Routes of Chloroform Exposure and Body Burden from Showering with Chlorinated Tap Water

While there is an awareness of the need to quantify inhalation exposure from showers, the potential for dermal exposure to organic contaminants in showers has not been appreciated or explored. To establish routes of environmental exposure from showers, comparisons of the concentration of chloroform in exhaled breath after a normal shower with municipal tap water were made with those after an inhalation-only exposure. The postexposure chloroform breath concentrations ranged from 6.0-21 micrograms/m3 for normal showers and 2.4 to 10 micrograms/m3 for inhalation-only exposure, while the pre-exposure concentrations were all less than the minimum detection limit of 0.86 micrograms/m3. According to an F-test, the difference between the normal shower and the inhalation-only exposures was considered significant at a probability of p = 0.0001. Based on the difference, the mean internal dose due to dermal exposure was found to be approximately equal to that due to the inhalation exposure. The effect of the showering activities on the concentration of chloroform shower air was examined by comparing air concentrations during a normal shower with the air concentrations obtained when the shower was unoccupied. The F-test showed that there is no significant difference between the two sets of data.     

A Compartmental Model for the Prediction of Breath Concentration and Absorbed Dose of Chloroform After Exposure While Showering

In order to predict the exhaled breath concentration of chloroform in individuals exposed to chloroform while showering, an existing physiologically based pharmacokinetic (PB-PK) model was modified to include a multicompartment, PB-PK model for the skin and a completely mixed shower exposure model. The PB-PK model of the skin included the stratum corneum as the principal resistance to absorption and a viable epidermis which is in dynamic equilibrium with the skin microcirculation. This model was calibrated with measured exhaled breath concentrations of chloroform in individuals exposed while showering with and without dermal absorption. The calibration effort indicated that the expected value of skin-blood partitioning coefficient would be 1.2 when the degree of transfer of chloroform from shower water into shower air was 61%. The stratum corneum permeability coefficient for chloroform was estimated to be within the range of 0.16-0.36 cm/hr and the expected value was 0.2 cm/hr. The estimated ratio of the dermally and inhaled absorbed doses ranged between 0.6 and 2.2 and the expected value was 0.75. These results indicate that for the purposes of risk assessment for dermal exposure to chloroform, a simple steady-state model can be used to predict the degree of dermal absorption and that a reasonable value of skin permeability coefficient for chloroform used in this model would be 0.2 cm/hr. Further research should be conducted to compare the elimination of chloroform via exhaled breath when different exposure routes are being compared. The model results from this study suggest that multiple measurements of exhaled breath concentrations after exposure may be necessary when making comparisons of breath concentrations that involve different exposure routes.     

Exposure to Chlorination By-Products from Hot Water Uses

Exposures to chlorination by-products (CBP) within public water supplies are multiroute in water. Cold water is primarily used for ingestion while a mixture of cold water and hot water is used for showering, bathing others, dish washing, etc. These latter two activities result in inhalation and dermal exposure. Heating water was observed to change the concentration of various CBP. An increase in the trihalomethanes (THM) concentrations and a decrease in the haloacetonitriles and halopropanones concentration, though an initial rise in the concentration of dichloropropanone, were observed. The extent of the increase in the THM is dependent on the chlorine residual present. Therefore, estimates of total exposure to CBP from public water supplies need to consider any changes in their concentration with different water uses. The overall THM exposures calculated using the THM concentration in heated water were 50% higher than those calculated using the THM concentration present in cold water. The estimated lifetime cancer risk associated with exposure to THM in water during the shower is therefore underestimated by 50% if the concentration of THM in cold water is used in the risk assessment.     

