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Biomedical subjects

D M Proctor

Publications and source records attributed to D M Proctor.

10 recordsLinked to original sources

An environmental hazard assessment of low-level dermal exposure to hexavalent chromium in solution among chromium-sensitized volunteers.

To evaluate the potential for elicitation of allergic contact dermatitis from contact with standing water in the environment, 26 persons known to be allergic to hexavalent chromium [Cr(VI)] were exposed to 25 to 29 mg/L Cr(VI) by immersion of one arm for 30 minutes per day on 3 consecutive days in a potassium dichromate bath. Sixteen of the 26 volunteers demonstrated either no or an equivocal response to the Cr(VI) challenge. Ten of the volunteers developed a few papules or vesicles (1 to approximately 15), mild redness, and pruritus on the Cr(VI)-challenged arm. Histopathological examination of the papules revealed spongiosis and perieccrine and perivascular inflammation. The responses were diagnosed as acute perieccrine reactions. It was concluded that exposure to similar concentrations of Cr(VI) in the environment does not pose an allergic contact dermatitis hazard, even to Cr-sensitized persons.

Biopsy↗

The prevalence of chromium allergy in the United States and its implications for setting soil cleanup: a cost-effectiveness case study.

Hexavalent chromium [Cr(VI)] elicits allergic contact dermatitis (ACD) among previously sensitized individuals, and some regulatory agencies have suggested the need for Cr(VI) soil standards that are protective of this health end point. To assess the cost effectiveness of implementing ACD-based standards, it is necessary to understand the prevalence of Cr(VI) sensitivity in the general population. More than 30 published studies from 1950 to 1997 were reviewed to determine the prevalence of Cr(VI) sensitivity. No random survey of the general United States (U.S.) population has been performed to date, but the prevalence of Cr(VI) sensitization among North American clinical cohorts (e.g., patients of dermatological clinics) was reported to be 1% in 1996. The prevalence of Cr(VI) sensitivity among the general U.S. population is estimated to be 0.08%. This estimate was calculated by dividing the current U.S. clinical prevalence estimate (1%) by the ratio of Cr(VI) sensitization in clinical vs general populations in The Netherlands (12). A retrospective cost/benefit analysis for sites in Jersey City, New Jersey, suggests that remediation of soils to protect against elicitation of ACD in sensitized individuals is not a cost-effective use of public health resources.

Carcinogens, Environmental↗

Preliminary assessment of PCB risks to human and ecological health in the lower Passaic River.

Concentrations of Aroclor mixtures and specific polychlorinated biphenyl (PCB) congeners were measured in surface sediments and aquatic biota (striped bass fillet, mummichog, and blue crab muscle and hepatopancreas) collected from the lower Passaic River. Several of the 47 surface sediment samples contained Aroclor concentrations that exceeded a National Oceanic and Atmospheric Administration (NOAA) benchmark level for "total PCBs" (22.7 micrograms/kg). Each of the 18 PCB congeners analyzed in aquatic biota was detected in one or more tissue samples, and numerous congeners were detected in every sample (IUPAC numbers 77, 105, 114, 118, 123, 126, 156, 157, 167, and 189). PCB congener concentrations were similar to those that have been reported in fish from other waterways that contain elevated levels of PCBs. Congener 118 was present at the highest concentration in almost all samples, and constituted 14-60% of the total PCB mass (sum of all congener masses) measured in any given tissue sample. In spite of the prevalence of PCB congeners in biota tissues (up to 1314 micrograms/kg total PCBs), Aroclors were not detected in bass or crab samples at a limit of detection of 33-55 micrograms/kg. This anomaly may be due to selective degradation of certain PCB congeners that are used to analytically recognize and quantitate Aroclors. Using the measured sediment concentrations, a food web model accurately predicted blue crab muscle concentrations of individual PCB congeners (typically within a factor of two) and was also fairly accurate for mummichog (typically within an order of magnitude). Concentrations in striped bass fillet were underestimated by factors of approximately 20-140. Increased cancer risk estimates associated with fish and crab consumption were obtained using four different methods. Using Aroclor tissue concentrations (one-half the limit of detection) and an Aroclor slope factor, total risks were 2.6 x 10(-6); using the "total PCB" measurements and an Aroclor slope factor, total risks were 1.9 x 10(-5); the "PCB-TEQ" method yielded total risks of 6.5 x 10(-4); and USEPA's recent suggested approach for evaluating "dioxin-like" and non-"dioxin-like" effects resulted in a total risk of 6.6 x 10(-4). This wide range in risk estimates indicates that it is critical to the risk management decision-making process that data requirements and risk assessment objectives be carefully evaluated early in the investigation process.

Animals↗

Urinary chromium as a biological marker of environmental exposure: what are the limitations?

