The EPC Approach to Estimating Safety from Exposure to Environmental Chemicals

Reference doses (RfDs) and reference concentrations (RfCs) developed by the United States Environmental Protection Agency (USEPA) are typically used in the quantitation of risk of potential adverse human health effects from exposure to environmental chemicals. For a large number of chemicals, however, USEPA RfDs and RfCs have not yet been determined. Thus, for risk assessments that involve a large number of chemicals, there is insufficient toxicity information with which to evaluate potential adverse human health effects for all chemicals present at a particular site. Due to this insufficiency, the risk assessor must either (1) ignore potential exposures on the assumption that omitting these exposures does not significantly alter decisions concerning the remediation of the site or (2) undertake a lengthy and costly analysis to generate the necessary RfDs or RfCs. A potential solution to this problem is to develop estimated permissible concentrations (EPCs), values which represent permissible environmental concentrations or related acceptable daily dosages derived from occupational exposure limits. In the present analysis, acceptable daily dosages determined using the EPC method were compared to USEPA RfDs or RfCs which were converted to dosages based on standard exposure assumptions. Based on a comparative analysis of EPCs and USEPA reference values for 103 chemicals, it was found that EPC daily dosages represent a reasonably conservative surrogate value when USEPA or state reference values are unavailable. Given that there are hundreds of chemicals with occupational exposure limits but no state or USEPA reference values, acceptance of the EPC methodology would provide an interim solution for the problem of insufficient toxicity information for a substantial number of environmental chemical contaminants.     

Effects of subsidising bus travel on the occurrence of road traffic casualties.

Between 1975 and 1 April 1986, public transport by bus in the metropolitan county of South Yorkshire, England, was increasingly subsidised. Trends in road traffic accident casualties between 1974 and 1983 in all the six provincial English metropolitan counties have been compared in order to examine the possible effect of this unique subsidy on the incidence of road traffic accident casualties. During that period the total number of casualties in South Yorkshire did not change significantly compared to the other metropolitan counties. However, the proportion of all casualties in South Yorkshire who were bus occupants did increase relative to other metropolitan counties, indicating either an increase in the amount of bus travel or a decrease in travel by other modes. There was a large increase in bus patronage in South Yorkshire relative to the other metropolitan counties, and the conclusion is that it is the transport policy in South Yorkshire which resulted in an actual increase in distances travelled by bus. Since bus is the safest form of road travel, it is concluded that the public transport subsidy in South Yorkshire has benefited the health of the local population by providing the social amenity of additional travel at the least additional health cost.     

Effects of a monoclonal antibody raised against nerve growth factor on skeletal pain and bone healing after fracture of the C57BL/6J mouse femur.

A closed femur fracture pain model was developed in the C57BL/6J mouse. One day after fracture, a monoclonal antibody raised against nerve growth factor (anti-NGF) was delivered intraperitoneally and resulted in a reduction in fracture pain-related behaviors of approximately 50%. Anti-NGF therapy did not interfere with bone healing as assessed by mechanical testing and histomorphometric analysis. INTRODUCTION: Current therapies to treat skeletal fracture pain are limited. This is because of the side effect profile of available analgesics and the scarcity of animal models that can be used to understand the mechanisms that drive this pain. Whereas previous studies have shown that mineralized bone, marrow, and periosteum are innervated by sensory and sympathetic fibers, it is not understood how skeletal pain is generated and maintained even in common conditions such as osteoarthritis, low back pain, or fracture. MATERIALS AND METHODS: In this study, we characterized the pain-related behaviors after a closed femur fracture in the C57BL/6J mouse. Additionally, we assessed the effect of a monoclonal antibody that binds to and sequesters nerve growth factor (anti-NGF) on pain-related behaviors and bone healing (mechanical properties and histomorphometric analysis) after fracture. RESULTS: Administration of anti-NGF therapy (10 mg/kg, days 1, 6, and 11 after fracture) resulted in a reduction of fracture pain-related behaviors of approximately 50%. Attenuation of fracture pain was evident as early as 24 h after the initial dosing and remained efficacious throughout the course of fracture pain. Anti-NGF therapy did not modify biomechanical properties of the femur or histomorphometric indices of bone healing. CONCLUSIONS: These findings suggest that therapies that target NGF or its cognate receptor(s) may be effective in attenuating nonmalignant fracture pain without interfering with bone healing.     

Comparison between two valsalva techniques for improvement of hypopharyngeal nasendoscopy: a preliminary communication

Objective: To compare the nasal valsalva with the trumpet manoeuvre and anterior neck skin traction as aids to nasendoscopic examination of the hypopharynx. Design: Randomised, controlled comparison of examination techniques. Setting: Single tertiary referral centre. Participants: Twenty‐six adult patients requiring hypopharyngeal nasendoscopic examination were recruited. Patients were examined with both techniques in a randomised order that was recorded to video cassette. Main Outcome Measures: Blinded assessment of the percentage visualisation of the pyriform fossae, post‐cricoid and upper oesophageal sphincter was carried out by three consultant otolaryngologists independently. Results: Mean percentage scores (and 95% confidence intervals) for nasal valsalva versus trumpet manoeuvre for the three consultants, respectively, were as follows: right pyriform fossa: 77(68, 87) versus 80(71, 91), 61(55, 66) versus 60(54, 66), 46(38, 54) versus 45(37, 54); left pyriform fossa: 76(65, 87) versus 80(69, 91), 59(53, 64) versus 55(49, 61), 42(35, 49) versus 42(35, 50); post‐cricoid: 55(44, 67) versus 59(47, 71), 53(46, 60) versus 53(46, 60), 32(25, 39) versus 32(25, 39); upper oesophageal sphincter: 11(1, 21) versus 21(11, 31), 15(9, 21) versus 20(14, 26), 4(0, 8) versus 7(3, 11). No significant difference was found between the two techniques at any subsite. Individual differences were noted in a minority of patients where one or other technique gave a clearly improved view. Conclusions: The nasal valsalva and the trumpet manoeuvre with anterior neck skin traction are complementary techniques for improving the view of the hypopharynx.