An Analysis of the Uncertainties in Estimates of Radon-Induced Lung Cancer

A recent report by the National Academy of Sciences estimates that the radiation dose to the bronchial epithelium, per working level month (WLM) of radon daughter exposure, is about 30% lower for residential exposures than for exposures received in underground mines. Adjusting the previously published BEIR IV radon risk model accordingly, the unit risk for indoor exposures of the general population is about 2.2 x 10(-4) lung cancer deaths (lcd)/WLM. Using results from EPA's National Residential Radon Survey, the average radon level is estimated to be about 1.25 pCi/L, and the annual average exposure about 0.242 WLM. Based on these estimates, 13,600 radon-induced lcd/yr are projected for the United States. A quantitative uncertainty analysis was performed, which considers: statistical uncertainties in the epidemiological studies of radon-exposed miners; the dependence of risk on age at, and time since, exposure; the extrapolation of risk estimates from mines to homes based on comparative dosimetry; and uncertainties in the radon daughter levels in homes and in the average residential occupancy. Based on this assessment of the uncertainties in the unit risk and exposure estimates, an uncertainty range of 7000-30000 lcd/yr is derived.     

A Physiologically-Based Pharmacokinetic Model Assessment of Methyl t-Butyl Ether in Groundwater for a Bathing and Showering Determination

Methyl t -butyl ether (MTBE) is a gasoline additive that has appeared in private wells as a result of leaking underground storage tanks. Neurological symptoms (headache, dizziness) have been reported from household use of MTBE-affected water, consistent with animal studies showing acute CNS depression from MTBE exposure. The current research evaluates acute CNS effects during bathing/showering by application of physiologically-based pharmacokinetic (PBPK) techniques to compare internal doses in animal toxicity studies to human exposure scenarios. An additional reference point was the delivered dose associated with the acute Minimum Risk Level (MRL) for MTBE established by the Agency for Toxic Substances and Disease Registry. A PBPK model for MTBE and its principal metabolite, t -butyl alcohol (TBA) was developed and validated against published data in rats and humans. PBPK analysis of animal studies showed that acute CNS toxicity after MTBE exposure can be attributed principally to the parent compound since the metabolite (TBA) internal dose was below that needed for CNS effects. The PBPK model was combined with an exposure model for bathing and showering which integrates inhalation and dermal exposures. This modeling indicated that bathing or showering in water containing MTBE at 1 mg/L would produce brain concentrations ˜1000-fold below the animal effects level and twofold below brain concentrations associated with the acute MRL. These findings indicate that MTBE water concentrations of 1 mg/L or below are unlikely to trigger acute CNS effects during bathing and showering. However, MTBE's strong odor may be a secondary but deciding factor regarding the suitability of such water for domestic uses.     

A Physiologically Based Pharmacokinetic Assessment of Tetrachloroethylene in Groundwater for a Bathing and Showering Determination

A two-step methodology is described to make a health-based determination for the bathing and showering use of the water from a private well contaminated with volatile organic chemicals. The chemical perchloroethylene (PERC) is utilized to illustrate the approach. First, a chemical-specific exposure model is used to predict the concentration of PERC in the shower air, shower water, and in the air above the bathtub. Second, a physiologically based pharmacokinetic (PBPK) model is used to predict the concentration of PERC delivered to the target tissue, the brain, since the focus is on neurological endpoints. The simulation exercise includes concurrent dermal and inhalation routes of exposure. A reference target tissue level (RTTL) in the brain is estimated using the PBPK model. A hazard index based on this benchmark guideline is used to make a regulatory determination for bathing and showering use of the contaminated water.     

Dose-Response and Risk Assessment of Airborne Hexavalent Chromium and Lung Cancer Mortality

This study evaluates the dose-response relationship for inhalation exposure to hexavalent chromium [Cr(VI)] and lung cancer mortality for workers of a chromate production facility, and provides estimates of the carcinogenic potency. The data were analyzed using relative risk and additive risk dose-response models implemented with both Poisson and Cox regression. Potential confounding by birth cohort and smoking prevalence were also assessed. Lifetime cumulative exposure and highest monthly exposure were the dose metrics evaluated. The estimated lifetime additional risk of lung cancer mortality associated with 45 years of occupational exposure to 1 microg/m3 Cr(VI) (occupational exposure unit risk) was 0.00205 (90%CI: 0.00134, 0.00291) for the relative risk model and 0.00216 (90%CI: 0.00143, 0.00302) for the additive risk model assuming a linear dose response for cumulative exposure with a five-year lag. Extrapolating these findings to a continuous (e.g., environmental) exposure scenario yielded an environmental unit risk of 0.00978 (90%CI: 0.00640, 0.0138) for the relative risk model [e.g., a cancer slope factor of 34 (mg/kg-day)-1] and 0.0125 (90%CI: 0.00833, 0.0175) for the additive risk model. The relative risk model is preferred because it is more consistent with the expected trend for lung cancer risk with age. Based on statistical tests for exposure-related trend, there was no statistically significant increased lung cancer risk below lifetime cumulative occupational exposures of 1.0 mg-yr/m3, and no excess risk for workers whose highest average monthly exposure did not exceed the current Permissible Exposure Limit (52 microg/m3). It is acknowledged that this study had limited power to detect increases at these low exposure levels. These cancer potency estimates are comparable to those developed by U.S. regulatory agencies and should be useful for assessing the potential cancer hazard associated with inhaled Cr(VI).     

