Biomedical subjects

B L Finley

Publications and source records attributed to B L Finley.

At least 37 records · Page 2Linked to original sources

PubMed1994

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↗

PubMed1994

Urinary excretion of chromium following ingestion of chromite-ore processing residues in humans: implications for biomonitoring.

Biomonitoring programs for urinary chromium (Cr) typically attempt to evaluate occupational exposure via the inhalation route. This study investigated whether Cr can be detected in the urine of people following the ingestion of soils that contain relatively high concentrations of chromium in chromite ore processing residue (COPR). To evaluate the reasonableness of using urinary monitoring to assess environmental exposure, six volunteers ingested 400 mg of soil/day (low-dose group), two others ingested 2.0 g of soil/day (high-dose group) for 3 consecutive days, and one person ingested a placebo on each of 3 days. The soil and COPR mixture contained concentrations of total chromium (Cr) and hexavalent chromium [Cr(VI)] of 103 +/- 20 and 9.3 +/- 3.8 mg/kg, respectively. Therefore, the low-dose group ingested 41 micrograms Cr/day [including 3.7 micrograms Cr(VI)] and the high-dose group ingested 206 micrograms Cr/day [including 18.6 micrograms Cr(VI)] on each of 3 consecutive days. All urine samples were collected and analyzed individually for total Cr on the day prior to dosing, during the 3 days of dosing, and up to the first void 48 h after the last dose. No significant increases in urinary Cr excretion were found when background excretion data were compared with data following each of the 3 days of dosing or in daily mean urine concentrations of the high- vs the low-dose groups. It appears that Cr present in a soil and COPR mixture at Cr doses up to 200 micrograms/day is not sufficiently bioavailable for biomonitoring of urine to be informative.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1994

Exposure assessment: then, now, and quantum leaps in the future.

Health risk assessments have become so widely accepted in the United States that their conclusions are a major factor in many environmental decisions. Although the risk assessment paradigm is 10 years old, the basic risk assessment process has been used by certain regulatory agencies for nearly 40 years. Each of the four components of the paradigm has undergone significant refinements, particularly during the last 5 years. A recent step in the development of the exposure assessment component can be found in the 1992 EPA Guidelines for Exposure Assessment. Rather than assuming worst-case or hypothetical maximum exposures, these guidelines are designed to lead to an accurate characterization, making use of a number of scientific advances. Many exposure parameters have become better defined, and more sensitive techniques now exist for measuring concentrations of contaminants in the environment. Statistical procedures for characterizing variability, using Monte Carlo or similar approaches, eliminate the need to select point estimates for all individual exposure parameters. These probabilistic models can more accurately characterize the full range of exposures that may potentially be encountered by a given population at a particular site, reducing the need to select highly conservative values to account for this form of uncertainty in the exposure estimate. Lastly, our awareness of the uncertainties in the exposure assessment as well as our knowledge as to how best to characterize them will almost certainly provide evaluations that will be more credible and, therein, more useful to risk managers.(ABSTRACT TRUNCATED AT 250 WORDS)

Environmental Exposure↗

PubMed1994

Development of a standard soil-to-skin adherence probability density function for use in Monte Carlo analyses of dermal exposure.

It has recently been suggested that "standard" data distributions for key exposure variables should be developed wherever appropriate for use in probabilistic or "Monte Carlo" exposure analyses. Soil-on-skin adherence estimates represent an ideal candidate for development of a standard data distribution: There are several readily available studies which offer a consistent pattern of reported results, and more importantly, soil adherence to skin is likely to vary little from site-to-site. In this paper, we thoroughly review each of the published soil adherence studies with respect to study design, sampling, and analytical methods, and level of confidence in the reported results. Based on these studies, probability density functions (PDF) of soil adherence values were examined for different age groups and different sampling techniques. The soil adherence PDF developed from adult data was found to resemble closely the soil adherence PDF based on child data in terms of both central tendency (mean = 0.49 and 0.63 mg-soil/cm2-skin, respectively) and 95th percentile values (1.6 and 2.4 mg-soil/cm2-skin, respectively). Accordingly, a single, "standard" PDF is presented based on all data collected for all age groups. This standard PDF is lognormally distributed; the arithmetic mean and standard deviation are 0.52 +/- 0.9 mg-soil/cm2-skin. Since our review of the literature indicates that soil adherence under environmental conditions will be minimally influenced by age, sex, soil type, or particle size, this PDF should be considered applicable to all settings. The 50th and 95th percentile values of the standard PDF (0.25 and 1.7 mg-soil/cm2-skin, respectively) are very similar to recent U.S. EPA estimates of "average" and "upper-bound" soil adherence (0.2 and 1.0 mg-soil/cm2-skin, respectively).

