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Survey of polynuclear aromatic compounds in oil refining areas.

Air samples in and around refinery areas were collected over a 3-year period. The results of the analysis for polynuclear aromatic compounds listed as priority pollutants by the United States Environmental Protection Agency are presented. The particulate matters in the air were collected on glass fiber filters using high volume samplers. These samples were later Soxhlet extracted with cyclohexane, and then extracted with DMSO/pentane for isolation of the polynuclear aromatic compounds. These extracts were then analyzed using gas chromatography-mass spectrometry for specified polynuclear aromatic compounds. It was found that much higher concentrations of these aromatic compounds were found in one refinery compared to another one. In general, the number of these priority pollutants detected and their concentrations were higher in sites inside the refineries relative to a site outside the refineries.

Journal Article↗

A two-year study of seasonal indoor radon variations in southern Maryland.

The concentrations of indoor radon in the basements of homes located in southern Maryland average about 1.3 times the first floor radon concentrations. Particular geological units tend to be associated with higher indoor radon. In the study area, homes underlain by phyllite were mostly above 4 pCi/liter (the US Environmental Protection Agency 'action level'). Comparative studies between indoor radon and total-gamma aeroradioactivity show that aeroradioactivity can be accurately used to estimate community radon hazards. When combined, geology and aero radioactivity can be used to identify problem homes.

Journal Article↗

Estimating the risks and benefits of pesticides: considering the agroecosystem and integrated pest management in the use of EBDC fungicides on apples.

Calculating the risks and benefits of agricultural pesticides determines whether a pesticide will be registered for use on commodities. Historically, the US Environmental Protection Agency (EPA) has used very conservative estimates of health risks, particularly in the absence of data regarding actual use patterns of the pesticide and actual pesticide residue at the point of food purchase. However, when grower groups and manufacturers were faced with the problem of losing the ethylene bisdithiocarbamate (EBDC) fungicides, they approached EPA offering to provide hard data in place of estimates. Plant pathologists familiar with apple agroecosystems pointed out that different fungicides have highly specific uses in integrated pest management (IPM) programs, and that banning EBDC use on apples would probably raise total pesticide use in apples by compromising the pesticide reductions obtained under existing IPM programs. In addition, an early study showed that use-patterns could significantly reduce the amount of EBDC residue on apples. This approach led to a more realistic appraisal of both risks and benefits of the fungicides, lowering risks and raising benefits. The process ended with a registration prescribing use-patterns which result in minimal residue at harvest, thus providing valuable tools for use in IPM programs.

Journal Article↗

Comparison of chlordimeform and carbaryl using a functional observational battery.

The effects of the formamidine pesticide chlordimeform (CDM), and the carbamate carbaryl (CAR) were compared using a functional observational battery (FOB). The FOB, a series of observations and measurements that can be rapidly administered to toxicant-treated rats, includes home-cage and open-field observations, neuromuscular and sensorimotor tests, and physiological measures. Evaluations were made according to U.S. Environmental Protection Agency testing guidelines so as to determine dose-, time-, and sex-related toxicant effects. Long-Evans hooded rats of both sexes were tested initially and then dosed ip with either vehicle, CDM (1, 25, 56 mg/kg) or CAR (3, 10, 30 mg/kg), and tested at various times after dosing (for CDM 1, 5, 24 hr; for CAR 0.5, 3, 24, 48 hr). Both compounds affected general activity (home-cage and open-field), equilibrium, CNS excitability, and sensory responsiveness. Whereas similar decreases were obtained on rearing, gait, and arousal, there were important qualitative differences in the effects of CAR and CDM on reactions to handling and the reflex tests in that CDM increased excitability and enhanced responses to several stimuli but CAR either had no effect or decreased these measures. Only CDM produced an increase in muscle tone as measured by grip strength, and only CAR produced cholinergic autonomic signs of intoxication. Body weight and temperature were decreased by both compounds. Thus, the profiles of effect produced by these two pesticides could be clearly differentiated using the FOB.

Amidines↗

The induction of bladder stones by terephthalic acid, dimethyl terephthalate, and melamine (2,4,6-triamino-s-triazine) and its relevance to risk assessment.

