Measured removal rates of chrysotile asbestos fibers from air and comparison with theoretical estimates based on gravitational settling and dilution ventilation.

CONTEXT: Industrial hygiene assessments often focus on activity-based airborne asbestos concentration measurements, but few empirical data exist regarding the fiber removal rate from air after activities cease. OBJECTIVE: Grade 7T chrysotile indoor fiber settling (FS) rates were characterized using air sampling (NIOSH Method 7402). MATERIALS AND METHODS: Six replicate events were conducted in a 58 m(3) study chamber (ventilation 3.5 ACH), in which chrysotile-contaminated work clothing was manipulated for 15 min followed by 30 min of no activity. The fiber concentration decay constant and removal rate were characterized using an exponential decay model based on the measurements. RESULTS: Breathing zone airborne chrysotile concentrations decreased by 86% within 15-30 min after fiber disturbance, compared to concentrations during active disturbance (p < 0.05). Estimated mean time required for 99% of the phase contrast microscopy-equivalent (PCME) fibers to be removed from air was approximately 30 min (95% CI: 22-57 min). The observed effective FS velocity was 0.0034 m/s. This settling velocity was between 4.5-fold and 180-fold faster than predicted by two different particulate gravitational settling models. Additionally, PCME concentrations decreased approximately 2.5-fold faster than predicted due to air exchange alone (32 versus 79 min to 99% decrease in concentration). DISCUSSION: Other measurement studies have reported similar airborne fiber removal rates, supporting the finding that factors other than gravitational settling and dilution ventilation contribute measurably to PCM fiber removal from air (e.g. impaction, agglomeration). CONCLUSION: Overall, the scientific weight of evidence indicates that the time necessary for removal of 99% of fibers greater than 5 µm in length (with aspect ratios greater than 3:1) is approximately 20-80 min.

Evaluation of take-home exposure and risk associated with the handling of clothing contaminated with chrysotile asbestos.

The potential for para-occupational (or take-home) exposures from contaminated clothing has been recognized for the past 60 years. To better characterize the take-home asbestos exposure pathway, a study was performed to measure the relationship between airborne chrysotile concentrations in the workplace, the contamination of work clothing, and take-home exposures and risks. The study included air sampling during two activities: (1) contamination of work clothing by airborne chrysotile (i.e., loading the clothing), and (2) handling and shaking out of the clothes. The clothes were contaminated at three different target airborne chrysotile concentrations (0-0.1 fibers per cubic centimeter [f/cc], 1-2 f/cc, and 2-4 f/cc; two events each for 31-43 minutes; six events total). Arithmetic mean concentrations for the three target loading levels were 0.01 f/cc, 1.65 f/cc, and 2.84 f/cc (National Institute of Occupational Health and Safety [NIOSH] 7402). Following the loading events, six matched 30-minute clothes-handling and shake-out events were conducted, each including 15 minutes of active handling (15-minute means; 0.014-0.097 f/cc) and 15 additional minutes of no handling (30-minute means; 0.006-0.063 f/cc). Percentages of personal clothes-handling TWAs relative to clothes-loading TWAs were calculated for event pairs to characterize exposure potential during daily versus weekly clothes-handling activity. Airborne concentrations for the clothes handler were 0.2-1.4% (eight-hour TWA or daily ratio) and 0.03-0.27% (40-hour TWA or weekly ratio) of loading TWAs. Cumulative chrysotile doses for clothes handling at airborne concentrations tested were estimated to be consistent with lifetime cumulative chrysotile doses associated with ambient air exposure (range for take-home or ambient doses: 0.00044-0.105 f/cc year).

Risk characterization of N-nitrosodimethylamine in pharmaceuticals.

