Review of Information Resources to Support Human Exposure Assessment Models

Efforts to model human exposures to chemicals are growing more sophisticated and encompass increasingly complex exposure scenarios. The scope of such analyses has increased, growing from assessments of single exposure pathways to complex evaluations of aggregate or cumulative chemical exposures occurring within a variety of settings and scenarios. In addition, quantitative modeling techniques have evolved from simple deterministic analyses using single point estimates for each necessary input parameter to more detailed probabilistic analyses that can accommodate distributions of input parameters and assessment results. As part of an overall effort to guide development of a comprehensive framework for modeling human exposures to chemicals, available information resources needed to derive input parameters for human exposure assessment models were compiled and critically reviewed. Ongoing research in the area of exposure assessment parameters was also identified. The results of these efforts are summarized and other relevant information that will be needed to apply the available data in a comprehensive exposure model is discussed. Critical data gaps in the available information are also identified. Exposure assessment modeling and associated research would benefit from the collection of additional data as well as by enhancing the accessibility of existing and evolving information resources.     

Organ and effective dose rate coefficients for submersion exposure in occupational settings

External dose coefficients for environmental exposure scenarios are often computed using assumption on infinite or semi-infinite radiation sources. For example, in the case of a person standing on contaminated ground, the source is assumed to be distributed at a given depth (or between various depths) and extending outwards to an essentially infinite distance. In the case of exposure to contaminated air, the person is modeled as standing within a cloud of infinite, or semi-infinite, source distribution. However, these scenarios do not mimic common workplace environments where scatter off walls and ceilings may significantly alter the energy spectrum and dose coefficients. In this paper, dose rate coefficients were calculated using the International Commission on Radiological Protection (ICRP) reference voxel phantoms positioned in rooms of three sizes representing an office, laboratory, and warehouse. For each room size calculations using the reference phantoms were performed for photons, electrons, and positrons as the source particles to derive mono-energetic dose rate coefficients. Since the voxel phantoms lack the resolution to perform dose calculations at the sensitive depth for the skin, a mathematical phantom was developed and calculations were performed in each room size with the three source particle types. Coefficients for the noble gas radionuclides of ICRP Publication 107 (e.g., Ne, Ar, Kr, Xe, and Rn) were generated by folding the corresponding photon, electron, and positron emissions over the mono-energetic dose rate coefficients. Results indicate that the smaller room sizes have a significant impact on the dose rate per unit air concentration compared to the semi-infinite cloud case. For example, for Kr-85 the warehouse dose rate coefficient is 7% higher than the office dose rate coefficient while it is 71% higher for Xe-133.     

Tables of dose conversion coefficients for estimating internal and external radiation exposures to terrestrial and aquatic biota

Dose conversion coefficients (DCCs) for assessment of internal and external radiation exposures to terrestrial and aquatic biota are compiled for 75 radionuclides, for 14 terrestrial and 22 aquatic reference organisms. DCC values for internal exposure are calculated based on a homogeneous distribution of the radionuclides in both types of organisms. DCC values for external exposure of aquatic organisms are calculated for complete immersion in water. For external exposure of terrestrial organisms the soil is considered as a planar and homogenously contaminated volume source with a surface roughness of 3 mm and a thickness of 10 cm, respectively. For in-soil-organisms, DCC values for external exposure are given assuming that these organisms live in the middle of a uniformly contaminated 50 cm-thick soil layer. The tables can be used for assessment of exposures of animals and plants living in various habitats. The list of considered organisms covers the Reference Animals and Plants as adopted by the ICRP.     

A review of the USEPA's single breath canister (SBC) method for exhaled volatile organic biomarkers

Exhaled alveolar breath can provide a great deal of information about an individual's health and previous exposure to potentially harmful xenobiotic materials. Because breath can be obtained non-invasively and its constituents directly reflect concentrations in the blood, its use has many potential applications in the field of biomarker research. This paper reviews the utility and application of the single breath canister (SBC) method of alveolar breath collection and analysis first developed by the US Environmental Protection Agency (USEPA) in the 1990s. This review covers the development of the SBC technique in the laboratory and its application in a range of field studies. Together these studies specifically show how the SBC method (and exhaled breath analysis in general) can be used to clearly demonstrate recent exposure to volatile organic compounds, to link particular activities to specific exposures, to determine compoundspecific uptake and elimination kinetics, and to assess the relative importance of various routes of exposure (i.e. dermal, ingestion, inhalation) in multipathway scenarios. Specific investigations covered in this overview include an assessment of exposures related to the residential use of contaminated groundwater, exposures to gasoline and fuel additives at self-service gas stations, swimmers' exposures to trihalomethanes, and occupational exposures to jet fuel.     

