Toxicology and Industrial Health

Burg, Jeanne R. ;Gist, Ginger L.

doi: 10.1177/074823379801400301pmid: 9569445

The purpose of the National Exposure Registry is to assess the long-term health consequences to a general population from long-term, low-level exposures to specific substances in the environment. This study investigates the health outcomes of 1, 143 persons (1,127 living, 16 deceased) living in south central Texas who had documented environmental exposure to benzene (up to 66ppb) in tap water. As with all subregistries, face-to-face interviews were used to collect self-reported information for 25 general health status questions. Using computer-assisted telephone interviewing, the same health questions were asked I year (Followup 1, F1) and 2 years later (Followup 2, F2). The health outcome rates for Baseline and Followup I and 2 data collections for the Benzene Subregistry were compared with national norms, that is, the National Health Interview Survey (NHIS) rates. For at least one of the three reporting periods, specific age and sex groups of the Benzene Subregistry population reported more adverse health outcomes when compared with the NHIS population, including anemia and other blood disorders, ulcers, gall bladder trouble, and stomach or intestinal problems, stroke, urinary tract disorders, skin rashes, diabetes, kidney disease, and respiratory allergies. Statistically significant deficitsfor the Benzene Subregistry population overall were found for asthma, emphysema, or chronic bronchitis; arthritis, rheumatism, or other joint disorders; hearing impairment; and speech impairment. No statistically significant differences between the two populations were seen for the outcomes hypertension; liver disease; mental retardation; or cancer. These results do not identify a causal relationship between benzene exposure and adverse health effects; however, they do reinforce the need for continued followup of registrants.

De Rosa, Christopher T. ;Stevens, Yee-Wan ;Johnson, Barry L.

doi: 10.1177/074823379801400302pmid: 9569446

Frantz, Stephen W. ;Ballantyne, Bryan ;Leung, Hon-Wing

doi: 10.1177/074823379801400303pmid: 9569447

2,4-Pentanedione (2,4-PD; CAS No. 123-54-6), an industrial chemical, was investigated for its comparative pharmacokinetics in male Fischer 344 rats by a single intravenous (IV) injection of (4.3, 43, 148.5, and 430 mg/kg), or a 6-hr nose-only inhalation exposure (400 ppm) to 14C-2,4-PD. For the IV route, the plasma concentration of 14C-2,4-PD derived radioactivity declined in a biexponential fashion. The overall form of the 14C plasma concentration-time curves and derived pharmacokinetic parameters indicated that dose-linear kinetics occurred in the IV dose range 4.3-148.5 mg/kg, but not with 430 mg/kg. Metabolism of 2,4-PD was quite rapid as the concentration of unmetabolized 2,4-PD declined steadily to undetectable after 8 hr. 14C-2,4-PD derived radioactivity was eliminated mainly as 14CO 2 and in urine. For the 4.3, 43 and 148.5 mg/kg doses 14CO2 elimination was relatively constant (36.8, 38.8 and 42.3% in 48 hr samples respectively) and greater than urinary excretion (17.9, 14.3 and 29.6% ; 48 hr specimens). At 430 mg/kg IV there was a reversal of the excretion pattern, with urine 14C excretion (54.7%) becoming greater than that for 14CO2 (27.3%). Excretion in expired volatiles and feces was small. Radiochromatograms of urine showed free 2,4-PD in the 12 hr sample, together with 7 other metabolites. Free 2,4-PD and 6 of the metabolites decreased or were not detectable in a 24 or 48 hr urine sample, but one peak (retention 7.9 min) increased progressively to become the major fraction (97%). Nose-only exposure to 400 ppm 14C-2, 4-PD produced a mean decrease in breathing rate of 20.1 %, which was constant and sustained throughout exposure, due to a lengthening of the expiratory phase of the respiratory cycle. 14C-2,4-PD was rapidly absorbed during the first 3 hr of exposure, then began to plateau, but did not reach a steady state. Postexposure elimination of 14C from plasma followed a biexponential form with a t1/2 for the terminal disposition phase of 30.72 hr. Plasma unmetabolized 2,4-PD was present throughout the whole of the exposure phase, but was significantly less than total 14C. Postexposure, plasma unmetabolized 2,4-PD declined rapidly to undetectable concentrations by 12 hr. Radiolabel excretion was approximately equivalent in urine (37.6%) and expired 14CO 2 (36.3%). Urine radiochromatograms showed a minor 2,4-PD contaminant (0.6-5.9% over 48 hr), along with 7 other peaks probably representing metabolites. As with the 148.5 mg/kg IV dose, the major metabolite peak was at 7.8 min retention, increasing from 41.1% (12 hr) to 62.8% (48 hr). Immediately postexposure, radioactivity was present in all tissues examined, but on a concentration basis (μg equiv/g) there was no preferential accumulation of 14C in any tissue or organ. On a total organ basis, highest contents were in liver and kidney, presumably related to the metabolism and excretion of 2,4-PD. By 48 hr postexposure, concentrations had decreased in all tissues except fat, presumably due to the lipophilicity of 14C residues. The profile of the plasma-time radioactivity curves, and the presence of residual radioactivity in tissues at 48 hr postexposure, suggests that a cumulative process could occur with frequent repeated exposures.