Since 2018, N-nitrosodimethylamine (NDMA) has been a reported contaminant in numerous pharmaceutical products. To guide the pharmaceutical industry, FDA identified an acceptable intake (AI) of 96 ng/day NDMA. The approach assumed a linear extrapolation from the Carcinogenic Potency Database (CPDB) harmonic-mean TD50 identified in chronic studies in rats. Although NDMA has been thought to act as a mutagenic carcinogen in experimental animals, it has not been classified as a known human carcinogen by any regulatory agency. Humans are exposed to high daily exogenous and endogenous doses of NDMA. Due to the likelihood of a threshold dose for NDMA-related tumors in animals, we believe that there is ample scientific basis to utilize the threshold-based benchmark dose or point-of-departure (POD) approach when estimating a Permissible Daily Exposure limit (PDE) for NDMA. We estimated that 29,000 ng/kg/day was an appropriate POD for calculating a PDE. Assuming an average bodyweight of 50 kg, we expect that human exposures to NDMA at doses below 5800 ng/day in pharmaceuticals would not result in an increased risk of liver cancer, and that there is little, if any, risk for any other type of cancer, when accounting for the mode-of-action in humans.

Airborne asbestos concentrations associated with heavy equipment brake removal.

Asbestos-containing brake linings were used in heavy-duty construction equipment such as tractors, backhoes, and bulldozers prior to the 1980s. While several published studies have evaluated exposures to mechanics during brake repair work, most have focused on automobiles and light trucks, not on heavy agricultural or construction vehicles. The purpose of this study is to characterize the airborne concentration of asbestos to workers and bystanders from brake wear debris during brake removal from 12 loader/backhoes and tractors manufactured between 1960 and 1980. Asbestos content in brake lining (average 20% chrysotile by polarized light microscopy) and brake wear debris [average 0.49% chrysotile by transmission electron microscopy (TEM)] was also quantified. Breathing zone samples on the lapel of mechanics (n = 44) and area samples at bystander (n = 34), remote (n = 22), and ambient (n = 12) locations were collected during 12 brake changes and analyzed using phase contrast microscopy (PCM) [National Institute for Occupational Safety and Health (NIOSH) 7400] and TEM (NIOSH 7402). In addition, the fiber distribution by size and morphology was evaluated according to the International Organization for Standardization method for asbestos. Applying the ratio of asbestos fibers:total fibers (including non-asbestos) as determined by TEM to the PCM results, the average airborne chrysotile concentrations (PCM equivalent) were 0.024 f/cc for the mechanic and 0.009 f/cc for persons standing 1.2-3.1 m from the activity during the period of exposure ( approximately 0.5 to 1 h). Considering the time involved in the activity, and assuming three brake jobs per shift, these results would convert to an average 8-h time-weighted average of 0.009 f/cc for a mechanic and 0.006 f/cc for a bystander. The results indicate that (i) the airborne concentrations for worker and bystander samples were significantly less than the current occupational exposure limit of 0.1 f/cc; (ii) approximately 2% of respirable fibers were >20 microm in length; and (iii) approximately 95% of chrysotile in the brake linings degraded in the friction process. The industrial hygiene data presented here should be useful for conducting retrospective and current exposure assessments of individuals, as well as hazard assessments of work activities that involve repairing and replacing asbestos-containing brakes in heavy construction equipment.

Historical analysis of airborne beryllium concentrations at a copper beryllium machining facility (1964-2000).

Copper beryllium alloys are the most commonly used form of beryllium; however, there have been few studies assessing occupational exposure in facilities that worked exclusively with this alloy versus those where pure metal or beryllium oxide may also have been present. In this paper, we evaluated the airborne beryllium concentrations at a machining plant using historical industrial hygiene samples collected between 1964 and 2000. With the exception of a few projects conducted in the 1960s, it is believed that >95% of the operations used copper beryllium alloy exclusively. Long-term (>120 min) and short-term (<120 min) personal and area samples were collected during a variety of activities including machining of copper beryllium-containing parts, as well as finishing operations (e.g., deburring and polishing) and decontamination of machinery. A total of 580 beryllium air samples were analyzed (311 personal and 269 area samples). The average concentration based on area samples (1964-2000) was 0.021 microg m(-3) (SD 0.17 microg m(-3); range 0.00012-2.5 microg m(-3)); 68.8% were below the analytical limit of detection (LOD). The average airborne beryllium concentration, based on all personal samples available from 1964 through the end of 2000 (n = 311), was 0.026 microg m(-3) (SD 0.059 microg m(-3); range 0.019-0.8 microg m(-3)); 97.4% were below the LOD. Personal samples collected from machinists (n = 78) had an average airborne concentration of 0.021 microg m(-3) (SD 0.014 microg m(-3); range 0.019-0.14 microg m(-3)); 97.4% were below the LOD. Airborne concentrations were consistently below the Occupational Safety and Health Administration permissible exposure limit for beryllium (2 microg m(-3)). Overall, the data indicate that for machining operations involving copper beryllium, the airborne concentrations for >95% of the samples were below the contemporaneous occupational exposure limits or the 1999 Department of Energy action level of 0.2 microg m(-3) and, in most cases, were below the LOD.