Multi-Stage Model Estimates of Lung Cancer Risk from Exposure to Diesel Exhaust, Based on a U.S. Railroad Worker Cohort

A California Environmental Protection Agency (Cal/EPA) report concluded that a reasonable and likely explanation for the increased lung cancer rates in numerous epidemiological studies is a causal association between diesel exhaust exposure and lung cancer. A version of the present analysis, based on a retrospective study of a U.S. railroad worker cohort, provided the Cal/EPA report with some of its estimates of lung cancer risk associated with diesel exhaust. The individual data for that cohort study furnish information on age, employment, and mortality for 56,000 workers over 22 years. Related studies provide information on exposure concentrations. Other analyses of the original cohort data reported finding no relation between measures of diesel exhaust and lung cancer mortality, while a Health Effects Institute report found the data unsuitable for quantitative risk assessment. None of those three works used multistage models, which this article uses in finding a likely quantitative, positive relations between lung cancer and diesel exhaust. A seven-stage model that has the last or next-to-last stage sensitive to diesel exhaust provides best estimates of increase in annual mortality rate due to each unit of concentration, for bracketing assumptions on exposure. Using relative increases of risk and multiplying by the background lung cancer mortality rates for California, the 95% upper confidence limit of the 70-year unit risks for lung cancer is estimated to be in the range 2.1 x 10(-4) (microg/m3)(-1) to 5.5 x 10(-4) (microg/m3)(-1). These risks constitute the low end of those in the Cal/EPA report and are below those reported by previous investigators whose estimates were positive using human data.     

A dose-response analysis of skin cancer from inorganic arsenic in drinking water

A study of the prevalence of skin cancer among 40,421 persons consuming arsenic-contaminated drinking water in Taiwan was used for a cancer dose-response assessment of ingested arsenic. The numbers of persons at risk over three dose intervals and four exposure durations were estimated from the data in order to apply the method of maximum likelihood to a multistage-Weibull time/dose-response model. A constant exposure level since birth for each of the exposure categories was assumed. It was found that the cumulative hazard increases as a power of three in age, and is linear or quadratic (with a linear coefficient) in dose. Observations from a smaller epidemiologic survey in Mexico were similar to what would be predicted from the model of the Taiwan data. Assuming that the skin cancer risk from ingested arsenic in the American population would also be similar to the Taiwan population, an American male would have a lifetime risk of developing skin cancer of 1.3 x 10(-3) (3.0 x 10(-3] if exposed to 1 microgram/kg/day for a 76-year lifespan (median lifespan in the U.S.).     

Addressing Nonlinearity in the Exposure-Response Relationship for a Genotoxic Carcinogen: Cancer Potency Estimates for Ethylene Oxide