Adhesiveness↗

PubMed1993

Evaluating the adequacy of maximum contaminant levels as health-protective cleanup goals: an analysis based on Monte Carlo techniques.

At many sites in the United States, health-based remediation goals for contaminated groundwater have been set at levels far below USEPA's drinking water standards (i.e., maximum contaminant levels or MCLs). This is due to the fact that, while the USEPA must often consider technical and economic factors (e.g., cost of compliance, risk/benefit analysis) when setting MCLs for public water systems, cleanup goals for contaminated groundwater are often based solely on conservative "point" estimates of exposure. One of the more recent refinements in the risk assessment process is the use of ranges of exposure estimates or "probability density functions" (PDFs), rather than fixed point estimates, to estimate exposure and chemical uptake. This approach provides a more thorough description of the range of potential risks, rather than a single "worst-case" value, and allows one to understand the conservatism inherent in assessments based on regulatory default parameters. This paper uses a number of PDFs and the Monte Carlo technique to assess whether the USEPA's MCLs for drinking water are sufficiently low to protect persons exposed to these levels. A case study involving daily exposure to tapwater containing MCL concentrations of tetrachloroethylene, chloroform, bromoform, and vinyl chloride is presented. Several direct and indirect exposure pathways are evaluated, including inhalation and dermal contact while showering, direct ingestion, and inhalation of emissions from household fixtures and appliances. PDFs for each exposure factor are based on the most recent and applicable data available. Our analysis indicates that the estimated increased cancer risks at the 50th and 95th percentile of exposure are within the range of increased cancer risks typically considered acceptable at Superfund sites (10(-4)-10(-6)). These results suggest that, at least for some chemicals, groundwater need not be cleaned-up to concentrations less than drinking water standards (i.e., MCLs) to protect human health.

Air Pollutants↗

PubMed1993

Designing a biological monitoring program to assess community exposure to chromium: conclusions of an expert panel.

The possible benefits of biological monitoring of large groups of people potentially exposed to environmental contaminants has become an area of much interest in recent years. Because chromite-ore processing residue has been found in some soils in northern New Jersey, urinary chromium monitoring of people in the community was evaluated as a potentially useful tool. In an attempt to identify those who could be exposed and to quantify the magnitude of exposure to the chromium in these soils, the New Jersey Department of Health (NJDOH) initiated a public health screening project. In 1992, the NJDOH proposed to evaluate over 4000 people who lived or worked near these sites. Volunteers were administered a questionnaire and were given a limited physical examination, and a single spot urine sample was collected. Because of the difficulties in using urinary chromium to assess low-level exposure and the potential implications of any regulatory decisions that could be based on the results of this project, a panel of experts was convened to evaluate the protocol. The panel consisted of five scientists and physicians with expertise in toxicology, dermatology, epidemiology, biological monitoring, and analytical chemistry. Like a World Health Organization group, the panel concluded that although urine biomonitoring can be useful in evaluating high levels of exposure to chromium, it is not reliable for assessing low-level exposure similar to that which may have occurred in northern New Jersey. The panel also noted that when urinary biomonitoring is to be used to assess the public's possible exposure, a large number of precautions must be taken to ensure the accuracy and usefulness of the results. The single most important recommendation was to collect a second, and perhaps a third, spot urine (or 24-h urine) sample before concluding that a person may be routinely overexposed. These suggestions are applicable to designing a biomonitoring program for nearly any environmental contaminant to which a community may be exposed. A review of scientific literature associated with biological monitoring of chromium is provided.

Absorption↗

PubMed1993

Using human sweat to extract chromium from chromite ore processing residue: applications to setting health-based cleanup levels.

