Risk Assessment Of Dermal Exposure Research Articles

Assessing the health risks of dermal exposure to heavy metals dust among nail salon technicians.

Nail salon technicians are susceptible to potential exposure to a diverse array of hazardous chemicals in the form of dust or vapors. One of the main routes of exposure is dermal contact. The aim of present study was to health risk assessment of dermal exposure to heavy dust containing heavy metals in nail salon technicians. Dust sampling was done on the work surface of 20 available nail salon technicians. The concentration of five metals including cadmium, lead, chromium, nickel, and manganese were determined using ICP-MS. Afterwards, the United States Environmental Protection Agency (USEPA) guideline was used to estimate the potential health risks, including carcinogenic and non-carcinogenic risks, associated with the analyzed metals. Results indicated the mean concentrations of Pb, Cd, Ni, Cr and Mn were 0.7953±0.4373, 0.0952±0.0264, 0.7666±0.8629, 0.4900±0.5994 and 1.134±0.4736, respectively. The hazard quotient (HQ) of all metals was within the permissible value, while hazard index (HI) was greater than 1. The probability of cancer risk (CR) resulting from dermal exposure to Ni, Cd and Cr exceeded the acceptable risk levels (10-6-10-4), but CR calculated for Pb was less than allowable value. Implementation of engineering controls such as downdraft vented nail tables and portable source capture systems is necessary. Besides, the use of personal protective equipment such as disposable nitrile gloves, N95 respirator masks, and ensuring proper training on safe work practices is recommended.

Occurrence of trace elements in print paper products: Non-carcinogenic risk assessment through dermal exposure

Over time, the risk assessment of dermal exposure to pollutants in print paper products has received considerable attention. Most studies have focused on organic pollutants, especially bisphenol A (BPA). However, little is known about the levels of trace elements in print paper products, despite the knowledge that these elements are components of printing inks and toners. This study was aimed at determining the concentrations of trace elements in 5 types of paper products, namely bulletins, magazines, special events program booklets, handbills, and newspapers. The average daily intake (ADI) of each element was subsequently estimated through dermal exposure to the papers. The detection frequency of the elements of interest was high (nearly 100%) in most paper products, with the exception of chromium, whose detection was low. In contrast, Ag was not detected in any sample. The levels of the elements in the paper products were low and comparable to those found in other personal and consumer products with the potential for skin contact. The range values of estimated ADIs were 1.70–3.90E-08, 2.30–18.2E-10, 2.60–16.4E-09, 3.65–5.75E-08, 1.29–4.38E-08, 6.23–15.6E-10, 1.51–2.80E-10, 1.43–9.16E-09, 0.00–9.47E-09, and 4.68–220E-08 mg/kg bw/day for Mn, Co, Ni, Cu, Zn, As, Cd, Pb, Cr and Fe respectively. These values were well below the dermal standard reference doses (RfD) for each element. The present results indicate that dermal exposure to trace elements from print paper products was low and does not pose significant risks for toxic (non-carcinogenic) effects on humans.

Estimate of the maximum amount of dust adhering to skin and the upper limit of dust-skin adherence factor for young adults: An example from Changchun, China

Contaminants present in dust adhering to the skin can pose a significant risk to human health through dermal absorption and hand-to-mouth contact. The adhesion capacity of dust differs significantly from that of soil due to its physicochemical properties. Therefore, applying the raw soil exposure parameters to estimate the health risks associated with dermal exposure to dust may lead to erroneous conclusions. In this study, we quantified the maximum amount of dust that adhered to the skin (MADmax) and the upper limit of dust-skin adherence factor (DSAFmax) in 26 adults using element markers as a proxy for dust. The volunteers were exposed to dust and rinse water samples were collected from their hands, forearms, lower legs, and feet. We analyzed both the raw dust samples and the rinse water samples for 11 element markers, including Be, V, Cr, Mn, Co, Ni, Cu, Zn, Se, Ba, and Pb. The results showed that the MADmax of indoor dust and outdoor dust increased by 0.08–0.62 mg and 0.33–0.56 mg following a 1 cm2 increase in skin surface area, respectively. Based on best dust element markers, the body part-weighted dust-skin adherences (WDSAFmaxs) of indoor dust and outdoor dust were 0.35 and 0.64 mg/cm2, respectively. A smaller particle size and higher moisture content resulted in a larger DSAFmax. Only when indoor dust concentrations exceed 24.2 mg/m3 or outdoor dust concentrations exceed 44.3 mg/m3, can the WDSAFmax be applied directly in the health risk assessment of dermal exposure to dust. The method from this study can be re-applied in different regions, and the adherence data can help to improve future studies on the health effects of dermal exposure to dust.