PARATI – a dynamic model for radiological assessments in urban areas

The structure and mathematical model of PARATI, a detailed computer programme developed for the assessment of the radiological consequences of an accidental contamination of urban areas, is described with respect to the scenarios used for the estimation of exposure fields in a village or town, the models for the initial and secondary contamination with the radionuclide ¹³⁷Cs, the concepts for calculating the resulting radiation exposures and the changes with time of the contamination and radiation fields. Kerma rates at various locations in tropical urban areas are given, and the contribution of different contaminated surfaces to these rates after dry or wet deposition are discussed. Received: 12 April 1996 / Accepted in revised form: 30 August 1996     

Native American Exposure to 131Iodine from Nuclear Weapons Testing in Nevada

A great deal of work has been done to reconstruct doses from Nevada Test Site fallout, yet the unique exposures of Native American communities continue to be neglected. It is possible to estimate the exposures of these communities through a process of collaborative information gathering and analysis. This article builds on a previous exercise that demonstrated the substantial doses received through the consumption of contaminated game. The updated model includes new information on the deposition of ¹³¹iodine, an assessment of the neonatal thyroid doses received through breast milk, an exploration of the effect of population mobility on dose estimates, and estimates of thyroid cancer risk. All thyroid dose estimates from the rabbit exposure pathway are comparable in magnitude to National Cancer Institute comprehensive dose estimates that assume exposure to contaminated milk from backyard cows and goats. Dose estimates from the rabbit exposure pathway are larger than estimated doses from store-bought milk by an average factor of six. Taking historical population mobility patterns into account may result in slightly lower estimates of dose. The quantification of this exposure pathway is considered be an advance toward a more appropriate dose reconstruction for communities with diets high in wild game.     

Effective dose rate coefficients for exposure to contaminated soil

The Oak Ridge National Laboratory Center for Radiation Protection Knowledge has undertaken calculations related to various environmental exposure scenarios. A previous paper reported the results for submersion in radioactive air and immersion in water using age-specific mathematical phantoms. This paper presents age-specific effective dose rate coefficients derived using stylized mathematical phantoms for exposure to contaminated soils. Dose rate coefficients for photon, electron, and positrons of discrete energies were calculated and folded with emissions of 1252 radionuclides addressed in ICRP Publication 107 to determine equivalent and effective dose rate coefficients. The MCNP6 radiation transport code was used for organ dose rate calculations for photons and the contribution of electrons to skin dose rate was derived using point-kernels. Bremsstrahlung and annihilation photons of positron emission were evaluated as discrete photons. The coefficients calculated in this work compare favorably to those reported in the US Federal Guidance Report 12 as well as by other authors who employed voxel phantoms for similar exposure scenarios.     

Occupational exposures during abdominal fluoroscopically guided interventional procedures for different patient sizes — A Monte Carlo approach

In this study we evaluated the occupational exposures during an abdominal fluoroscopically guided interventional radiology procedure. We investigated the relation between the Body Mass Index (BMI), of the patient, and the conversion coefficient values (CC) for a set of dosimetric quantities, used to assess the exposure risks of medical radiation workers. The study was performed using a set of male and female virtual anthropomorphic phantoms, of different body weights and sizes. In addition to these phantoms, a female and a male phantom, named FASH3 and MASH3 (reference virtual anthropomorphic phantoms), were also used to represent the medical radiation workers. The CC values, obtained as a function of the dose area product, were calculated for 87 exposure scenarios. In each exposure scenario, three phantoms, implemented in the MCNPX 2.7.0 code, were simultaneously used. These phantoms were utilized to represent a patient and medical radiation workers. The results showed that increasing the BMI of the patient, adjusted for each patient protocol, the CC values for medical radiation workers decrease. It is important to note that these results were obtained with fixed exposure parameters.     