Chromite ore processing residue (COPR) containing measurable levels of hexavalent and trivalent chromium. [Cr(VI) and Cr(III), respectively] has been used to fill in low-lying areas in Hudson County, N.J. While it has been demonstrated that direct dermal contact with solutions containing Cr(VI) may elicit allergic contact dermatitis (ACD) in previously sensitized individuals, it is unknown to what degree skin moisture may solubilize Cr(VI) from COPR adhering to skin. An accurate estimate of this extraction potential is necessary to establish COPR concentrations of Cr(VI) and Cr(III) that are protective of eliciting ACD in sensitized individuals. The purpose of this study was to measure the extractable fraction of Cr(VI) and total chromium [Cr(III) and Cr(VI)] in soils impacted by COPR using human sweat as the extractant. Human sweat was collected from seven male volunteers. Samples of COPR material containing the following Cr(VI) and total chromium concentrations were collected: Cr(VI), 16, 136, and 1240 ppm; total chromium, 932 and 6660 ppm. The samples were sieved to obtain a uniform particle size < 500 microns. The samples were then mixed with human sweat at 30 degrees C for 12 h, after which the sweat was filtered and analyzed to determine the dissolved concentration of Cr(VI) and total chromium. The data from these analyses show that no detectable levels (limit of detection = 0.010 ppm) of Cr(VI) were leached from COPR containing 16 ppm Cr(VI). At Cr(VI) concentrations of 136 and 1240 ppm, less than 0.1% of the Cr(VI) present in the COPR sample was extracted into sweat, and sweat concentrations were 0.133 ppm Cr(VI) or less. Similarly, the amount of Crtotal extracted was 0.3% or less at COPR concentrations as high as 6600 ppm Crtotal, and sweat concentrations were 2.3 ppm Crtotal or less. If a minimum concentration of 10 ppm (Bagdon and Hazen, 1991) to 54 ppm (Paustenbach et al., 1992) Cr(VI) in sweat is required to elicit an ACD response in chromium-sensitive individuals, the current study results suggest that a COPR Cr(VI) concentration of at least 10,000-54,000 ppm would be required to elicit ACD. If 500 ppm (or greater) of solubilized Cr(III) is required to elicit an ACD response (NJDEPE, 1992a), then a COPR concentration of 250,000 ppm Cr(III) or greater would be required to elicit an allergic response. These results suggest that ACD is unlikely to occur as a result of environmental exposure to the COPR.

Adult↗

PubMed1992

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↗

PubMed1992

Review of the allergic contact dermatitis hazard posed by chromium-contaminated soil: identifying a "safe" concentration.

At least 200 sites in the United States contain soil with elevated levels of trivalent and hexavalent chromium [Cr(III) and Cr(VI)]. Although the potential cancer hazard posed by airborne Cr(VI) has been the primary concern for these sites, a soil cleanup standard based on the potential elicitation of allergic contact dermatitis has been proposed for sites in Hudson County, N.J. This paper describes the rationale for identifying a soil concentration of Cr(VI) that should not pose an allergic contact dermatitis hazard-even in sensitized persons. A literature review of eight published patch test studies that evaluated the allergic response to potassium dichromate was conducted. These studies were evaluated for clinical and statistical relevance in establishing a threshold dose of Cr(VI) to which no more than 10% of the subpopulation sensitized to chromium would respond, and that would protect at least 99.84% of the general population. Although each of the studies had certain methodological limitations when evaluated against current test methods, the data set proved useful for deriving an estimated threshold. Using computer data-fitting techniques based on truncated lognormal distributions, a weighted mean 10% threshold of approximately 150 ppm potassium dichromate or 54 ppm Cr(VI) was identified for the eight studies. Due to the types of limitations noted for these studies, this threshold is likely to be somewhat conservative. Test results have shown that between 5 and 10% of the Cr(VI) at concentrations less than about 500 ppm are released from a soil matrix into an isotonic saline solution simulating sweat. Using human sweat as the extractant, it has been shown that only 0.1% of the CR(VI) at concentrations of approximately 1,000 ppm are released from a soil matrix into sweat. Based on 10% solubilization of soil-bound Cr(VI) and the results of our statistical analysis of previous threshold studies, a concentration of approximately 350 to 500 ppm Cr(VI) in soil should be sufficiently low to protect virtually all exposed people, including children, from chromium-induced allergic contact dermatitis.

Chromium↗

PubMed1991

The potential inhalation hazard posed by dioxin contaminated soil.

