinct methods described in the International Organization for Standardization (ISO) guidelines. Mouse L-929 fibroblast proliferation was assessed every 15 min from 24 to 100 h during the pretreatment and postextract addition period. Simultaneously, we performed quantitative cytotoxicity analyses using water-soluble tetrazolium salt (WST-1) and qualitatively scored cytotoxicity by examining changes in morphology at 24-h intervals. The RTCA uses electrical impedance to measure cell viability quantified as a normalized cellular index (CI) which was converted in this study to a reactivity grade. Results from microscopic analyses were expressed as a reactivity grade, based on morphology as defined by the ISO 10993-5:2009. There was a clear correlation between addition of cytotoxic agents and, both, decreased normalized CI and concomitant cell layer destruction observed by microscopy. Results obtained from the colorimetric WST-1 assays also correlated with normalized CI at various time points tested. The results indicate that RTCA allows for automated and accurate assessment of biocompatibility of medical devices and biomaterials.

New approach to the ecotoxicological risk assessment of artificial outdoor sporting grounds.

Artificial surfaces for outdoor sporting grounds may pose environmental and health hazards that are difficult to assess due to their complex chemical composition. Ecotoxicity tests can indicate general hazardous impacts. We conducted growth inhibition (Pseudokirchneriella subcapitata) and acute toxicity tests (Daphnia magna) with leachates obtained from batch tests of granular infill material and column tests of complete sporting ground assemblies. Ethylene propylene diene monomer rubber (EPDM) leachate showed the highest effect on Daphnia magna (EC(50) < 0.4% leachate) and the leachate of scrap tires made of styrene butadiene rubber (SBR) had the highest effect on P. subcapitata (EC(10) = 4.2% leachate; EC(50) = 15.6% leachate). We found no correlations between ecotoxicity potential of leachates and zinc and PAH concentrations. Leachates obtained from column tests revealed lower ecotoxicological potential. Leachates of column tests of complete assemblies may be used for a reliable risk assessment of artificial sporting grounds.

Evaluation of the cytotoxicity of elastomeric ligatures after sterilisation with 0.25% peracetic acid.

INTRODUCTION: Sterilisation using peracetic acid (PAA) has been advocated for orthodontic elastic bands. However, cane-loaded elastomeric ligatures can also become contaminated during processing, packaging, and manipulation before placement in the oral cavity and are therefore susceptible, and possible causes, of cross-contamination. AIM: To test the hypothesis that 0.25% peracetic acid (PAA), following the sterilisation of elastomers, influences the cytotoxicity of elastomeric ligatures on L929 cell lines. MATERIALS AND METHODS: Four hundred and eighty silver elastomeric ligatures were divided into 4 groups of 120 ligatures to produce, Group TP (latex natural, bulk pack, TP Orthodontics), Group M1 (Polyurethane, bulk pack, Morelli), Group M2 (Polyurethane, cane-loaded, Morelli) and Group U (Polyurethane, cane-loaded, Uniden). Of the 120 ligatures in each group, 100 were sterilised in 0.25% PAA at time intervals (N = 20) of 1 hour, 2 hours, 3 hours, 4 hours and 5 hours. The 20 remaining elastomeric ligatures in each group were not sterilised and served as controls. Cytotoxicity was assessed using L929 cell lines and a dye-uptake method. Analysis of variance (ANOVA), followed by the Tukey post hoc test (p < 0.05) determined statistical relevance. RESULTS: There was a significant difference between TP, Morelli and Uniden elastomerics (p < 0.05), but no difference between the two types of Morelli elastomerics at the 1 hour time interval. In addition, there was a significant difference between Group CC and the other groups assessed, except between Groups CC and TP at the 1 hour time interval. The non-sterilised elastomeric ligatures showed similar cell viability to that observed after 1 hour of standard sterilisation. CONCLUSION: PAA did not significantly influence the cytotoxicity of elastomeric ligatures after a sterilisation time of 1 hour and is therefore recommended for clinical use.

Improved biocompatibility of poly (styrene-b-(ethylene-co-butylene)-b-styrene) elastomer by a surface graft polymerization of hyaluronic acid.

Hyaluronic acid (HA) is an important component of extracellular matrix (ECM) in many tissues, providing a hemocompatible and supportive environment for cell growth. In this study, glycidyl methacrylate-hyaluronic acid (GMHA) was first synthesized and verified by proton nuclear magnetic resonance ((1)H NMR) spectroscopy. GMHA was then grafted to the surface of biomedical elastomer poly (styrene-b-(ethylene-co-butylene)-b-styrene) (SEBS) via an UV-initiated polymerization, monitored by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS). The further improvement of biocompatibility of the GMHA-modified SEBS films was assessed by platelet adhesion experiments and in vitro response of murine osteoblastic cell line MC-3T3-E1 with the virgin SEBS surface as the reference. It showed that the surface modification with HA strongly resisted platelet adhesion whereas improved cell-substrate interactions.