Exposure to chrysotile asbestos associated with unpacking and repacking boxes of automobile brake pads and shoes.

Industrial hygiene surveys and epidemiologic studies of auto mechanics have shown that these workers are not at an increased risk of asbestos-related disease; however, concerns continue to be raised regarding asbestos exposure from asbestos-containing brakes. Handling new asbestos-containing brake components has recently been suggested as a potential source of asbestos exposure. A simulation study involving the unpacking and repacking of 105 boxes of brakes (for vehicles ca. 1946-80), including 62 boxes of brake pads and 43 boxes of brake shoes, was conducted to examine how this activity might contribute to both short-term and 8-h time-weighted average exposures to asbestos. Breathing zone samples on the lapel of a volunteer worker (n = 80) and area samples at bystander (e.g., 1.5 m from worker) (n = 56), remote area (n = 26) and ambient (n = 10) locations collected during the unpacking and repacking of boxes of asbestos-containing brakes were analyzed by phase contrast microscopy and transmission electron microscopy. Exposure to airborne asbestos was characterized for a variety of parameters including the number of boxes handled, brake type (i.e. pads versus shoes) and the distance from the activity (i.e. worker, bystander and remote area). This study also evaluated the fiber size and morphology distribution according to the International Organization for Standardization analytical method for asbestos. It was observed that (i) airborne asbestos concentrations increased with the number of boxes unpacked and repacked, (ii) handling boxes of brake pads resulted in higher worker asbestos exposures compared to handling boxes of brake shoes, (iii) cleanup and clothes-handling tasks produced less airborne asbestos than handling boxes of brakes and (iv) fiber size and morphology analysis showed that while the majority of fibers were free (e.g. not associated with a cluster or matrix), <30% were respirable and even fewer were of the size range (>20 microm length) considered to pose the greatest risk of asbestos-related disease. It was found that average airborne chrysotile concentrations (30 min) ranged from 0.086 to 0.368 and 0.021 to 0.126 f cc(-1) for a worker unpacking and repacking 4-20 boxes of brake pads and 4-20 boxes of brake shoes, respectively. Additionally, average airborne asbestos exposures (30 min) at bystander locations ranged from 0.004 to 0.035 and 0.002 to 0.011 f cc(-1) when 4-20 boxes of brake pads and 4-20 boxes of brake shoes were handled, respectively. These data show that a worker handling a relatively large number of boxes of brakes over short periods of time will not be exposed to airborne asbestos in excess of its historical or current short-term occupational exposure limits.

DNA-protein cross-links as a biomarker of Cr(VI) exposure.

Comment on A. Zhitkovich et al. :Utilization of DNA-protein cross-links as a biomarker of chromium exposure. Environ Health Perspect 106(suppl 4):969-974 (1998).

Benzene toxicity and risk assessment, 1972-1992: implications for future regulation.

