Health assessment of phosgene: approaches for derivation of reference concentration.

This paper describes the derivation of the chronic reference concentration (RfC) for human inhalation of phosgene that was recently added to the Environmental Protection Agency's (EPA) Integrated Risk Information System (IRIS) data base (U.S. EPA, 2005. Toxicological Review of Phosgene: In Support of Summary Information on the Integrated Risk Information System (IRIS). Available online at: ). The RfC is an estimate of daily phosgene exposure to the human population that is likely to be without appreciable risk of deleterious effects during a lifetime. [For this and other definitions relevant to EPA risk assessments refer to the glossary of terms in the US EPA IRIS website (http://www.epa.gov/IRIS).] Phosgene is a potential environmental pollutant that is primarily used as a catalyst in the polyurethane industry. It is a gas at room temperature, and in aqueous solution it rapidly hydrolyzes to CO2 and HCl. In the absence of chronic human health effects information and lifetime animal cancer bioassays, the RfC is based on two 12-week inhalation studies in F344 rats which measured immune response and pulmonary effects, respectively. The immune response study showed impaired clearance of bacteria that was administered into the lungs of rats immediately after exposure to phosgene at concentrations of 0.1, 0.2 and 0.5 ppm. It also showed that the immune response in uninfected rats was stimulated by phosgene exposure at all concentrations. The pulmonary effects study showed a progressive concentration-related thickening and inflammation in the bronchiolar regions of the lung that was mild at 0.1 ppm and severe at 1.0 ppm. An increase in collagen content, as observed with histological collagen stains, was observed at 0.2 ppm and above. Though there is considerable uncertainty associated with the species and exposure duration employed, this endpoint is considered an indication of chronic lung injury of potential relevance to humans. Three different approaches for RfC derivation were taken in analyzing these studies: (1) the traditional NOAEL/LOAEL method; (2) the benchmark dose (BMD); and (3) the categorical regression for the analysis of severity-graded pulmonary damage data using the recently revised USEPA CatReg software. The BMD approach was selected as the method of choice to determine the RfC for phosgene because it has several advantages compared to the NOAEL/LOAEL: (1) it is not restricted to the set of doses used in the experiments; (2) the result is not dependent on sample size; (3) it incorporates information on statistical uncertainty. The CatReg approach allowed the incorporation of data on the severity of the pathological lesions, and therefore it complemented the other approaches. The BMD approach could not be applied to the immune response data because it was not possible to define an adverse effect level for bacterial resistance. However, NOAEL/LOAEL values for immune responses were consistent with benchmark dose levels derived from lung pathology data and used in the derivation of the RfC. The preferred RfC method and derivation involved dividing the benchmark dose from the collagen staining data (0.03 mg/m3) by a composite uncertainty factor of 100: RfC=0.03/100=3E-4 mg/m3.

Rare case of recurrent angiokeratoma of Fordyce on penile shaft.

Angiokeratomas are benign cutaneous vascular lesions characterized by dilated thin-walled blood vessels lying in the upper part of the dermis, mostly associated with an epidermal reaction such as acanthosis and/or hyperkeratosis. Angiokeratomas of Fordyce are predominantly located on the scrotum and are only rarely found on the penis and then usually on the glans penis. We report a rare case of angiokeratoma of Fordyce located on the shaft of the penis and associated with two recurrences after appropriate surgical excision.

Early recurrence of primary focal segmental glomerulosclerosis in an older cadaveric renal allograft recipient resistant to plasmapheresis.

We report an unusual case of recurrent primary focal segmental glomerulosclerosis in an apparent low-risk cadaveric renal allograft recipient only 2 days after transplantation, who did not respond to repeated courses of plasmapheresis.

Can the outcome of older donor kidneys in transplantation be predicted? An analysis of existing scoring systems.

The use of older cadaveric donors in kidney transplantation is increasing. The transplant outcome of the single older kidney is generally inferior prompting some to recommend dual kidney transplantation. The ability to predict the outcome of the solitary marginal kidney becomes clinically important. Such insight might allow for better allocation strategies that would minimize poorer outcomes while permitting optimal rationalization of this scarce resource. A retrospective, single center review of 79 single kidney transplants from 50 donors aged > or =55 yr was performed. We tested the validity of published scoring strategies to predict subsequent recipient kidney function. Receiver operating characteristic curve analysis was used to quantify the donor strategies separating good and poor outcomes based upon recipient creatinine clearance (CrCl) <30 mL/min. Two pre-transplant donor assessment strategies, Nyberg score and donor CrCl (dCrCl) were found to predict subsequent kidney function in recipients. When Nyberg variables (cold ischemia time, donor diabetes and hypertension status, incremental donor age >55 yr and cause of death) in conjunction with the dCrCl were considered, they were no better than dCrCl alone. Although dCrCl had a reasonable negative predictive ability, the positive predictive value was <50%. Our analysis suggests that a dCrCl of > or =70 mL/min is a better discriminator of subsequent kidney function outcomes than a dCrCl of 90 mL/min as recommended by the Dual Transplant Registry.