The Toxicological Risk Assessment of Dermal Exposure of Patients Exposed to Lead and Cadmium Due to Application of Ointments with Marjoram Herb Extract (Majoranae herbae extractum).

Potential heavy metal impurities (HMI) in pharmaceuticals/pharmaceutical products/drugs based on plant raw materials (e.g., herbs) are an important problem in the pharmaceutical industry; however, there is a lack of scientific articles on the comprehensive toxicological risk assessment of HMI in ointment applied dermally. To make the appropriate toxicological risk assessment, we consider: (1) the raw results of the levels of lead and cadmium in the ointments (metal per kg of mass), (2) one-time administration of the applied ointment, (3) daily exposure of Pb and Cd in the applied ointments according to the maximum daily dose of applied pharmaceuticals, including transcutaneous penetration, (4) human health risk assessment based on the USEPA model, and 5) the margin of exposure (MoE). The raw results indicated that lead (7.05-101.78 µg/kg) and cadmium (0.32-0.81 µg/kg) were present in all samples. The levels of analyzed HMI (independently of the producer and declared composition) were similar. Pb and Cd contamination associated with daily doses met the standards of the ICH Q3D (R2) guide on elemental impurities in pharmaceuticals, including the cutaneous route of administration. Taking into account the daily amount of lead and cadmium (ointment, ug/day) the results were satisfactory, confirming the safety of marjoram herb extract ointments available in Polish pharmacies according to the ICH guideline Q3D (R2) on elemental impurities. The HQ values obtained for Pb and Cd in all samples were less than 1; therefore, exposure to these HMI would not cause a health risk based on the USEPA model strategy. Furthermore, the obtained values of MoE for Pb and Cd in ointments were above 100, so exposure to these elements would not cause a health risk based on the MoE-based strategy. The original contribution of this work is that this is the first study on the triple approach strategy to evaluate the safety of heavy metal impurities in traditional herbal medicinal products applied dermally in solid form (ointments with marjoram herb extract). The research is novel and has not been previously published; The proposed procedure includes transcutaneous penetration of heavy metal (Pb and Cd) impurities described for the first time in the literature.

Health Risk Assessment of Dermal Exposure to Polycyclic Aromatic Hydrocarbons from the Use of Infant Diapers.

In September 2021, the European Chemicals Agency evaluated a dossier for restricting polycyclic aromatic hydrocarbons (PAHs) in infant diapers and concluded that risks were not demonstrated, because of inconclusive exposure data. To fill this gap, we measured the 16 priority PAHs of the U.S. Environmental Protection Agency in the diaper core of four brands and in the sheets and fastening tapes of six brands of commercially available diapers. Health risks were conservatively assessed by assuming that dermally absorbed PAHs can cause both local (skin cancer) and systemic critical effects (neurobehavioral changes). Total concentrations of PAHs in the diaper core and top sheet, the only significant contributors to skin exposure, averaged 26.5 μg/kg and 66.6 μg/kg, respectively. Excess skin cancer risks and hazard quotients for neurobehavioral effects calculated with the daily dose of total PAHs from the combined diaper core and top sheet averaged 1.44 × 10-7 and 1.19 × 10-2, respectively. The median daily doses of total PAHs and of its benzo[a]pyrene-equivalent from breast milk estimated worldwide are 171 and 30 times greater than that from the combined diaper core and top sheet, respectively. Altogether, these findings indicate that trace levels of PAHs found in infant diapers are unlikely to pose health risks.

Health risk assessment of dermal exposure to Chlorpyrifos among children in agricultural areas in Sakon Nakhon Province, Thailand

Chlorpyrifos is a widely used agricultural insecticide. Chlorpyrifos exposure affects brain development and children’s overall health. The objective of this study was to assess the health risks from skin exposure to chlorpyrifos and to investigate the factors associated with chlorpyrifos exposure among children in agricultural areas. Residual chlorpyrifos samples were collected from the hands and feet of 130 children (aged 1–3) to analyze chlorpyrifos content using high-pressure liquid chromatography with a diode array detector. Chlorpyrifos residues were detected on the skin of 73.1% of the children tested. The health risk assessment of non-cancerous effects showed that children had dermal chlorpyrifos exposure at 1.46 × 10−5 mg/kg-day, and the hazard quotient (HQ) of child dermal chlorpyrifos exposure was 0.03, which is an acceptable level. The frequency of accompanying parents to pesticide-sprayed areas was significantly associated with dermal chlorpyrifos exposure levels in children (ORadjust =1.44, 95%CI =1.02–2.03). However, children in agricultural areas may be subject to additional health risks from exposure to other pesticides through respiration and ingestion. Therefore, they should not be allowed to accompany their parents to agricultural areas, and a program to prevent pesticides from affecting children in these areas should be developed.