Terephthalic acid (TPA), dimethyl terephthalate (DMT), and melamine (MA) induced calculi and transitional cell hyperplasia in urinary bladders of rats. A high incidence of calculi was induced in weanling rats, but the incidence was much lower in adult rats ingesting the same dietary concentration of the chemical. The dose-response curves for the induction of urolithiasis in weanling rats were extremely steep, consistent with the fact that the formation calculi can occur in urine that is supersaturated, but not in urine that is undersaturated with respect to the stone components. In the cases of TPA and DMT, stones were composed primarily of calcium terephthalate (CaTPA). By determining the solubility of CaTPA, the concentration of TPA that would be required to achieve urinary saturation was calculated, and a conservative estimate of the amount of TPA or DMT that would have to be absorbed in order to induce calculi was derived. TPA and MA induced bladder tumors in rats in chronic feeding studies. However, it is likely that these tumors were secondary to the development of calculi. TPA and MA are apparently nongenotoxic, and they do not appear to be metabolized. Increased cell replication in the urothelium of the bladder caused by chronic physical injury was probably a major factor in the mechanism of induction of bladder tumors by bladder stones. Bladder neoplasms occurred primarily in the high dose groups, and they were usually, although not invariably, associated with stones. The possibility that stones were passed or were lost during processing of tissues for histopathologic examination could explain the absence of calculi from some of the neoplastic bladders. The formation of bladder calculi is an example of a threshold effect. Although there is strong evidence linking bladder stones with the induction of tumors, the existence of thresholds in chemical carcinogenesis continues to be controversial. A decision by the U.S. Environmental Protection Agency concerning the levels of MA allowed to occur in the food chain indicates that data regarding thresholds, even in the case of urolithiasis, are not being utilized in the risk assessment process.

Animals↗

Sulfur mustard as a carcinogen: application of relative potency analysis to the chemical warfare agents H, HD, and HT.

A relative potency method for assessing potential human health effects from exposures to relatively untested chemicals is presented and documented. The need for such a method in evaluating the carcinogenic potential of the chemical warfare agent sulfur mustard (agent HD) from a limited data base is specifically addressed. The best-estimate potency factor for sulfur mustard relative to benzo[a]pyrene is 1.3, with an interquartile range of 0.6 to 2.9. The method is applied to (1) the estimated fence-boundary air concentrations of mustard during operation of a proposed agent incinerator at Aberdeen Proving Ground (APG), Maryland, and (2) the current approved general population exposure level of 1 X 10(-4) mg HD/m3 and the occupational exposure level of 3 X 10(-3) mg HD/m3. Maximum estimates of excess lifetime cancer risk for individuals at sites along the APG boundary range between 3 X 10(-8) and 1 X 10(-7). Lifetime cancer risk estimates less than or equal to 10(-6) are not now regulated by the U.S. Environmental Protection Agency or the Food and Drug Administration. Maximum estimates of excess lifetime cancer risk assuming daily exposure to the approved standards during the proposed 5 years of incinerator operation are on the order of 10(-5) for the general public and 10(-4) for the worker population. These values are considered upper limit estimates.

Animals↗

Water quality criteria for hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX).

The occurrence of the munitions compound hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in groundwater surrounding Army ammunition plants may result in contamination of local drinking water supplies. RDX exerts its primary toxic effect in humans on the central nervous system, but also involves gastrointestinal and renal effects. Symptomatic effects following acute exposure include hyperirritability, nausea, vomiting, generalized epileptiform seizures, and prolonged postictal confusion and amnesia. Health effects data were analyzed for RDX, and although no controlled human studies exist concerning the acute or chronic toxic effects of exposure to RDX, sufficient animal toxicity data are available to derive an ambient water quality criterion for the protection of human health. This paper summarizes the available literature on metabolism of RDX and human and animal toxicity. Based on noncarcinogenic mammalian toxicity data, and following the methodologies of the U.S. Environmental Protection Agency, an ambient water quality criterion for the protection of human health of 103 micrograms/liter is proposed for ingestion of drinking water and aquatic foodstuffs. A criterion of 105 micrograms/liter is proposed for ingestion of drinking water alone.

Animals↗

Chlorine dioxide and hemodialysis.