Ethylene oxide (EO) has been identified as a carcinogen in laboratory animals. Although the precise mechanism of action is not known, tumors in animals exposed to EO are presumed to result from its genotoxicity. The overall weight of evidence for carcinogenicity from a large body of epidemiological data in the published literature remains limited. There is some evidence for an association between EO exposure and lympho/hematopoietic cancer mortality. Of these cancers, the evidence provided by two large cohorts with the longest follow-up is most consistent for leukemia. Together with what is known about human leukemia and EO at the molecular level, there is a body of evidence that supports a plausible mode of action for EO as a potential leukemogen. Based on a consideration of the mode of action, the events leading from EO exposure to the development of leukemia (and therefore risk) are expected to be proportional to the square of the dose. In support of this hypothesis, a quadratic dose-response model provided the best overall fit to the epidemiology data in the range of observation. Cancer dose-response assessments based on human and animal data are presented using three different assumptions for extrapolating to low doses: (1) risk is linearly proportionate to dose; (2) there is no appreciable risk at low doses (margin-of-exposure or reference dose approach); and (3) risk below the point of departure continues to be proportionate to the square of the dose. The weight of evidence for EO supports the use of a nonlinear assessment. Therefore, exposures to concentrations below 37 microg/m3 are not likely to pose an appreciable risk of leukemia in human populations. However, if quantitative estimates of risk at low doses are desired and the mode of action for EO is considered, these risks are best quantified using the quadratic estimates of cancer potency, which are approximately 3.2- to 32-fold lower, using alternative points of departure, than the linear estimates of cancer potency for EO. An approach is described for linking the selection of an appropriate point of departure to the confidence in the proposed mode of action. Despite high confidence in the proposed mode of action, a small linear component for the dose-response relationship at low concentrations cannot be ruled out conclusively. Accordingly, a unit risk value of 4.5 x 10(-8) (microg/m3)(-1) was derived for EO, with a range of unit risk values of 1.4 x 10(-8) to 1.4 x 10(-7) (microg/m3)(-1) reflecting the uncertainty associated with a theoretical linear term at low concentrations.     

A Quantitative Risk Assessment of Waterborne Cryptosporidiosis in France Using Second-Order Monte Carlo Simulation

A pragmatic quantitative risk assessment (QRA) of the risks of waterborne Cryptosporidium parvum infection and cryptosporidiosis in immunocompetent and immunodeficient French populations is proposed. The model takes into account French specificities such as the French technique for oocyst enumeration performance and tap water consumption. The proportion of infective oocysts is based on literature review and expert knowledge. The probability of infection for a given number of ingested viable oocysts is modeled using the exponential dose-response model applied on published data from experimental infections in immunocompetent human volunteers challenged with the IOWA strain. Second-order Monte Carlo simulations are used to characterize the uncertainty and variability of the risk estimates. Daily risk of infection and illness for the immunocompetent and the immunodeficient populations are estimated according to the number of oocysts observed in a single storage reservoir water sample. As an example, the mean daily risk of infection in the immunocompetent population is estimated to be 1.08 x 10(-4) (95% confidence interval: [0.20 x 10(-4); 6.83 x 10(-4)]) when five oocysts are observed in a 100 L storage reservoir water sample. Annual risks of infection and disease are estimated from a set of oocyst enumeration results from distributed water samples, assuming a negative binomial distribution of day-to-day contamination variation. The model and various assumptions used in the model are fully explained and discussed. While caveats of this model are well recognized, this pragmatic QRA could represent a useful tool for the French Food Safety Agency (AFSSA) to define recommendations in case of water resource contamination by C. parvum whose infectivity is comparable to the IOWA strain.     

Estimates of Lifetime-Absorbed Daily Doses from the Use of Personal-Care Products Containing Polyacrylamide: A Monte Carlo Analysis

Estimates of the lifetime-absorbed daily dose (LADD) of acrylamide resulting from use of representative personal-care products containing polyacrylamides have been developed. All of the parameters that determine the amount of acrylamide absorbed by an individual vary from one individual to another. Moreover, for some parameters there is uncertainty as to which is the correct or representative value from a range of values. Consequently, the parameters used in the estimation of the LADD of acrylamide from usage of a particular product type (e.g., deodorant, makeup, etc.) were represented by distributions evaluated using Monte Carlo analyses.((1-4)) From these data, distributions of values for key parameters, such as the amount of acrylamide in polyacrylamide, absorption fraction, etc., were defined and used to provide a distribution of LADDs for each personal-care product. The estimated total acrylamide LADD (across all products) for males and females at the median, mean, and 95th percentile of the distribution of individual LADD values were 4.7 x 10(-8), 2.3 x 10(-7), and 7.3 x 10(-7) mg/kg/day for females and 3.6 x 10(-8), 1.7 x 10(-7), and 5.4 x 10(-7) mg/kg/day for males. The ratio of the LADDs to risk-specific dose corresponding to a target risk level of 1 x 10(-5), the acceptable risk level for this investigation, derived using approaches typically used by the FDA, the USEPA, and proposed for use by the European Union (EU) were also calculated. All ratios were well below 1, indicating that all the extra lifetime cancer risk from the use of polyacrylamide-containing personal-care products, in the manner assumed in this assessment, are well below acceptable levels. Even if it were assumed that an individual used all of the products together, the estimated LADD would still provide a dose that was well below the acceptable risk levels.     