Acute and chronic exposure to benzene vapors poses a number of health hazards to humans. To evaluate the probability that a specific degree of exposure will produce an adverse effect, risk assessment methods must be used. This paper reviews much of the published information and evaluates the various risk assessments for benzene that have been conducted over the past 20 years. There is sufficient evidence that chronic exposure to relatively high concentrations of benzene can produce an increased incidence of acute myelogenous leukemia (AML). Some studies have indicated that benzene may cause other leukemias, but due to the inconsistency of results, the evidence is not conclusive. To predict the leukemogenic risk for humans exposed to much lower doses of benzene than those observed in most epidemiology studies, a model must be used. Although several models could yield plausible results, to date most risk assessments have used the linear-quadratic or conditional logistic models. These appear to be the most appropriate ones for providing the cancer risk for airborne concentrations of 1 ppb to 10 ppm, the range most often observed in the community and workplace. Of the seven major epidemiology studies that have been conducted, there is a consensus that the Pliofilm cohort (rubber workers) is the best one for estimating the cancer potency because it is the only one with good exposure and incidence of disease data. The current EPA, OSHA, and ACGIH cancer potency estimates for benzene are based largely on this cohort. A retrospective exposure assessment and an analysis of the incidence of disease in these workers were completed in 1991. All of these issues are discussed and the implications evaluated in this paper. The range of benzene exposures to which Americans are commonly exposed and the current regulatory criteria are also presented.

A physiologically based model for the ingestion of chromium(III) and chromium(VI) by humans.

A physiologically based model of human chromium kinetics has been developed, based on an existing physiologically based model of human body and bone growth (O'Flaherty, 1993, Toxicol. Appl. Pharmacol. 118, 16-29; 1995a, Toxicol. Appl. Pharmacol. 131, 297-308; 2000, Toxicol. Sci. 55, 171-18) and an existing physiologically based model of chromium kinetics in rats (O'Flaherty, 1996, Toxicol. Appl. Pharmacol. 138, 54-64). Key features of the adapted model, specific to chromium, include differential absorption of Cr(VI) and Cr(III), rapid reduction of Cr(VI) to Cr(III) in all body fluids and tissues, modest incorporation of chromium into bone, and concentration-dependent urinary clearance consistent with parallel renal processes that conserve chromium efficiently at ambient exposure levels. The model does not include a physiologic lung compartment, but it can be used to estimate an upper limit on pulmonary absorption of inhaled chromium. The model was calibrated against blood and urine chromium concentration data from a group of controlled studies in which adult human volunteers drank solutions generally containing up to 10 mg/day of soluble inorganic salts of either Cr(III) (chromic chloride, CrCl(3)) or Cr(VI) (potassium dichromate, K(2)Cr(2)O(7)) (Finley et al., 1997, Toxicol. Appl. Pharmacol. 142, 151-159; Kerger et al., 1996, Toxicol. Appl. Pharmacol. 141, 145-158; Paustenbach et al., 1996, J. Toxicol. Environ. Health 49, 453-461). In one of the studies, in which the chromium was ingested in orange juice, urinary clearance was observed to be more rapid than when inorganic chromium was ingested. Chromium kinetics were shown not to be dependent on the oxidation state of the administered chromium except in respect to the amount absorbed at these ambient and moderate-to-high exposures. The fraction absorbed from administered Cr(VI) compounds was highly variable and was presumably strongly dependent on the degree of reduction in the gastrointestinal tract, that is, on the amount and nature of the stomach contents at the time of Cr(VI) ingestion. The physiologically based model is applicable to both single-dose oral studies and chronic oral exposure, in that it adequately reproduced the time dependence of blood plasma concentrations and rates of urinary chromium excretion in one of the subjects who, in a separate experiment, ingested daily 4 mg of an inorganic Cr(VI) salt in 5 subdivided doses of 0.8 mg each for a total of 17 days. The high degree of variability of fractional absorption of Cr(VI) from the gastrointestinal tract leads to uncertainty in the assignment of a meaningful value to this parameter as applied to single Cr(VI) doses. To model chronic oral chromium exposure at ambient or moderately above-ambient levels, the physiologically based model in its present form should be usable with urinary clearance set to a constant value of 1-2 liters/day and the gastrointestinal absorption rate constants set at 0.25/day for Cr(III) and 2.5/day for Cr(VI). The model code is given in full in the Appendix.

Proposed occupational exposure limits for select ethylene glycol ethers using PBPK models and Monte Carlo simulations.