Mathematical models and field data were used to estimate the airborne concentrations of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) vapor and particulates which could originate from soil containing 100 ppb TCDD. The model of Jury et al. (1983) and the box approach were used to predict the concentration of TCDD vapor from soil. The daily soil temperature was assumed to vary between 20 degrees C and 40 degrees C for six months of the year to account for diurnal warming and cooling of the soil. The depth of contamination was 50 mm. The model predicted average vapor flux rate for TCDD from soil for this temperature profile was 1.5 x 10(-14) mg/sec-cm2. The upper-bound estimates of the TCDD vapor concentration on-site at 40 degrees C and 20 degrees C were 2.5 pg/m3 and 1.8 pg/m3, respectively. Using a recently proposed unit risk value (URV) of 2.9 x 10(-6) (pg/m3)-1 [slope factor = 1.0 x 10(-14) (mg/kg-day)-1], the maximum plausible cancer risk is about 1 x 10(-5). If one accepts the EPA URV of 3.3 x 10(-5) (pg/m3)-1 (slope factor = 1.2 x 10(-13) (mg/kg-day)-1), then the risk is no greater than 1 x 10(4). A maximum TCDD vapor concentration of 0.21 pg/m3 was predicted 100 meters downwind (for summer days). The on-site concentration of TCDD in suspended particulate was estimated to be 1.4 pg/m3 (based on a TSP level of 0.07 mg/m3 from site soil). For persons exposed to vapors and particulates about 100 meters off-site, the exposure was about 10-fold less.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1990

The current practice of health risk assessment: potential impact on standards for toxic air contaminants.

Since the Bhopal incident, the public has placed pressure on regulatory agencies to set community exposure limits for the dozens of chemicals that may be released by manufacturing facilities. More or less objective limits can be established for the vast majority of these chemicals through the use of risk assessment. However, each step of the risk assessment process (i.e., hazard identification, dose-response assessment, exposure assessment, and risk characterization) contains a number of pitfalls that scientists need to avoid to ensure that valid limits are established. For example, in the hazard identification step there has been little discrimination among animal carcinogens with respect to mechanism of action or the epidemiology experience. In the dose-response portion, rarely is the range of "plausible" estimated risks presented. Physiologically based pharmacokinetic (PB-PK) models should be used to understand the difference between the tissue doses and the administered dose, as well as the difference in target tissue concentrations of the toxicant between rodents and humans. Biologically-based models like the Moolgavkar-Knudson-Venzon (MKV) should be developed and used, when appropriate. The exposure assessment step can be significantly improved by using more sensitive and specific sampling and analytical methods, more accurate exposure parameters, and computer models that can account for complex environmental factors. Whenever possible, model predictions of exposure and uptake should be validated by biological monitoring of exposed persons (urine, blood, adipose) or by field measurements of plants, soil, fish, air, or water. In each portion of an assessment, the weight of evidence approach should be used to identify the most defensible value. In the risk characterization, the best estimate of the potential risk as well as the highest plausible risk should be presented. Future assessments would be much improved if quantitative uncertainty analyses were conducted. Procedures are currently available for making future assessments. By correcting some of these shortcomings in how health risk assessments have been conducted, scientists and risk managers should be better able to identify scientifically appropriate ambient air standards and emission limits.

Air Pollutants↗

PubMed1988

Increased cholesterol epoxide hydrolase activity in clofibrate-fed animals.

Cholesterol epoxide hydrolase (mCE) is a microsomal enzyme that hydrolyzes cholesterol-5,6-epoxides (CE) to cholestanetriol (CT). In the present study, hepatic mCE activity was measured in mice pretreated with several different xenobiotics known to induce a variety of hepatic drug-metabolizing enzymes. Only the phenoxyacetate hypolipidemics (clofibrate and ciprofibrate, included in the diet for 14 days) were found to increase hepatic mCE activity (1.8-fold increase). Clofibrate administration also increased rabbit hepatic (2.9-fold increase) and rat and rabbit renal mCE activity (1.5- and 2.3-fold increase respectively). On a subcellular level, mCE activities in rabbit nuclear and light mitochondrial fractions were increased (3.3- and 1.8-fold increase respectively), whereas activities in the cytosolic and heavy mitochondrial fractions were unchanged. In rabbits, clofibrate administration enhanced the hepatic microsomal hydrolysis of CE without increasing the hydrolysis of arene epoxides (benzopyrene-4,5-oxide) or fatty acid epoxides (methyl cis-9,10-epoxystearate). Increase of tissue mCE activity may significantly enhance tissue CT levels. In this light, it is worth noting similarities in the mechanisms of hypocholesterolemic action caused by clofibrate or CT administration.

Animals↗

PubMed1986

Substrate-selective induction of rabbit hepatic UDP-glucuronyltransferases by ethanol and other xenobiotics.

