Application of the Draft NIOSH Occupational Exposure Banding Process to Bisphenol A: A case study

Bisphenol A is a commercially important chemical used to make polycarbonate plastic, epoxy resins, and other specialty products. Despite an extensive body of in vitro, animal and human observational studies on the effects of exposure to bisphenol A, no authoritative bodies in the U.S. have adopted or recommended occupational exposure limits for bisphenol A. In 2017, the National Institute for Occupational Safety and Health published a Draft process for assigning health-protective occupational exposure bands, i.e., an airborne concentration range, to chemicals lacking an occupational exposure limit. Occupational exposure banding is a systematic process that uses both quantitative and qualitative toxicity information on selected health effect endpoints to assign an occupational exposure band for a chemical. The Draft process proposes three methodological tiers of increasing complexity for assigning an occupational exposure band. We applied Tier 1 (based on the Globally Harmonized System of Classification and Labelling) and Tier 2 (based on authoritative sources/reviews) to assign an occupational exposure band to bisphenol A. Under both Tier 1 and 2, the occupational exposure band for bisphenol A was “E” (<0.01?mg/m³), an assignment based on eye damage. “E” is the lowest exposure concentration range, reserved for chemicals with high potential toxicity. If eye damage was excluded in assigning an air concentration exposure range, then bisphenol A would band as “D” (>0.01 to 0.1?mg/m³) under Tier 1 (based on reproductive toxicity and respiratory/skin sensitization) and under Tier 2 (based on specific target organ toxicity-repeated exposure). In summary, Tiers 1 and 2 gave the same occupational exposure band for bisphenol A when eye damage was included (“E”) or excluded (“D”) as an endpoint.     

Shear bond strengths of prosthodontic adhesive systems to a nickel-chromium-beryllium alloy.

Panavia, a composite resin luting agent containing phosphate monomers, bonds chemically to air-abraded base metal alloys and is particularly suited for cementing resin-bonded retainers. Another adhesive methodology (Silicoater system) incorporates a pyrolytically applied silica layer to metal substrates to promote bonding of a resin adhesive. The object of this study was to compare prosthodontic adhesive systems that incorporated the Silicoater system and/or Panavia. The results showed that the surface treatment that provided significantly higher shear bond strengths was the Silicoater system and a layer of unfilled resin. A second test evaluated use of Panavia as a metal opaquing material beneath laboratory light-curing resins. Results showed that Panavia Opaque material was displaced peripherally during placement of overlying laboratory composite resin veneers. This resulted in an uneven intermediate layer of Panavia.     

Counter incision is a safe and effective method for alternative reservoir placement during inflatable penile prosthesis surgery

BackgroundAlternative reservoir placement is increasingly popular during inflatable penile prosthesis (IPP) surgery to prevent intraperitoneal positioning, bowel, bladder, or vascular injury in patients with prior pelvic surgeries. Counter incision (CI) can be used for submuscular reservoir placement in high risk patients, however series exploring the safety remain limited.MethodsA database of IPP surgeries was queried for use of a CI during reservoir placement to compare 90-day clinical outcomes in a retrospective case-control study. Primary outcome was device infections, with secondary outcomes including reservoir herniation, hematoma, device malfunction rates, and operative times. Groups were compared using Kruskal-Wallis and Chi-Squared tests, with multivariate logistic regression models to identify predictors of infectious complications.ResultsA total of 534 cases met criteria, of which 51 (9.6%) used a CI for reservoir placement. The CI cohort included significantly more removal and replacements, 45.1% vs. 20.9% (P<0.001). Thirty-one CI patients (61.0%) had undergone prior prostatectomy compared to 134 (27.7%) non-CI patients (P=0.001). The most common reasons for CI were prior prostatectomy and inguinal hernia repair. Median operative time was 17 minutes longer in the CI group (74 vs. 57 minutes, P<0.001). Device infection rates were similar (2.0% vs. 4.1%, P=0.71), as were rates of hematoma (5.9% vs. 2.7%, P=0.19), and device malfunction (0.0% vs. 1.4% P=1.00).ConclusionsComplication rates were similar between CI and non-CI cohorts, even in a subset where approximately half the cases were removal and replacements. For physicians not comfortable with alternative placement through a penoscrotal or infrapubic incision, this offers a reasonable alternative and permits use of three-piece devices in patients with a hostile pelvis.     

Thrombomodulin expression by human keratinocytes. Induction of cofactor activity during epidermal differentiation.