A drug-in-adhesive matrix based on thermoplastic elastomer: evaluation of percutaneous absorption, adhesion, and skin irritation.

A novel drug-in-adhesive matrix was designed and prepared. A thermoplastic elastomer, styrene-isoprene-styrene (SIS) block copolymer, in combination with tackifying resin and plasticizer, was employed to compose the matrix. Capsaicin was selected as the model drug. The drug percutaneous absorption, adhesion properties, and skin irritation were investigated. The results suggested that the diffusion through SIS matrix was the rate-limiting step of capsaicin percutaneous absorption. [SI] content in SIS and SIS proportions put important effects on drug penetration and adhesion properties. The chemical enhancers had strong interactions with the matrix and gave small effect on enhancement of drug skin permeation. The in vivo absorption of samples showed low drug plasma peaks and a steady and constant plasma level for a long period. These results suggested that the possible side effects of drug were attenuated, and the pharmacological effects were enhanced with an extended therapeutic period after application of SIS matrix. The significant differences in pharmacokinetic parameters produced by different formulations demonstrated the influences of SIS copolymer on drug penetrability. Furthermore, the result of skin toxicity test showed that no skin irritation occurred in guinea pig skin after transdermal administration of formulations.

Human health risk assessment of synthetic turf fields based upon investigation of five fields in Connecticut.

Questions have been raised regarding possible exposures when playing sports on synthetic turf fields cushioned with crumb rubber. Rubber is a complex mixture with some components possessing toxic and carcinogenic properties. Exposure is possible via inhalation, given that chemicals emitted from rubber might end up in the breathing zone of players and these players have high ventilation rates. Previous studies provide useful data but are limited with respect to the variety of fields and scenarios evaluated. The State of Connecticut investigated emissions associated with four outdoor and one indoor synthetic turf field under summer conditions. On-field and background locations were sampled using a variety of stationary and personal samplers. More than 20 chemicals of potential concern (COPC) were found to be above background and possibly field-related on both indoor and outdoor fields. These COPC were entered into separate risk assessments (1) for outdoor and indoor fields and (2) for children and adults. Exposure concentrations were prorated for time spent away from the fields and inhalation rates were adjusted for play activity and for children's greater ventilation than adults. Cancer and noncancer risk levels were at or below de minimis levels of concern. The scenario with the highest exposure was children playing on the indoor field. The acute hazard index (HI) for this scenario approached unity, suggesting a potential concern, although there was great uncertainty with this estimate. The main contributor was benzothiazole, a rubber-related semivolatile organic chemical (SVOC) that was 14-fold higher indoors than outdoors. Based upon these findings, outdoor and indoor synthetic turf fields are not associated with elevated adverse health risks. However, it would be prudent for building operators to provide adequate ventilation to prevent a buildup of rubber-related volatile organic chemicals (VOC) and SVOC at indoor fields. The current results are generally consistent with the findings from studies conducted by New York City, New York State, the U.S. Environmental Protection Agency (EPA), and Norway, which tested different kinds of fields and under a variety of weather conditions.

Synthetic turf field investigation in Connecticut.

The primary purpose of this study was to characterize the concentrations of volatile organic compounds (VOC), semivolatile organic compounds (SVOC), rubber-related chemicals such as benzothiazole (BZT) and nitrosamine, and particulate matter (PM(10)) in air at synthetic turf crumb rubber fields. Both new and older fields were evaluated under conditions of active use. Three types of fields were targeted: four outdoor crumb rubber fields, one indoor facility with crumb rubber turf, and an outdoor natural grass field. Background samples were collected at each field on grass. Personal air sampling was conducted for VOC, BZT, nitrosamines, and other chemicals. Stationary air samples were collected at different heights to assess the vertical profile of release. Air monitoring for PM(10) was conducted at one height. Bulk samples of turf grass and crumb rubber were analyzed, and meteorological data were recorded. Results showed that personal concentrations were higher than stationary concentrations and were higher on turf than in background samples for certain VOC. In some cases, personal VOC concentrations from natural grass fields were as high as those on turf. Naphthalene, BZT, and butylated hydroxytoluene (BHT) were detected in greater concentration at the indoor field compared to the outdoor fields. Nitrosamine air levels were below reporting levels. PM(10) air concentrations were not different between on-field and upwind locations. All bulk lead (Pb) samples were below the public health target of 400 ppm. More research is needed to better understand air quality at indoor facilities. These field investigation data were incorporated into a separate human health risk assessment.