Public concern has mounted recently about environmental exposures to chromium in soil, tap water, and ambient air. In response, agencies charged with protecting public health have attempted to study exposure by monitoring urinary chromium levels among potentially exposed populations. While urinary biomonitoring of occupationally exposed workers has been successfully used to assess high-level inhalation exposures in the workplace, evaluating low-level environmental exposures has been problematic. Due to these problems, before an extensive biological monitoring study is conducted of those exposed to low levels of environmental chromium, several issues must be resolved. First, exposures to chromium must occur at the same time as sampling, because the biological half-life of chromium in urine is very short (less than 2 days). Second, reduced bioavailability and bioaccessibility via the oral and dermal routes of exposure limit the capacity of urinary monitoring to measure environmental exposures (e.g., systemic dose is too small to be measured). Third, the dose of chromium must be sufficient such that it may be reliably measured above background levels in urine (range of 0.2 to 2 microg/liter) and above the analytical limit of detection (0.2 microg/liter). Fourth, the inter- and intrapersonal variability in background levels of urinary chromium is known to be significant and influenced by food and beverage intake, smoking, and exercise. Thus, the role of each factor must be carefully understood. Finally, it is imperative to have developed a complete understanding of the clinical significance of elevated urinary chromium levels before a study is performed, because higher than background levels, in and of themselves, are not indicative of a significant health concern. The route of exposure, valence of chromium to which people were exposed, exposure time, and duration must all be understood before the biological data can be implemented. We have conducted a total of nine human exposure studies over the past 3 years in an attempt to understand the kinetics of chromium and the impact on urinary, red blood cell (RBC), and plasma biomonitoring programs. The results of these studies are described here and our recommendations are offered for how to design and implement a urinary chromium biomonitoring study. In our view, given some evidence that the dose of hexavalent chromium [Cr(VI)] is sufficient to be measurable above background concentrations of total chromium [Cr(III) and Cr(VI)], duplicated measurements of chromium in plasma and RBCs are, in most cases, a more definitive gauge of environmental exposure than urinary biomonitoring.

Biological Availability↗

Estimation of a chromium inhalation reference concentration using the benchmark dose method: a case study.

The benchmark dose (BD) method has been proposed as an alternative to the NOAEL/UF method for setting reference levels. The BD is the 95% lower confidence limit on a dose corresponding to a 10% increase (or relative change) in an adverse effect. A case study exploring the suitability of the current Cr(III) and Cr(VI) inhalation toxicity data bases to the BD approach is presented. Because chromic acid mists, typical of many occupational Cr(VI) exposures, present a toxicological profile different from that of Cr(VI) particulates, representative of environmental exposures, Cr(VI) particulate data were evaluated separately from Cr(VI) acidic mist data. The current Cr(III) and Cr(VI) acidic mist data bases proved inadequate for BD analysis due to data and/or study quality limitations. Benchmark reference concentrations (RfCs) for particulate Cr(VI) ranging from 0.34 microgram/m3 (for lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF)) to 1.4 micrograms/m3 (for increased lung weights) are derived from data taken from U. Glaser et al. (Arch. Toxicol. 57, 250-256, 1985) and U. Glaser et al. (Environmental Hygiene II, Springer-Verlag, Berlin/New York, 1990). A Cr(VI) particulate RfC of 0.34 microgram/m3 based upon LDH in BALF as the critical effect is proposed. This value may be viewed as conservative since it represents the 95% lower confidence limit on the dose associated with a 10% increase in response for a sensitive endpoint and has appropriate dosimetric adjustments and uncertainty factors incorporated.

Administration, Inhalation↗

An alternative to the USEPA's proposed inhalation reference concentrations for hexavalent and trivalent chromium.

The passage of the Clean Air Act Amendment of 1990 reflects a growing public concern over human exposure to air toxics. The EPA is currently identifying inhalation reference concentrations (RfCs) to be used as risk criteria for determining whether existing or predicted ambient levels of chemicals are above acceptable concentrations. This paper evaluates the risk assessment methods used by the EPA to develop the recently proposed RfC (0.002 micrograms/m3) for both trivalent chromium [Cr(III)] and hexavalent chromium [Cr(VI)]. Based on our evaluation, these RfC values do not appear to have been developed in accordance with standard Agency procedures or classic toxicology methods for setting RfCs. In particular, the "key" study used by the EPA [E. Lindberg and G. Hedenstierna (1983) Arch. Environ. Health 38, 367-374] as the basis for their proposal is not appropriate because it examined only the effects of exposure to chromic acid mist [Cr(VI)], even though most environmental exposure is to Cr(VI) and Cr(III) as a dust. The health hazards of Cr(VI) as an acid mist are significantly different from those associated with Cr(VI) as a dust. Further, the EPA's key study did not evaluate exposure to Cr(III), the toxicity of which is significantly different from both particulate Cr(VI) and chromic acid mist. Finally, the uncertainty factors used to account for data gaps were unusually high, thus providing RfC values equal to or below most naturally occurring environmental levels and standard analytical limits of detection. In this paper, we propose alternative RfCs for Cr(VI) as chromic acid mist and for Cr(VI) as a dust. Based on the Lindberg and Hedenstierna study, we derived an RfC of approximately 0.12 micrograms/m3 for chromic acid mist. An RfC of 1.2 micrograms/m3 is recommended for particulate Cr(VI) based on animal studies that evaluate long-term inhalation exposure to Cr(VI) dust. Due to its low toxicity, an RfC for Cr(III) is not warranted.

Administration, Inhalation↗