A Distributed Parameter Physiologically-Based Pharmacokinetic Model for Dermal and Inhalation Exposure to Volatile Organic Compounds

Estimates of dermal dose from exposures to toxic chemicals are typically derived using models that assume instantaneous establishment of steady-state dermal mass flux. However, dermal absorption theory indicates that this assumption is invalid for short-term exposures to volatile organic chemicals (VOCs). A generalized distributed parameter physiologically-based pharmacokinetic model (DP-PBPK), which describes unsteady state dermal mass flux via a partial differential equation (Fickian diffusion), has been developed for inhalation and dermal absorption of VOCs. In the present study, the DP-PBPK model has been parameterized for chloroform, and compared with two simpler PBPK models of chloroform. The latter are lumped parameter models, employing ordinary differential equations, that do not account for the dermal absorption time lag associated with the accumulation of permeant chemical in tissue represented by permeability coefficients. All three models were evaluated by comparing simulated post-exposure exhaled breath concentration profiles with measured concentrations following environmental chloroform exposures. The DP-PBPK model predicted a time-lag in the exhaled breath concentration profile, consistent with the experimental data. The DP-PBPK model also predicted significant volatilization of chloroform, for a simulated dermal exposure scenario. The end-exposure dermal dose predicted by the DP-PBPK model is similar to that predicted by the EPA recommended method for short-term exposures, and is significantly greater than the end-exposure dose predicted by the lumped parameter models. However, the net dermal dose predicted by the DP-PBPK model is substantially less than that predicted by the EPA method, due to the post-exposure volatilization predicted by the DP-PBPK model. Moreover, the net dermal dose of chloroform predicted by all three models was nearly the same, even though the lumped parameter models did not predict substantial volatilization.     

Potential Airborne Asbestos Exposure and Risk Associated with the Historical Use of Cosmetic Talcum Powder Products

Over time, concerns have been raised regarding the potential for human exposure and risk from asbestos in cosmetic‐talc–containing consumer products. In 1985, the U.S. Food and Drug Administration (FDA) conducted a risk assessment evaluating the potential inhalation asbestos exposure associated with the cosmetic talc consumer use scenario of powdering an infant during diapering, and found that risks were below levels associated with background asbestos exposures and risk. However, given the scope and age of the FDA's assessment, it was unknown whether the agency's conclusions remained relevant to current risk assessment practices, talc application scenarios, and exposure data. This analysis updates the previous FDA assessment by incorporating the current published exposure literature associated with consumer use of talcum powder and using the current U.S. Environmental Protection Agency's (EPA) nonoccupational asbestos risk assessment approach to estimate potential cumulative asbestos exposure and risk for four use scenarios: (1) infant exposure during diapering; (2) adult exposure from infant diapering; (3) adult exposure from face powdering; and (4) adult exposure from body powdering. The estimated range of cumulative asbestos exposure potential for all scenarios (assuming an asbestos content of 0.1%) ranged from 0.0000021 to 0.0096 f/cc‐yr and resulted in risk estimates that were within or below EPA's acceptable target risk levels. Consistent with the original FDA findings, exposure and corresponding health risk in this range were orders of magnitude below upper‐bound estimates of cumulative asbestos exposure and risk at ambient levels, which have not been associated with increased incidence of asbestos‐related disease.     