Gamma-H2AX-based dose estimation for whole and partial body radiation exposure

Most human exposures to ionising radiation are partial body exposures. However, to date only limited tools are available for rapid and accurate estimation of the dose distribution and the extent of the body spared from the exposure. These parameters are of great importance for emergency triage and clinical management of exposed individuals. Here, measurements of γ-H2AX immunofluorescence by microscopy and flow cytometry were compared as rapid biodosimetric tools for whole and partial body exposures. Ex vivo uniformly X-irradiated blood lymphocytes from one donor were used to generate a universal biexponential calibration function for γ-H2AX foci/intensity yields per unit dose for time points up to 96 hours post exposure. Foci--but not intensity--levels remained significantly above background for 96 hours for doses of 0.5 Gy or more. Foci-based dose estimates for ex vivo X-irradiated blood samples from 13 volunteers were in excellent agreement with the actual dose delivered to the targeted samples. Flow cytometric dose estimates for X-irradiated blood samples from 8 volunteers were in excellent agreement with the actual dose delivered at 1 hour post exposure but less so at 24 hours post exposure. In partial body exposures, simulated by mixing ex vivo irradiated and unirradiated lymphocytes, foci/intensity distributions were significantly over-dispersed compared to uniformly irradiated lymphocytes. For both methods and in all cases the estimated fraction of irradiated lymphocytes and dose to that fraction, calculated using the zero contaminated Poisson test and γ-H2AX calibration function, were in good agreement with the actual mixing ratios and doses delivered to the samples. In conclusion, γ-H2AX analysis of irradiated lymphocytes enables rapid and accurate assessment of whole body doses while dispersion analysis of foci or intensity distributions helps determine partial body doses and the irradiated fraction size in cases of partial body exposures.     

Microbial aerosol generation during laboratory accidents and subsequent risk assessment

AIM: To quantify microbial aerosols generated by a series of laboratory accidents and to use these data in risk assessment. METHODS AND RESULTS: A series of laboratory accident scenarios have been devised and the microbial aerosol generated by them has been measured using a range of microbial air samplers. The accident scenarios generating the highest aerosol concentrations were, dropping a fungal plate, dropping a large bottle, centrifuge rotor leaks and a blocked syringe filter. Many of these accidents generated low particle size aerosols, which would be inhaled into the lungs of any exposed laboratory staff. Spray factors (SFs) have been calculated using the results of these experiments as an indicator of the potential for accidents to generate microbial aerosols. Model risk assessments have been described using the SF data. CONCLUSIONS: Quantitative risk assessment of laboratory accidents can provide data that can aid the design of containment laboratories and the response to laboratory accidents. SIGNIFICANCE AND IMPACT OF THE STUDY: A methodology has been described and supporting data provided to allow microbiological safety officers to carry out quantitative risk assessment of laboratory accidents.     

Importance of dose‐response model form in probabilistic risk assessment: A case study of health effects from methylmercury in fish

We compared the effect of uncertainty in dose‐response model form on health risk estimates to the effect of uncertainty and variability in exposure. We used three different dose‐response models to characterize neurological effects in children exposed in utero to methylmercury, and applied these models to calculate risks to a native population exposed to potentially contaminated fish from a reservoir in British Columbia. Uncertainty in model form was explicitly incorporated into the risk estimates. The selection of dose‐response model strongly influenced both mean risk estimates and distributions of risk, and had a much greater impact than altering exposure distributions. We conclude that incorporating uncertainty in dose‐response model form is at least as important as accounting for variability and uncertainty in exposure parameters in probabilistic risk assessment.     

Subsistence Exposure Scenarios for Tribal Applications

The article provides an overview of methods that can be used to develop exposure scenarios for unique tribal natural resource usage patterns. Exposure scenarios are used to evaluate the degree of environmental contact experienced by people with different patterns of lifestyle activities, such as residence, recreation, or work. In 1994, U.S. President Bill Clinton's Executive Order 12898 recognized that disproportionately high exposures could be incurred by people with traditional subsistence lifestyles because of their more intensive contact with natural resources. Since then, we have developed several tribal exposure scenarios that reflect tribal-specific traditional lifeways. These scenarios are not necessarily intended to capture contemporary resource patterns, but to describe how the resources were used before contamination or degradation, and will be used once again in fully traditional ways after cleanup and restoration. The direct exposure factors for inhalation and soil ingestion rates are the same in each tribal scenario, but the diets are unique to each tribe and its local ecology, natural foods, and traditional practices. Scenarios, in part or in whole, also have other applications, such as developing environmental standards, evaluating disproportionate exposures, developing sampling plans, planning for climate change, or evaluating service flows as part of natural resource damage assessments.     