In the United States chlorination of potable water supplies has been the standard method of disinfection for about 75 years. In recent times concern has been raised about the propensity of chlorination to introduce potentially carcinogenic trihalomethanes (THM) such as chloroform into finished water. The levels of THM introduced depend on many factors including the quality of the raw water. Numerous community water treatment facilities are experiencing difficulty in meeting current U.S. Environmental Protection Agency standards, and it is likely that the permissible levels may be lowered in the future. An alternative to chlorination which does not generate THM during disinfection is chlorine dioxide, but there are concerns about the acute and chronic toxicity of ClO2 and its disinfection by-products, chlorite and chlorate. Deleterious effects of moderately high levels of these oxychlorines have been demonstrated experimentally on red blood cells, thyroid function, and development in laboratory animals. Adverse effects in controlled prospective studies in humans and in actual use situations in community water supplies have as yet failed to reveal clear evidence of adverse health effects. Among groups who may be at special risk from this suggested alternative are patients who must undergo chronic extracorporeal hemodialysis. The special needs, precautions, and experience to date in regard to finished water are reviewed. Again, very limited human experience has failed to reveal adverse health effects. Further study, caution, and extreme vigilance are indicated, but dialysis patients in carefully controlled facilities may be at no greater risk than the general population.

Animals↗

Water quality criteria for 2,4,6-trinitrotoluene.

The occurrence of the munitions compound 2,4,6-trinitrotoluene (TNT) in groundwater and surface water surrounding U.S. Army ammunition plants may result in contamination of local drinking water supplies. TNT exerts its primary toxic effect in humans on the hematologic system and liver, but it is also known to cause gastrointestinal effects and cataracts. Health effects data were analyzed for TNT and although no controlled human studies exist concerning the acute or chronic toxic effects of exposure to TNT, sufficient animal toxicity data are available to derive an ambient water quality criterion for the protection of human health. This paper summarizes the available literature on metabolism and toxicity of TNT in humans and animals. Based on noncarcinogenic mammalian toxicity data, and following the methodologies of the U.S. Environmental Protection Agency, an ambient water quality criterion for the protection of human health of 135 micrograms/liter is proposed when consumption of both contaminated water and fish is anticipated. For drinking water alone, the proposed criterion is 140 micrograms/liter.

Animals↗

Comparison of water quality criterion and lifetime health advisory for hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX).

The U.S. Environmental Protection Agency (USEPA) has recently recommended a lifetime health advisory (HA) for hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). The purpose of this brief article is to present the basis for the calculation of the HA so that the reader can compare it with a water quality criterion (WQC) that has been proposed (E. L. Etnier, 1989, Regul. Toxicol. Pharmacol. 9, 147-157). In the earlier article, a water quality criterion of 105 micrograms/liter for RDX in drinking water was proposed, and in the present article the methodology by which USEPA calculated a lifetime HA of 2 micrograms/liter is presented. The differences in the derivation of the WQC and the HA are discussed.

Animals↗

Trihalomethanes and maximum contaminant levels: the significance of inhalation and dermal exposures to chloroform in household water.

Our review of the literature on the importance of inhalation and dermal exposures to volatile organic compounds in household water relative to ingestion exposures sought to answer two questions. First, how well do the inhalation and dermal doses predicted by simple models, complex simulations, and measurements agree with one another? And second, what are the implications for the cancer risk from chloroform in household water? The literature yields a coherent and credible range of dose estimates: the ratio of lifetime inhalation dose to lifetime ingestion dose is probably in the range of approximately 0.6 to approximately 1.5, but may be as high as approximately 5.7; and the ratio of lifetime dermal dose to lifetime ingestion dose is probably about approximately 0.3, but may be as high as approximately 1.8. However, because the U.S. Environmental Protection Agency's (EPA's) Cancer Potency Factor (CPF) for inhalation of chloroform is much higher than the CPF for ingestion, the ratios of incremental lifetime cancer risk from inhalation of chloroform to risk from ingestion are much larger than the corresponding ratios for dose. The incremental lifetime cancer risk from chloroform by all three pathways is probably approximately 9 to approximately 21 times the ingestion risk and may be as much as approximately 79 times the ingestion risk. As the EPA reviews the drinking water standard for total trihalomethanes, it is essential that the Agency take account of all exposure pathways in estimating cancer risk.