Thrombomodulin is an endothelial cell surface glycoprotein that inhibits the procoagulant activities of thrombin and accelerates activation of the anticoagulant protein C. Because protein C deficiency is associated with cutaneous thrombosis, we investigated the expression of thrombomodulin in human skin. Thrombomodulin was detected by immunohistochemical staining both in dermal endothelial cells and in epidermal keratinocytes. Within the epidermis, thrombomodulin staining was limited to keratinocytes of the spinous layer, suggesting that thrombomodulin is induced when basal keratinocytes begin to terminally differentiate. Thrombomodulin expression also correlated with squamous differentiation in epidermal malignancies; little or no thrombomodulin staining was seen in five basal cell carcinomas, whereas strong thrombomodulin staining was observed in each of five squamous cell carcinomas. Human foreskin keratinocytes cultured in medium containing 0.07 mM calcium chloride synthesized functional thrombomodulin with cofactor activity comparable to thrombomodulin in human umbilical vein endothelial cells. Stimulation of keratinocyte differentiation with 1.4 mM calcium chloride for 48 h produced 3.5-, 3.2-, and 5.6-fold increases in thrombomodulin cofactor activity, antigen, and mRNA, respectively. These observations suggest that thrombin is regulated by keratinocyte thrombomodulin at sites of cutaneous injury, and indicate a potential role for thrombomodulin in epidermal differentiation.     

Hyperhomocysteinemia, endothelial dysfunction, and cardiovascular risk: the potential role of ADMA

Hyperhomocysteinemia is an emerging risk factor for cardiovascular disease and stroke. The mechanisms underlying the pathophysiology of hyperhomocysteinemia are not completely defined, but endothelial dysfunction resulting from impaired bioavailability of nitric oxide is a consistent finding in experimental models. One potential mechanism for decreased nitric oxide bioavailability is inhibition of endothelial nitric oxide synthase by its endogenous inhibitor, asymmetric dimethylarginine (ADMA). Elevated plasma levels of ADMA have been found in association with hyperhomocysteinemia and endothelial dysfunction in both animals and humans. Additional studies are required to determine the mechanisms by which ADMA accumulates in hyperhomocysteinemia and to define the importance of ADMA in the endothelial dysfunction of hyperhomocysteinemia in vivo.     

In Vitro Activity of wALADin Benzimidazoles against Different Life Cycle Stages of Plasmodium Parasites

wALADin1 benzimidazoles are specific inhibitors of δ-aminolevulinic acid dehydratase from Wolbachia endobacteria of filarial nematodes. We report that wALADin1 and two derivatives killed blood stage Plasmodium falciparum in vitro (50% inhibitory concentrations, 39, 7.7, and 12.8 μM, respectively). One of these derivatives inhibited gliding motility of Plasmodium berghei ANKA infectious sporozoites with nanomolar affinity and blocked invasion into hepatocytes but did not affect intrahepatocytic replication. Hence, wALADin1 benzimidazoles are tools to study gliding motility and potential antiplasmodial drug candidates.     

Glutathione peroxidase-1 plays a major role in protecting against angiotensin II-induced vascular dysfunction

Levels of reactive oxygen species, including hydrogen peroxide(,) increase in blood vessels during hypertension and in response to angiotensin II (Ang II). Although glutathione peroxidases are known to metabolize hydrogen peroxide, the role of glutathione peroxidase during hypertension is poorly defined. We tested the hypothesis that glutathione peroxidase-1 protects against Ang II-induced endothelial dysfunction. Responses of carotid arteries from Gpx1-deficient (Gpx1(+/-) and Gpx1(-/-)) and Gpx1 transgenic mice, and their respective littermate controls, were examined in vitro after overnight incubation with either vehicle or Ang II. Under control conditions, relaxation to acetylcholine (ACh; an endothelium-dependent agonist) was similar in control, Gpx1(+/-), and Gpx1 transgenic mice, whereas in Gpx1(-/-) mice, responses to ACh were impaired. In control mice, ACh-induced vasorelaxation was not affected by 1 nmol/L of Ang II. In contrast, relaxation to ACh in arteries from Gpx1(+/-) mice was inhibited by approximately 60% after treatment with 1 nmol/L of Ang II, indicating that Gpx1 haploinsufficiency markedly enhances Ang II-induced endothelial dysfunction. A higher concentration of Ang II (10 nmol/L) selectively impaired relaxation to ACh in arteries from control mice, and this effect was prevented in arteries from Gpx1 transgenic mice or in arteries from control mice treated with polyethylene glycol-catalase (which degrades hydrogen peroxide). Thus, genetic and pharmacological evidence suggests a major role for glutathione peroxidase-1 and hydrogen peroxide in Ang II-induced effects on vascular function.     

Workplace Monitoring of Occupational Exposure to Refractory Ceramic Fiber—A 17-Year Retrospective

This article presents a 17-year (1990–2006) retrospective summary of ongoing studies of occupational exposure to refractory ceramic fiber (RCF) in the United States. Beginning in 1990, RCF producers integrated and harmonized individual workplace monitoring programs to provide data useful for various longitudinal and cross-sectional analyses, benchmarking, and various technical analyses. For 10 of these 17 years, the program has been conducted in partnership with government agencies, first a 5-year (1993–1998) program with the U.S. Environmental Protection Agency and later another 5-year (2002–2006) program with the Occupational Safety and Health Administration and the National Institute for Occupational Safety and Health. This article updates earlier published studies and provides lessons to be learned in the design of industrial hygiene monitoring and control programs.