Methoxyethanol (ethylene glycol monomethyl ether, EGME), ethoxyethanol (ethylene glycol monoethyl ether, EGEE), and ethoxyethyl acetate (ethylene glycol monoethyl ether acetate, EGEEA) are all developmental toxicants in laboratory animals. Due to the imprecise nature of the exposure data in epidemiology studies of these chemicals, we relied on human and animal pharmacokinetic data, as well as animal toxicity data, to derive 3 occupational exposure limits (OELs). Physiologically based pharmacokinetic (PBPK) models for EGME, EGEE, and EGEEA in pregnant rats and humans have been developed (M. L. Gargas et al., 2000, Toxicol. Appl. Pharmacol. 165, 53-62; M. L. Gargas et al., 2000, Toxicol. Appl. Pharmacol. 165, 63-73). These models were used to calculate estimated human-equivalent no adverse effect levels (NAELs), based upon internal concentrations in rats exposed to no observed effect levels (NOELs) for developmental toxicity. Estimated NAEL values of 25 ppm for EGEEA and EGEE and 12 ppm for EGME were derived using average values for physiological, thermodynamic, and metabolic parameters in the PBPK model. The uncertainties in the point estimates for the NOELs and NAELs were estimated from the distribution of internal dose estimates obtained by varying key parameter values over expected ranges and probability distributions. Key parameters were identified through sensitivity analysis. Distributions of the values of these parameters were sampled using Monte Carlo techniques and appropriate dose metrics calculated for 1600 parameter sets. The 95th percentile values were used to calculate interindividual pharmacokinetic uncertainty factors (UFs) to account for variability among humans (UF(h,pk)). These values of 1.8 for EGEEA/EGEE and 1.7 for EGME are less than the default value of 3 for this area of uncertainty. The estimated human equivalent NAELs were divided by UF(h,pk) and the default UFs for pharmacodynamic variability among animals and among humans to calculate the proposed OELs. This methodology indicates that OELs (8-h time-weighted average) that should protect workers from the most sensitive adverse effects of these chemicals are 2 ppm EGEEA and EGEE (11 mg/m(3) EGEEA, 7 mg/m(3) EGEE) and 0.9 ppm (3 mg/m(3)) EGME. These recommendations assume that dermal exposure will be minimal or nonexistent.

Physiologically based pharmacokinetic and pharmacodynamic modeling in health risk assessment and characterization of hazardous substances.

Recent advances in physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) modeling have introduced novel approaches for evaluating toxicological problems. Because PBPK models are amenable to extrapolation of tissue dosimetry, they are increasingly being applied to chemical risk assessment. A comprehensive listing of PBPK/PD models for environmental chemicals developed to date is referenced. Salient applications of PBPK/PD modeling to health risk assessments and characterization of hazardous substances are illustrated with examples.

Cancer risk assessment for dioxane based upon a physiologically-based pharmacokinetic approach.

A cancer bioassay conducted in 1974 (Kociba et al.) indicated that rats given drinking water containing dioxane at a dose of 1184 mg.kg-1.d-1 produced an increased incidence of liver tumors. Applying the linearized multistage extrapolation model to these data, the administered dose estimated to present a human cancer risk of 1 in 100,000 (10(-5)) was 0.01 mg.kg-1.d-1. As in customary regulatory policy, this estimate assumed that humans were about 5.5 times more sensitive than rats on a mg/kg basis. However, this approach did not consider that the metabolism of dioxane is saturable at high doses. Based on experience with similar chemicals, it is known that the conventional risk extrapolation method may overestimate the most likely human cancer risk. In order to determine more accurately the likely human response following lifetime exposure to dioxane, a physiologically-based pharmacokinetic (PB-PK) model was developed. The objective of this study was to establish a quantitative relationship between the administered dose of dioxane and the internal dose delivered to the target organ. Using this PB-PK model, and assuming that the best dose surrogate for estimating the liver tumor response was the time-weighted average lifetime liver dioxane concentration, the cancer risk for humans exposed to low doses of dioxane was estimated. The dose surrogate in humans most likely to be associated with a tumorigenic response of 1 in 100,000 is 280 mumol/l, equivalent to an administered dose of about 59 mg.kg-1.d-1. The 95% lower confidence limit on the dose surrogate at the same response level is 1.28 mumol/l, equivalent to an administered dose of 0.8 mg.kg-1.d-1. This PB-PK analysis indicated that conventional approaches based on the administered doses in the rodent bioassay, if uncorrected for metabolic and physiological differences between rats and humans, will overestimate the human cancer risk of dioxane by as much as 80-fold.