Quantitative Cancer Risk Estimation for Formaldehyde

Of primary concern are irreversible effects, such as cancer induction, that formaldehyde exposure could have on human health. Dose-response data from human exposure situations would provide the most solid foundation for risk assessment, avoiding problematic extrapolations from the health effects seen in nonhuman species. However, epidemiologic studies of human formaldehyde exposure have provided little definitive information regarding dose-response. Reliance must consequently be placed on laboratory animal evidence. An impressive array of data points to significantly nonlinear relationships between rodent tumor incidence and administered dose, and between target tissue dose and administered dose (the latter for both rodents and Rhesus monkeys) following exposure to formaldehyde by inhalation. Disproportionately less formaldehyde binds covalently to the DNA of nasal respiratory epithelium at low than at high airborne concentrations. Use of this internal measure of delivered dose in analyses of rodent bioassay nasal tumor response yields multistage model estimates of low-dose risk, both point and upper bound, that are lower than equivalent estimates based upon airborne formaldehyde concentration. In addition, risk estimates obtained for Rhesus monkeys appear at least 10-fold lower than corresponding estimates for identically exposed Fischer-344 rats.     

Stochastic Estimates of Exposure and Cancer Risk from Carbon Tetrachloride Released to the Air from the Rocky Flats Plant

Carbon tetrachloride is a degreasing agent that was used at the Rocky Flats Plant (RFP) in Colorado to clean product components and equipment. The chemical is considered a volatile organic compound and a probable human carcinogen. During the time the plant operated (1953-1989), most of the carbon tetrachloride was released to the atmosphere through building exhaust ducts. A smaller amount was released to the air via evaporation from open-air burn pits and ground-surface discharge points. Airborne releases from the plant were conservatively estimated to be equivalent to the amount of carbon tetrachloride consumed annually by the plant, which was estimated to be between 3.6 and 180 Mg per year. This assumption was supported by calculations that showed that most of the carbon tetrachloride discharged to the ground surface would subsequently be released to the atmosphere. Atmospheric transport of carbon tetrachloride from the plant to the surrounding community was estimated using a Gaussian Puff dispersion model (RATCHET). Time-integrated concentrations were estimated for nine hypothetical but realistic exposure scenarios that considered variation in lifestyle, location, age, and gender. Uncertainty distributions were developed for cancer slope factors and atmospheric dispersion factors. These uncertainties were propagated through to the final risk estimate using Monte Carlo techniques. The geometric mean risk estimates varied from 5.2 x 10(-6) for a hypothetical rancher or laborer working near the RFP to 3.4 x 10(-9) for an infant scenario. The distribution of incremental lifetime cancer incidence risk for the hypothetical rancher was between 1.3 x 10(-6) (5% value) and 2.1 x 10(-5) (95% value). These estimates are similar to or exceed estimated cancer risks posed by releases of radionuclides from the site.     

Use of Monte Carlo Simulation for Human Exposure Assessment at a Superfund Site

This work presents a comparison of probabilistic and deterministic health risk estimates based on data from an industrial site in the northeastern United States. The risk assessment considered exposures to volatile solvents by drinking water ingestion and showering. Probability densities used as inputs included concentrations, contact rates, and exposure frequencies; dose-response inputs were single values. Deterministic risk estimates were calculated by the "reasonable maximum exposure" (RME) approach recommended by the EPA Superfund program. The RME non-carcinogenic risk fell between the 90th and the 95th percentile of the probability density; the RME cancer risk fell between the 95th percentile and the maximum. These results suggest that in this case (1) EPA's deterministic RME risk was reasonably protective, (2) results of probabilistic and deterministic calculations were consistent, and (3) commercially available software Monte Carlo software effectively provided multiple risk estimates recommended by recent EPA guidance.     