Administration, Inhalation↗

An abbreviated repeat dose and reproductive/developmental toxicity test for high production volume chemicals.

A novel protocol is described for obtaining preliminary data on repeated dose systemic effects and reproductive/developmental toxicity. The test protocol was developed by a group of experts at the request of the U.S. Environmental Protection Agency (EPA) for use as part of a Screening Information Data Set on high production volume chemicals. Interest in this protocol is shared by several regulatory agencies, including the Organization for Economic Cooperation, the European Community, and the EPA. To validate the study protocol, ethylene glycol monomethyl ether (EGME) was used. After a dosing period of approximately 6 weeks, EGME showed both systemic and reproductive/developmental effects similar to those previously reported using standard protocols. Thus, this test protocol may be used as a screening tool for high production volume chemicals.

Abnormalities, Drug-Induced↗

Comparison of the maximum tolerated dose (MTD) dermal response in three strains of mice following repeated exposure to acrylic acid.

The dermal response of three strains of mice (ICR, C3H and B6C3F1) exposed to repeated doses of 0, 1 or 4% acrylic acid was examined over 13 wk. Microscopic and gross changes to the skin were classified as being indicative of exceeding the maximum tolerated dose (MTD), reaching the MTD, or tolerating the dose based on proposed MTD guidelines established in US Environmental Protection Agency (EPA) Workshops on dermal carcinogenesis bioassays. A significant number of animals in all three strains with repeated exposure to 4% acrylic acid experienced skin irritation that was classified as having reached or exceeded the MTD compared with animals exposed to either 1% acrylic acid or the 0% acrylic acid acetone control. These results were observed within the first 3 wk of exposure, but there was some accommodation to irritation by 8 wk of exposure. Microscopic findings provided a more sensitive index for exceeding MTD than gross observations taken only at autopsy, but generally correlated well for MTD if gross observations were taken at regular intervals during treatment. That is, to set MTD, gross observations could be used if taken over the entire course of the exposure, but using microscopic findings was generally a more reliable or sensitive measure. EPA guidelines suggest that it is inappropriate to conduct a dermal bioassay at concentrations that exceed the MTD. Acrylic acid at 4% in acetone clearly exceeded the MTD based on microscopic or gross observation criteria. At 4%, strain differences were evident by gross observation only, with the ICR strain being less susceptible to irritation than C3H or B6C3F1 strains. These strain differences were not apparent with microscopic examination. Acrylic acid at 1% in acetone, although demonstrating signs of minimal irritation, was fairly well tolerated by all mice in all strains. Thus, acrylic acid at 1% in acetone, one-quarter of the concentration that was in clear excess of the MTD, would be the appropriate dose concentration for lifetime skin studies based on MTD criteria.

Acrylates↗

Single-dose and 13-week repeated-dose neurotoxicity screening studies of chlorpyrifos insecticide.

Chlorpyrifos (CPF), a widely used organophosphate insecticide, was screened for neurotoxic effects in Fischer 344 rats using United States Environmental Protection Agency 1991 guidelines for single-dose and 13-wk repeated dose studies. The studies emphasized a functional observational battery (which included grip performance and hindlimb splay tests), automated motor activity testing and comprehensive neurohistopathology of perfused tissues. Doses of up to 100 mg/kg body weight in corn oil by gavage in the single-dose study and up to 15 mg/kg body weight/day in diet for 13 wk in the repeated dose study were administered. It is known that CPF and other phosphorothionates can be activated to the oxon in local (extrahepatic) tissues. Local activation could possibly cause different effects in different tissues with cholinergic innervation, and thereby create syndromes unique to each phosphorothionate according to their structure. Consequently, the conduct of CPF neurotoxicity screening studies by contemporary guidelines offered opportunity to characterize the CPF over-exposure syndrome in rats. Single-dose high levels of oral exposure to CPF caused a range of clinical signs characteristic of cholinergic overstimulation. Although there was no clinical evidence of wide differences in sensitivity of one cholinergic response versus another, motor dysfunction (incoordination etc.) was more prominent than other signs, for example soiling. Effects were much more apparent in females and regressed over several days. Effects were minimal in the 13-wk study, and there was no evidence of accumulation of toxicity during the 13 wk of daily dietary exposure. Motor activity was decreased at the high dose in males and females at wk 4, but was not significantly different from controls in subsequent weeks. The 'normalization' of motor activity later in the study was interpreted as tolerance to repeated administration of CPF. Comprehensive neuropathological examination revealed no treatment-related lesions in either study.