Toxicological evaluation of substituted dicyclopentadienyliron (ferrocene) compounds.

The acute toxicity of 3 substituted ferrocenes: acetylferrocene, ethylferrocene, and 2,2-bis(ethylferrocenyl)propane (Catocene) were studied in rats, rabbits and monkeys. Acetylferrocene was found to be the most toxic. The oral lethal dose was less than 5 mg/kg for female rats, between 5 and 50 mg/kg for male rats, and between 10 and 100 mg/kg for monkeys. The toxicity of acetylferrocene appeared to be delayed, with most mortality occurring on the third day after dosing. Acetylferrocene was also highly toxic by skin or eye exposure. Gross pathological examination revealed signs of pneumonopathy in both the rats and monkeys. The mechanism by which monkeys are less susceptible than rats to the toxicity of acetylferrocene is not clear.

A physiologically based pharmacokinetic model for 2,3,7,8-tetrachlorodibenzo-p-dioxin in C57BL/6J and DBA/2J mice.

A five-compartment physiologically based pharmacokinetic (PB-PK) model was developed to describe the time course of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the tissues of both C57BL/6J and DBA/2J mice. The PB-PK model included binding in blood and two hepatic binding sites, one in the cytosol and the other in the microsomes. First-order metabolism occurred in the liver. Model simulations were compared to literature results for the disposition of a single intraperitoneal dose of 10 micrograms/kg of [3H]TCDD, reported by Gasiewicz et al. [Drug Metab. Dispos. 11 (1983) 397-403]. In contrast to previous speculation, the greater accumulation of TCDD in the liver of the C57BL/6J mouse, as compared to the DBA/2J mouse, was not attributable to the higher fat content in the DBA/2J mouse. Instead, the disposition of TCDD in these mice was more dependent on the affinity of the microsomal binding proteins than on fat content. The microsomal dissociation constant in the C57BL/6J mouse estimated by the PB-PK model was about one-third its value in the DBA/2J mouse (20 versus 75 nM), i.e. there is more avid microsomal binding in the liver of the C57BL/6J mouse. In the concentration range covered in these time-course studies, the cytosolic receptor, with its low capacity and very high affinity binding characteristics, does not play a major role in determining the overall tissue distribution pattern. The concentration and affinity of the microsomal binding protein in the liver appear to be primarily responsible for explaining the differences in the liver/fat concentration ratios between various strains and species of laboratory animals.

Relative distribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin in human hepatic and adipose tissues.

Paired human hepatic and adipose tissues from 26 people were assayed for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). On a whole tissue weight basis, TCDD concentration in the liver was about one-tenth that in the adipose tissue. When expressed in total tissue lipid basis, the TCDD concentrations in the liver and adipose tissue were about equal. At low levels of exposure, presumably below those necessary to cause hepatic enzyme induction, TCDD appeared to be partitioning into the human liver predominantly on the basis of its lipid solubility in that tissue store. The partitioning behavior of TCDD in the livers of humans exposed to higher levels of TCDD is currently unclear.

PCB and dioxin re-entry criteria for building surfaces and air.