Prevalence of dermal pathway dominance in risk assessment of contaminated soils: A survey of superfund risk assessments, 1989–1992

Exposure to soil‐borne contaminants can occur through ingestion, inhalation and/or dermal absorption. A study was undertaken to assess the relative frequency with which dermal exposures are predicted to pose the greatest risk attributable to contaminated soils in Superfund risk assessments. Screening of over 200 risk assessments from the period 1989–1992 resulted in identification of 37 sites at which projected lifetime excess cancer risks attributed to dermal contact with soil were greater than the nominal regulatory threshold of 1.10^‐4. At 19 of these sites, the dermal/soil pathway is estimated to contribute the largest carcinogenic risk associated with surface soil contamination, and may therefore drive cleanup of that medium. At 9 of the sites, the dermal/soil pathway is predicted to present a higher carcinogenic risk than any other pathway. Chemical contaminant type and estimates of soil adherence and surface area exposed appear to be the primary factors that distinguish sites at which dermal/soil pathway carcinogenic risk estimates are elevated relative to other exposure pathways. Quantification of exposure parameters, especially those related to behavior, remains a significant need.     

Inter-rater agreement of assessed prenatal maternal occupational exposures to lead

BACKGROUND: Industrial hygienists' assessments of prenatal occupational exposures based on parental job histories is a promising approach for population-based case-control studies of birth defects and other perinatal outcomes. However, evaluations of inter-rater agreement of such assessments have been limited. METHODS: We examined inter-rater agreement of occupational lead exposure assessments of maternal job reports by industrial hygienists in a population-based case-control study of parental occupational lead exposure and low birth weight. A total of 178 jobs with potential exposure to lead during the 6 months before pregnancy to the end of pregnancy were examined. Three industrial hygienists evaluated these jobs independently for exposure to lead including probability of exposure, type of exposure, route of entry, exposure frequency, duration, and intensity. Inter-rater agreement of these assessments beyond chance was evaluated using the kappa statistic (kappa). RESULTS: In general, inter-rater agreement was greater for assessment of direct exposures than assessment of indirect exposures. However, inter-rater agreement varied with the lead exposure metric under consideration, being: 1) fair to good for type of direct exposure (i.e., inorganic or organic), respiratory exposure and frequency of exposure to direct inorganic lead, hours per day of direct (i.e., inorganic or organic), and intensity of direct inorganic exposure; 2) poor for probability and type of indirect exposure (inorganic or organic); and 3) indeterminate for frequency of direct organic exposure, frequency of indirect exposures (organic or inorganic), and intensity of direct exposures (organic or inorganic). CONCLUSION: Retrospective assessment of maternal prenatal exposures to lead by industrial hygienists can provide some reliable metrics of exposure for studies of perinatal outcomes. Reliability studies of such exposure assessments may be useful for: quantifying the reliability of derived exposure metrics; identifying exposure metrics for exposure-outcome analyses; and determining the reliability of prenatal occupational exposures to other agents of interest.     

Conjugative Plasmid in Corynebacterium flaccumfaciens subsp. oortii That Confers Resistance to Arsenite, Arsenate, and Antimony(III)

The membrane filter (MF) method for detection and enumeration of coliform bacteria in drinking water requires that the coliforms both grow and produce a green metallic sheen when the filter is incubated on modified Endo medium at 35 degrees C for 22 h. Large numbers of noncoliform bacteria, which are enumerated by the standard plate count (SPC) technique, can interfere with the detection of coliforms on MF. This paper presents quantitative evidence from laboratory experiments on the interference of specific SPC bacteria on coliform colony sheen production on MF. Pseudomonas aeruginosa and Aeromonas hydrophila caused significant reductions in Escherichia coli sheen colony counts when present at 3,000 and 220 per filter, respectively. The Flavobacterium sp. and Bacillus sp. selected for this study from SPC did not interfere with coliform colony sheen production. Excessive crowding of E. coli and Enterobacter cloacae colonies on MF also caused a reduction in the number of colonies that produced sheen. Even when there was no crowding (14 colonies per filter), only a fraction of the E. cloacae colonies produced sheen colonies on modified Endo medium.     

Calculating the radiological parameters used in non-human biota dose assessment tools using ERICA Tool and site-specific data

The substantial complexity in ecosystem–radionuclide interactions is difficult to be represented in terms of radiological doses. Thus, radiological dose assessment tools use typical exposure situations for generalized organisms and ecosystems. In the present study, site-specific data and radioactivity measurements of terrestrial organisms (grass and herbivore mammals) and abiotic components (soil) are provided. The retrieved data are used in combination with the ERICA Assessment Tool for calculation of radiological parameters. The process of radionuclide transfer within ecosystem components is represented using concentration ratios (CRs), while for the calculation of dose rates the dose conversion coefficient (DCC) methodology is applied. Comparative assessments are performed between the generic and assessment-specific radiological parameters and between the resulting dose rates. Significant differences were observed between CRs calculated in this study and those reported in the literature for cesium and thorium, which can easily be explained. On the other hand, CRs calculated for radium are in very good agreement with those reported in the literature. The DCCs exhibited some small differences between the reference and the assessment-specific organism due to mass differences. The differences were observed for internal and external dose rates, but they were less pronounced for total dose rates which are typically used in the assessment of radiological impact. The results of the current work can serve as a basis for further studies of the radiological parameters in environments that have not been studied yet.     