Administration, Oral↗

Use of quantitative modelling in methylene chloride risk assessment.

The benefits of basing quantitative risk assessment on measures of 'internal dose', i.e. target organ exposures as estimated, for instance, by pharmacokinetic models, have been extensively discussed. Recasting risk assessment methods at the level of internal dose raises novel issues, however, some of which are explored by examining the 1987 revision by the US Environmental Protection Agency (EPA) of its cancer risk assessment for inhaled methylene chloride, which was based on the 1987 pharmacokinetic model results of Andersen and coworkers. The internal dose measure was the daily amount of methylene chloride metabolized by a glutathione-S-transferase pathway per 1 of target organ (liver and lung). Owing to high-dose saturation of a competing detoxification reaction, this metabolic activation is less-than-proportionally active at low exposure levels. For a given inhalation exposure, humans have relatively less metabolic activation than do mice, but this is shown to be a foreseeable consequence of their relatively lower breathing rate, a cross-species difference already accounted for in standard EPA methodology. Indeed, many species differences in the rates and tempos of physiological processes evince regular 'scaling' relationships across differently sized mammals. EPA's practice of scaling carcinogen doses by body surface area for cross-species extrapolation, often viewed as a correction for metabolic activation, is shown to be more reasonably regarded as an accommodation for the more general species variation in the pace of physiological processes underlying both pharmacokinetics and the carcinogenic response to internal doses. Under this view, the issue of cross-species dose scaling is not obviated by the use of pharmacokinetics.

Administration, Inhalation↗

Is EPA's radium-226 drinking water standard justified?

The U.S. Environmental Protection Agency's (EPA) proposed drinking water standard for radium-226 (226Ra) of 5 pCi/l is evaluated according to its health basis and carcinogenic implications. Proposed health risks of 226Ra in drinking water by other leading theoreticians (Evans, Gofman-Tamplin and Peterson) are also considered in light of the EPA proposal. It is concluded that the EPA proposal to raise the standard for 226Ra in drinking water is not justified on the basis of present knowledge of 226Ra carcinogenic effects.

Body Burden↗

NACA overview on assessment of mixer-loader-applicator exposure to pesticides. National Agricultural Chemical Association.

An overview is given of the involvement of the National Agricultural Chemical Association (NACA) in the research of field worker exposure and in the drafting of a protocol for performing exposure studies. Specific field methods are discussed and criteria for the utilization of biological monitoring are given. A generic exposure data base is being developed together with the Environmental Protection Agency (EPA).

Absorption↗

Estimation of a lifetime unit lung cancer risk for benzo(a)pyrene based on tumour rates in rats exposed to coal tar/pitch condensation aerosol.

Female Wistar rats were exposed to coal tar/pitch condensation (CTP) aerosol containing either 20 or 46 micrograms/m3 benzo(a)pyrene (BaP) among other polycyclic aromatic hydrocarbons (PAH) 17 h/day and 5 days/week for 10 or 20 months followed by a clean air period of up to 20 or 10 months, respectively. Based on the inhaled BaP, given as BaP exposure concentration multiplied by the total exposure time, the cumulative dose of inhaled BaP of the 4 exposure groups was 71, 142, 158 and 321 mg BaP/m3 x h and the corresponding lung tumour rates were 4.2, 33.3, 38.9 and 97.2%. There was no lung tumour in the control group. Using the US Environmental Protection Agency (EPA) linearized multistage model, the lifetime lung tumour risk for rats exposed to 1 microgram/m3 BaP as a constituent of a complex PAH mixture may be 2% or correspondingly 2 per 100,000 with a BaP concentration of 1 ng/m3. The estimation of the unit lung cancer risk for BaP based on epidemiological data from coking plants was 7-9%.

Administration, Inhalation↗