A number of fires involving polychlorinated biphenyl (PCB)-containing transformers and capacitors have occurred in the United States. PCB fires generate by-products such as polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzodioxins (PCDDs) and, when the transformer is in a building, contaminate the interior. Considerable concern exists over the potential human health effects associated with exposure by inhabitants to residual levels of PCBs, PCDFs and PCDDs. Office workers, for example, may be exposed to these chlorinated compounds via inhalation of contaminated particulates and vapors, dermal contact with contaminated surfaces, and incidental ingestion of dusts. A wide range of re-entry or cleanup levels have been developed for PCDDs and PCBs to protect workers who re-occupy a building following a PCB fire. Re-entry criteria have been used by property owners and regulatory agencies to determine whether the building is safe to re-occupy or to determine the extent of needed remediation. This paper presents a mass balance approach to deriving risk-based re-entry surface and air criteria for PCBs and PCDD/PCDFs. These criteria were based on a lifetime risk level of 10(-5), recent toxicological data on PCDDs and PCBs, and plausible exposure scenarios. Our analysis suggests that 125 ng/m2 2,3,7,8-TCDD TEQ for surfaces and 10 pg/m3 for air are acceptable. Based on Aroclor 1260, risk-based re-entry criteria for PCBs on surfaces and in air were 750 micrograms/m2 and 0.1 microgram/m3, respectively. In comparison to most previous guidelines, these risk-based criteria are less stringent, but can still be considered conservative. The surface criteria are 5 to up to 125 fold higher than previous guidelines. Air criteria range up to 5 times higher than criteria used at past PCB fire sites. Air concentrations associated with these were modeled and were negligible. For PCBs in air, the NIOSH guideline of 1 microgram/m3 is also appropriate for occupational settings.

Systemic uptake of chromium in human volunteers following dermal contact with hexavalent chromium (22 mg/L).

This study examined the systemic uptake of chromium in four human volunteers following three hours of contact with water containing hexavalent chromium [Cr(VI)] at a concentration of 22 mg/L. Volunteers were immersed below the shoulders in water at 91 +/- 2.5 degrees F. On the day prior to the experiment and for five days afterwards, samples of urine, plasma, and red blood cells (RBCs) were collected and analyzed for total chromium. Red blood cell chromium concentrations were used as a specific biomarker for systemic uptake of Cr(VI). Although total chromium concentrations in RBCs and plasma increased relative to historical background concentrations on the day of exposure, no sustained elevation of chromium concentrations was observed in RBCs or plasma of the volunteers tested. Since absorption of chromium in the hexavalent state would result in the irreversible binding of Cr(VI) to hemoglobin within the RBC (manifested as a sustained elevation of total chromium concentrations in the RBC), the pattern of blood uptake and urinary excretion observed was consistent with uptake and distribution of chromium in the trivalent state. Small increases were observed in the concentration of total chromium in urine within 48 h of exposure, indicating that some trivalent chromium [Cr(III)] may have penetrated the skin at a rate of about 3.3 x 10(-5) to 4.1 x 10(-4) micrograms/ cm2-h. In short, the data indicated that a 3-h contact with Cr(VI) at concentrations in water plausible for environmental exposure (e.g., swimming) was not expected to result in systemic uptake of measurable amounts of Cr(VI), although a small quantity of Cr(VI) may have penetrated the skin where it was subsequently reduced to Cr(III) prior to systemic uptake.

The effect of cooking practices on the concentration of DDT and PCB compounds in the edible tissue of fish.

Chemical contaminants in fish can be an important source of human exposure to chemicals. Assessments of the fish consumption pathway need to adjust the concentrations of the chemical to account for reductions in 1,1-bis(4-chlorophenyl)-2,2-dichloroethane (DDD), dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyltrichloroethane (DDT) (herein collectively referred to as total DDT or tDDT) and polychlorinated biphenyls (PCBs) that can occur during cooking. The results of this analysis indicate that baking, frying, broiling, boiling, smoking, and microwaving all effectively reduce the concentrations of tDDT and PCBs in fish tissue. Average reductions in tDDT ranged from 16 to 55% depending on the cooking method. Similar reductions in PCBs ranged from 26 to 68%. An evaluation of the factors influencing the degree of cooking loss indicated that neither initial chemical mass in the raw fillet, fillet lipid content, nor skin removal were significant predictors of the percent reduction in tDDT or PCB.

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.