Systemic Uptake and Clearance of Chloroform by Hairless Rats Following Dermal Exposure. I. Brief Exposure to Aqueous Solutions

The systemic uptake of chloroform from dilute aqueous solutions into live hairless rats under conditions simulating dermal environmental exposure was studied. Whole blood was sampled during a 30-min immersion of an animal within water containing a known concentration of chloroform and then for 5.5 h following its removal from the bath. The amount of chloroform systemically absorbed was determined by comparing the AUCs of the blood concentration vs. time plots from dermal exposure to that obtained after IV infusion (for a period of 30 min) of an aqueous solution containing a known amount of chloroform (positive control). Although dermal data implied two-compartment disposition characteristics, IV infusion data fit best to a three-compartment disposition. Linear pharmacokinetics was observed both by IV administration and percutaneous absorption at the dose levels studied. Chloroform was detected in the rat blood as early as 4 min following exposure. Our findings suggest that about 10.2 mg of chloroform was systemically absorbed after dermal exposure of a rat to an aqueous solution of 0.44 mg/ml. This amount is substantially higher than the predictions of mathematical risk-models put forth by some investigators. However, when expressed as the "effective" permeability coefficient ( K _p^eff), close agreement was noticed between our value and those estimated by others using physiologically based pharmacokinetic (PBPK) models. Also, in terms of K _p^eff, reasonable agreement existed between our and another investigator's past estimates of uptake based on depletion of bath level of chloroform and the actual uptake measured in our current experiments. The estimated onset of systemic entry seen here is entirely consistent with our estimate of how long it takes to establish the diffusion gradient across the stratum comeum based on tape stripping.     

Cancer risk estimation for mixtures of coal tars and benzo(a)pyrene.

Two-year chronic bioassays were conducted by using B6C3F1 female mice fed several concentrations of two different mixtures of coal tars from manufactured gas waste sites or benzo(a)pyrene (BaP). The purpose of the study was to obtain estimates of cancer potency of coal tar mixtures, by using conventional regulatory methods, for use in manufactured gas waste site remediation. A secondary purpose was to investigate the validity of using the concentration of a single potent carcinogen, in this case benzo(a)pyrene, to estimate the relative risk for a coal tar mixture. The study has shown that BaP dominates the cancer risk when its concentration is greater than 6,300 ppm in the coal tar mixture. In this case the most sensitive tissue site is the forestomach. Using low-dose linear extrapolation, the lifetime cancer risk for humans is estimated to be: Risk < 1.03 x 10(-4) (ppm coal tar in total diet) + 240 x 10(-4) (ppm BaP in total diet), based on forestomach tumors. If the BaP concentration in the coal tar mixture is less than 6,300 ppm, the more likely case, then lung tumors provide the largest estimated upper limit of risk, Risk < 2.55 x 10(-4) (ppm coal tar in total diet), with no contribution of BaP to lung tumors. The upper limit of the cancer potency (slope factor) for lifetime oral exposure to benzo(a)pyrene is 1.2 x 10(-3) per microgram per kg body weight per day from this Good Laboratory Practice (GLP) study compared with the current value of 7.3 x 10(-3) per microgram per kg body weight per day listed in the U.S. EPA Integrated Risk Information System.     

Daily Inhalation Rate and Time‐Activity/Location Pattern in Japanese Preschool Children

Lack of data on daily inhalation rate and activity of children has been an issue in health risk assessment of air pollutants. This study aimed to obtain the daily inhalation rate and intensity and frequency of physical activity in relation to the environment in Japanese preschool children. Children aged four–six years (n= 138) in the suburbs of Tokyo participated in this study, which involved three days' continuous monitoring of physical activity using a tri‐axial accelerometer and parent's completion of a time/location diary during daily life. The estimated three‐day mean daily inhalation rate (body temperature, pressure, saturated with water vapor) was 9.9 ± 1.6 m³/day (0.52 ± 0.09 m³/kg/day). The current daily inhalation rate value of 0.580 m³/kg/day proposed for use in health risk assessment in Japan is confirmed to be valid to calculate central value of inhaled dose of air pollutants in five‐ to six‐year‐old children. However, the 95th percentile daily inhalation rate of 0.83 m³/kg/day based on measurement for five‐year‐old children is recommended to be used to provide an upper bound estimate of exposure that ensure the protection of all five‐ to six‐year‐old children from the health risk of air pollutants. Children spent the majority of their time in sedentary and light level of physical activity (LPA) when indoors, while 85% of their time when outdoors was spent in LPA and moderate‐to‐vigorous physical activity. The results suggest the need to consider variability of minute respiratory ventilation rate according to the environment for more refined short‐term health risk assessment.