Male New Zealand white rabbits were treated with various inducers of hepatic metabolism enzymes to characterize the induction of UDP-glucuronyltransferase (UDP-GT) enzymes. Rabbits were pretreated with phenobarbital, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), 3-methylcholanthrene, beta-naphthoflavone, Aroclor 1254, ethanol, trans-stilbene oxide, pregnenolone-16 alpha-carbonitrile, or clofibric acid. Hepatic microsomes from treated and control animals were incubated with the GT1-type substrates, p-nitrophenol and 1-naphthol; the GT2-type substrate, morphine; and the steroid substrate, estrone. Compared to the rat, the rabbit was particularly resistant to UDP-GT induction. Ethanol was the most potent inducer for both GT1 and GT2 activities, but it failed to induce steroid (estrone, estradiol, and testosterone) UDP-GT activities. Ethanol pretreatment increased oxazepam-GT but it decreased bilirubin-GT activity. 3-Methylcholanthrene (3MC) and beta-naphthoflavone (BNF) are the prototypic GT1 inducers in the rat, but 3MC caused no induction of GT1 activity and BNF caused induction of both GT1 and GT2 activities in the rabbit. None of the xenobiotic pretreatments increased the hepatic microsomal glucuronidation of estrone. These results demonstrate that the induction of UDP-GT activities, and the use of this phenomenon to classify UDP-GT forms, is somewhat species-specific and cannot necessarily be extrapolated from rats to other species. In addition, the substrate selectivity of ethanol-induced microsomal UDP-GT was established.

Animals↗

PubMed1983

Ethanol as an inducer of UDP-glucuronyltransferase: a comparison with phenobarbital and 3-methylcholanthrene induction in rabbit hepatic microsomes.

In this report we have examined the ability of ethanol to induce UDP-glucuronyltransferase activity in male rabbits using p-nitrophenol as substrate. The rabbit was found to be an excellent species for studies of ethanol induction since almost 3-fold increases in activity were observed relative to controls. Ethanol induction of p-nitrophenol UDP-glucuronyltransferase activity was even greater than induction by 3-methylcholanthrene, the prototypic inducer of this type of activity. Thus, the rabbit shows promise for studies of UDP-glucuronyltransferase isozymes that are induced by chronic ethanol consumption.

Animals↗

PubMedDate not supplied

Stereoselective glucuronidation as a probe of induced forms of UDP-glucuronyltransferase in rabbits.

Stereoselective glucuronidation of the chiral drug oxazepam by hepatic microsomes from rabbits pretreated with various inducers was used to characterize induced UDP-glucuronyltransferase (GT) enzymes. The enzymes were induced by pretreatment of rabbits with phenobarbital, DDT, 3-methylcholanthrene, beta-naphthoflavone, ethanol, trans-stilbene oxide, pregnenolone-16 alpha-carbonitrile, Aroclor 1254, and clofibric acid. Hepatic microsomes from induced and control animals were incubated with racemic oxazepam and the activator, Lubrol PX. Relative amounts of the diastereomeric beta-glucuronides were determined by HPLC. Significant differences were found in enantiomeric selectivity among the microsomes from rabbits pretreated with different inducers. The largest difference in diastereomeric glucuronide ratios observed was between control (R/S = 0.76) and beta-naphthoflavone-induced microsomes (R/S = 1.41). This demonstrated a significant change in enantiomeric selectivity by the enzymes, changing from preference for the S enantiomer in controls to its R antipode after induction. Differences in stereoselectivity between two members of a class of inducers such as 3-methylcholanthrene (R/S = 1.16) and beta-naphthoflavone (R/S = 1.41), provided evidence for possible distinctions between these similar inducers. Inducers of GT1 UDP-glucuronyltransferase enzyme forms, such as 3-methylcholanthrene, beta-naphthoflavone, and Aroclor 1254, did not increase the rate of formation of oxazepam glucuronides. All other inducers except DDT increased the rate of oxazepam glucuronidation by 20-53% with the highest rate (0.23 nmol/min X mg protein) occurring after trans-stilbene oxide induction. UDP-N-acetylglucosamine was also used as an activator to provide a comparison of the Lubrol-activated microsomes with the endogenous activator. Relative differences among inducers were approximately the same with both activators.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Urinary excretion of chromium by humans following ingestion of chromium picolinate. Implications for biomonitoring.