Fabrication and characterization of elastomeric polyester/carbon nanotubes nanocomposites for biomedical application.

A novel biodegradable polymer elastomer nanocomposite composing of poly(1,8-octanediol-citrate) (POC) polymer matrix and carbon nanotubes (CNTs) additive was successfully fabricated and systematically investigated using Fourier transform infrared (FT-IR), X-ray diffractometer (XRD), differential scanning calorimetry (DSC), tensile test, incubation and cytotoxicity tests. It was found that the addition of CNTs in POC elastomer did not result in any noticeable change in its chemical structure and the amorphous state. However, the tensile strength and elongation at break were greatly improved by the addition of CNTs in POC polymer matrix. It revealed that the swelling ratio and percentage of weight loss of POC/CNTs nanocomposite were lower, compared with the pure POC material. Moreover, the adsorption amount of bovine serum albumin (BSA) increased with an increase of the CNTs mass content in POC matrix revealing the enhanced hydrophilicity of POC/CNTs nanocomposites contributed by the carboxyl of the CNTs. Additionally, the cytotoxicity tests with L929 cell line revealed that the experimental POC/CNTs nanocomposites possessed good in vitro biocompatibility.

Cytotoxicity of orthodontic materials assessed by survival tests in Saccharomyces cerevisiae.

The aim of this study was to assess the cytotoxicity of orthodontic materials (brackets, wires, resin, elastomers and silver solder) using Saccharomyces cerevisiae as a model organism. The induction of cytotoxicity was assessed by two different tests using the wild-type S. cerevisiae strain FF18733: (1) direct exposure to orthodontic materials in YPD broth, and (2) exposure to artificial commercial saliva pre-treated with orthodontic materials. Only the silver solder was tested in mutant S. cerevisiae strains to investigate the origin of the observed cytotoxicity. Colony forming units per mL counts were carried out in all experiments and compared to controls to detect significant survival differences. The results showed that only the silver solder induced significant cytotoxicity, which might have occurred via oxidative stress, although this mechanism is not completely understood. Moreover, S. cerevisiae proved to be a reliable and useful model microorganism for evaluating the cytotoxicity of clinical materials.

1,3-Butadiene: I. Review of metabolism and the implications to human health risk assessment.

1,3-Butadiene (BD) is a multisite carcinogen in laboratory rodents following lifetime exposure, with mice demonstrating greater sensitivity than rats. In epidemiology studies of men in the styrene-butadiene rubber industry, leukemia mortality is associated with butadiene exposure, and this association is most pronounced for high-intensity BD exposures. Metabolism is an important determinant of BD carcinogenicity. BD is metabolized to several electrophilic intermediates, including epoxybutene (EB), diepoxybutane (DEB), and epoxybutane diol (EBD), which differ considerably in their genotoxic potency (DEB >> EB > EBD). Important species differences exist with respect to the formation of reactive metabolites and their subsequent detoxification, which underlie observed species differences in sensitivity to the carcinogenic effects of BD. The modes of action for human leukemia and for the observed solid tumors in rodents are both likely related to the genotoxic potencies for one or more of these metabolites. A number of factors related to metabolism can also contribute to nonlinearity in the dose-response relationship, including enzyme induction and inhibition, depletion of tissue glutathione, and saturation of oxidative metabolism. A quantitative risk assessment of BD needs to reflect these species differences and sources of nonlinearity if it is to reflect the current understanding of the disposition of BD.

Biodegradable elastomeric networks: highly efficient cross-linking of poly(trimethylene carbonate) by gamma irradiation in the presence of pentaerythritol triacrylate.

Biodegradable elastomeric poly(trimethylene carbonate) (PTMC) networks were efficiently formed by gamma irradiating the linear polymer in the presence of pentaerythritol triacrylate (PETA). The properties of networks formed upon irradiation of PTMC films containing (0, 1, 5 wt %) PETA as a cross-linking aid were evaluated. The gel contents and network densities increased with increasing PETA contents, irradiation dose, and initial polymer molecular weights. At a dose of 25 kGy, networks with gel fractions up to 0.96 could be obtained. The networks were noncytotoxic, had elastic moduli below 10.7 MPa and high tensile strengths of up to 37.7 MPa. The incorporation of PETA also improved the resistance to creep and to tear propagation significantly, resulting in permanent set values that were as low as 0.9% strain and tear strengths up to 9.3 ± 2.0 N/mm. Furthermore, the enzymatic erosion rates of the networks could be decreased from 12.0 ± 2.9 to 3.0 ± 1.6 µm/day. These biodegradable elastomeric PTMC networks may be utilized in a broad range of medical applications.