Exposure and Health Risk from Swimming in Outdoor Pools Contaminated by Trichloroethylene

A method was developed that evaluated the exposure and health risk to children from swimming in outdoor pools filled with contaminated water. It was found that dermal absorption of trichloroethylene (TCE) was significantly larger than the inhalation component of the exposures. It was estimated that the inhalation route accounted for only 1% of the total exposure, whereas accidental ingestion was 7% of the child's total intake and the dermal absorbed dose was 92% of the total exposure. The relative percentage of the total exposure estimated for each exposure route indicated that the dermal exposure route and accidental ingestion of pool water should not be ignored for volatile compounds when evaluating exposure.

The method utilized was simple enough to use computer spreadsheets for the calculations and can be easily adapted to various swimming scenarios and age groups. This method also included an assessment of the uncertainty in the exposure and risk estimates. The range of estimated exposures was 40 μ g to 442 μ g of TCE per swimming season. All values in this range were below the health benchmark for both non-carcinogenic and carcinogenic endpoints.     

Lack of effect of butylparaben and methylparaben on the reproductive system in male rats

BACKGROUND: Parabens are widely used preservatives in cosmetics and pharmaceutical products, and approved as food additives. Parabens have been considered safe for these uses for many years. Recently, adverse effects on male reproductive parameters in rats have been reported when parabens were given orally for 8 weeks starting at three weeks of age. Our studies used two representative parabens, methyl‐ and butylparaben, to try to replicate these studies and thereby evaluate potential reproductive effects in male Wistar rats. METHODS: Diets containing 0, 100, 1000 or 10,000 ppm of either butyl‐ or methylparaben were fed to male rats for eight weeks. Rats were 22 days of age at the start of exposure. Parameters evaluated included organ weights, histopathology of reproductive tissues, sperm production, motility, morphology and reproductive hormone levels (butylparaben only). RESULTS: None of the parameters evaluated for either paraben showed compound‐ or dosage‐dependent adverse effects. Metabolism experiments of butylparaben indicate that it is rapidly metabolized by non‐specific esterases to p‐hydroxybenzoic acid and butanol, neither of which is estrogenic. CONCLUSIONS: Exposure to methyl‐ or butylparaben in the diet for eight weeks did not affect any male reproductive organs or parameters at exposures as high as 10,000 ppm, corresponding to a mean daily dose of 1,141.1±58.9 or 1,087.6±67.8 mg/kg/day for methyl‐ and butylparaben, respectively. The rapid metabolism of parabens by esterases probably explains why these weakly estrogenic substances elicit no in vivo effects when administered by relevant exposure routes (i.e., topical and oral). Birth Defects Research (Part B) 2008. 2008 Wiley‐Liss, Inc.     

Does the Emperor Have Any Clothes: Using Mechanistic Information or Doing Houdini Risk Assessments?

Risk assessment research rarely quells controversy. Mega-mouse, and mega-rat, experiments contradicted a threshold for carcinogenesis, yet thresholds are still argued. High to low dose continuity of response from cigarette smoking to environmental tobacco smoke, and from occupational asbestos exposure to take-home asbestos, contradict thresholds in people. Nevertheless, mechanistic hypotheses allege “Houdini Risk Assessments”, which make risks disappear or allow industries to escape from protecting workers. Despite concerns for animal-to-human extrapolations, priority occupational exposures with sufficient or substantial evidence of carcinogenicity in people not addressed by new exposure limits include silica, sulfuric acid mist, chromates, diesel particulate matter, particulate matter generally, metalworking fluids, welding fume, and formaldehyde. “Houdini Risk Assessments” are exercises in “anti-hypothesis generation”: ignore selected tumor sites and types; ignore data from people (as with formaldehyde and diesel); choose the most resistant species in laboratory tests; select biochemical parameters in which the most resistant species resembles people; assume a mechanism that gives threshold or steep exposure response for carcinogenic effect; and reduce estimated people risk by the parameter ratio to the most resistant species. NORA research should focus on quantitative reconciliation of laboratory and epidemiology studies, and develop a counter “anti-hypothesis” generation research agenda for key exposure circumstances.