Caldwell, Jane C. ;Woodruff, Tracey J. ;Morello-Frosch, Rachel ;Axelrad, Daniel A.

doi: 10.1177/074823379801400304pmid: 9569448

Relatively little is known about the spectrum of health effects, and the scope and level of ambient air concentrations of those pollutants regulated under the Clean Air Act as "hazardous air pollutants. " The U.S. Environmental Protection Agency's (USEPA) Cumulative Exposure Project uses currently available emissions inventories, from a variety of source types, and an atmospheric dispersion model to provide estimates of ambient concentrations for 148 hazardous air pollutants (HAPs) in over 60,000 census tracts for the year 1990. This paper uses currently available hazard information for those pollutants and provides a database of potential regulatory threshold concentrations of concern, or "benchmark concentrations, " and a methodology for prioritizing and characterizing the quality of the data. In order to demonstrate application of the database and prioritization scheme to outputs from the Cumulative Exposure Project, comparisons were made with the maximum modeled concentration of each individual hazardous air pollutant across the census tracts. Of the 197 benchmark concentrations for cancer and non-cancer (long- and short-term exposures) effects compiled for the study, approximately one half were exceeded with a predominance of exceedance of cancer benchmarks. While the number of benchmark concentrations available to fully characterize potential health effects of these pollutants was limited (approximately 80 percent of HAPs identified as cancer concerns had benchmark concentrations for cancer and 50 percent of all HAPs had non-cancer benchmark concentrations) and there was greater uncertainty in derivation of maximum modeled air concentrations than other levels, the comparison between the two was a useful approach for providing an indication of public health concern from hazardous air pollutants.

Chou, C-H Selene Jen ;Williams-Johnson, Mildred

doi: 10.1177/074823379801400305pmid: 9569449

The Agency for Toxic Substances and Disease Registry (ATSDR) uses substance-specific minimal risk levels (MRLs) to assist in evaluating public health risks associated with exposure to hazardous substances. By definition, "MRLs are estimates of daily human exposure to a chemical that are likely to be without an appreciable risk of adverse noncancer health effects over a specified duration of exposure. " MRLs serve as screening levels for health assessors to identify contaminants and potential health effects that may be of concern for population living near hazardous waste sites and chemical releases. MRLs for each substance are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) exposure durations, and for the oral and inhalation routes of exposure. The MRLs are derived from data compiled from a current comprehensive literature search and are presented in ATSDR's toxicological profile for that substance. In this paper we outline ATSDR's guidance for evaluating the neurological end point as discussed in the agency's toxicological profiles. Ranking neurological effects into less serious and serious categories and applying this procedure to the derivation of health guidance values or MRLs are also described. Specific examples of ATSDR MRLs based on neurological effects are presented.

Rana, Suresh V.S. ;Rastogi, Nidhi

doi: 10.1177/074823379801400306pmid: 9569450

Hepato-toxicity of cadmium in alloxan induced diabetic rats has been studied by estimating a few enzymes viz serum glutamic oxalacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase and γ-glutamyltranspeptidase. Present results suggest that cadmium manifests difterent effects in normal and diabetic rats. Insulin therapy helps in restoring the liver function. It is suggested that an isozyme of cytochrome P450 that appears in diabetic rats might be responsible for altered toxicity of cadmium.