This study investigated the variability in urinary chromium (Cr) excretion following the ingestion of Cr picolinate by human volunteers. A pharmacokinetic model was used to estimate the bioavailability of Cr from ingested Cr picolinate using known distribution patterns and elimination rates of Cr by humans. The possible advantages of using sequential, individual spot, or 24-hr urine sample collection for biomonitoring of Cr exposure were examined. Background concentrations of urinary Cr determined from the spot samples in this study compared well with values reported by others. The variability in urinary excretion of Cr in untreated volunteers indicated that it is virtually impossible to distinguish exposures to most occupational and virtually all environmental exposures to Cr. Sequential urine sampling was found superior to both 24-hr and spot urine collection for indicating exposure to Cr picolinate. The extent of absorption of Cr from the picolinate matrix in the gastrointestinal tract was 2.80 +/- 1.14% (SD). It was estimated that 10 mg of soil containing between 7,400 and 52,000 mg Cr(III)/kg would have to be ingested by an adult to result in urinary excretion of Cr clearly above the upper bound of Cr in urine from background populations (1.8 microgram Cr/liter), depending on certain assumptions regarding bioavailability. This study supports the results of other recent work that demonstrated urinary excretion of Cr resulting from low-level environmental exposure is unlikely to be distinguished from that resulting from dietary uptake.

Administration, Oral↗

PubMedDate not supplied

Refined exposure assessment for ingestion of tapwater contaminated with hexavalent chromium: consideration of exogenous and endogenous reducing agents.

Laboratory studies were conducted to determine how rapidly and completely chromium (VI) [Cr(VI)] is reduced upon contact with common beverages mixed with tapwater. Studies were performed for five common beverages (coffee, tea, orange juice, Kool Aid, and powdered lemonade) spiked with either 10 or 50 mg Cr(VI)/l. The concentrations of Cr(VI) were measured at several time intervals for up to four hours. It was demonstrated that each of these beverages had the capacity to reduce a concentration of > or = 8 mg Cr(VI)/l within a 15-minute time frame, and that continued monitoring of the beverages revealed greater reduction of the Cr(VI). These findings are consistent with the observation that many foods and beverages, as well as endogenous body fluids such as saliva and gastric juices, are capable of reducing substantial quantities of Cr(VI) to Cr(III). Our exposure assessment shows that the estimated high-end ingested dose of Cr(VI) from tapwater at both 1 and 5 mg Cr(VI)/l is generally two to three orders of magnitude below doses shown to have no adverse health effect in animal studies. When considered in conjunction with studies demonstrating that the reductive capacity of gastric juices may exceed 50 mg Cr(VI) daily, these observations suggest that little or no Cr(VI) is likely to be absorbed orally at a reasonable water concentration of Cr(VI), since tapwater is bright yellow at 5 mg Cr(VI)/l.

Adult↗

PubMedDate not supplied

Assessment of airborne hexavalent chromium in the home following use of contaminated tapwater.

Field studies were conducted to estimate the plausible uptake of hexavalent chromium [Cr(VI)] aerosols inhaled during indoor residential use of a shower or an evaporative cooler supplied with water containing Cr(VI). In the evaporative cooler study, water concentrations of 20 mg Cr(VI)/L did not produce an increased concentration of airborne Cr(VI). The indoor air concentration of Cr(VI), measured over 24 hours of use, was 0.3-2.7 ng/m3, about the same as the concurrent outdoor concentrations. In the shower study, the average airborne concentrations of Cr(VI) aerosols at breathing-zone height ranged from 87 to 324 ng Cr(VI)/m3 when the water concentration of Cr(VI) was 0.89 to 11.5 mg/L. The Cr(VI) concentration in air was correlated directly to water concentration. The lifetime average daily doses and incremental cancer risk estimates corresponding to 30-year residential exposures were calculated using the measurements in this study and published exposure guidelines. The plausible upperbound lifetime cancer risk associated with continuous exposure to "background" Cr(VI) in outdoor air was estimated at 6.9 per million for a person exposed during ages 0-30, and 4.0 per million for ages 30-60. Similarly estimated upperbound cancer risks due to inhalation of shower aerosols from water containing 2-10 mg Cr(VI)/L over the same exposure period ranged from 0.9 to 5.5 per million. Our calculations demonstrate that shower aerosols do not contribute appreciably to background Cr(VI) exposures and risks, even at concentrations exceeding 2 mg Cr(VI)/L, which exhibit a discernible and unaesthetic yellow color that may limit the potential for long-term exposures of this type. We conclude that exposure to indoor aerosols from water containing Cr(VI) is unlikely to create a health hazard at concentrations up to 10 mg Cr(VI)/L. Furthermore, these aerosol measurements may be relevant to estimating airborne exposures to other nonvolatile chemicals.

Adolescent↗