The Toxicological Risk Assessment of Dermal Exposure of Patients Exposed to Nickel and Chromium due to Application of Ointments with Marjoram Herb Extract (Majoranae Herbae Extractum) Available in Polish Pharmacies

For elemental impurities that have been studied for transcutaneous absorption, the available data are rarely suitable for proper toxicological risk assessment — there are multiple factors that can influence this dermal absorption. Hence, in our studies, we applied generic and conservative approach — cutaneous permitted daily exposure (CPDE) described in International Conference on Harmonisation’s Q3D Guideline on Elemental Impurities (ICH Q3D). The aim of this article is toxicological risk assessment (TRA) of dermal exposure of patients exposed to nickel and chromium due to application of ointments with Marjoram herb extract (Majoranae herbae extractum) available in Polish pharmacies (n = 5, because only five manufacturers produce this kind of pharmaceutical products in Poland). To make the appropriate TRA approach, we considered (1) raw results (metal per kg of ointment), (2) one-time administration of applied ointments, and (3) daily exposure versus CPDE. Due to the fact the concentrations of Ni generally present in cutaneous products as impurities are not considered sufficient to induce sensitization, the cutaneous and transcutaneous concentration limits (CTCLs) approach was applied for this element assessment. The toxicological analysis was carried out using microwave-assisted wet digestion with concentrated nitric acid and electrothermal atomization atomic absorption spectrometry. Our results show that the ointments with Marjoram herb extract from pharmacies in Poland represent a potential health hazard to patients; however, there may be a requirement for the monitoring of impurities of nickel in future. To the best of our knowledge, this paper is the first study about nickel and chromium content in ointments with Marjoram herb extract (Majoranae herbae extractum).

Health Risk Assessment of Dermal Exposure to Heavy Metals Content of Chemical Hair Dyes

Contamination of hair dyes to heavy metals can threaten consumer's health. We investigated the concentrations of some important heavy metals in hair dyes and evaluates their non-carcinogenic effects. The most commonly used hair dyes were determined through questioners and 32 samples were collected from the market of Tehran in 2014. The concentration of 10 heavy metals (Fe, Ag, Co, Cr, Mn, Ba, Cd, Cu, Pb, and Al) was determined using ICP-MS. Based on the obtained data from distributed questionnaires and Monte Carlo simulation, the exposure to the evaluated heavy metals was estimated. Besides, using hazard quotient (HQ) and chronic hazard (HI), the risk of non-carcinogenic effects of investigated hair dyes consumption was specified. Results indicated the average concentrations of Al, Ba, and Fe as 0.54, 0.86, and 1.19 mg kg-1 and those of Cd, Cu, and Pb as 0.45, 61.32, and 185.34 μg kg-1, respectively. Pb with HQ of 7.46e-4 had the highest risk and Fe with HQ of 3.4e-6 had the lowest level of risk. Among the investigated dyes, the ones made by Iran (HI=2.8e-4) and the dark brown color (HI=1.93e-4) had the highest level of risk among all the studied samples. Two indices of HI and HQ showed that heavy metal contents in the investigated samples had not probable non-carcinogenic risks for the consumers of these products.

Percutaneous penetration of drugs applied in transdermal delivery systems: an in vivo based approach for evaluating computer generated penetration models

Human skin is a viable pathway for administration of therapeutics. Transdermal delivery systems (TDS) have been approved by the US-FDA since 1981. To enable the risk assessment of dermal exposure, predictive mathematical models are used. In this work the accuracy of predicted flux of the models is compared to experimental human in vivo data of drugs applied in US-FDA approved TDS. A database of pharmacokinetic data of drugs applied in TDS was used and updated. Three mathematical models (QSAR) were used to calculate predicted fluxes, and compared to the human in vivo data. For more than half of the drugs applied in TDS, the predicted flux by the mathematical models was an underestimation compared to the flux calculated with the experimental in vivo data. The flux was over- or underestimated by a factor 10–100. All mathematical models were significantly correlated with the experimental in vivo data. The process of percutaneous penetration has several influencing factors, TDS minimize some of these factors. Limitations are discussed. Further research is needed, with a focus on validation and standardization of the permeability coefficient. This work offers observations that should give a stimulus for refinement on the appropriate usage and limitations of mathematical models.

Health risk assessment of dermal exposure to chlorpyrifos among applicators on rice farms in Ghana

Generally, there is limited information on pesticide absorbed dose levels and health risk attributable to the dermal route of exposure among applicators. The objective of this study was to evaluate the absorbed dose levels and consequent health risk from dermal exposure to chlorpyrifos among applicators on rice farms in Ghana. The whole-body dosimetry technique was used to capture chlorpyrifos residues penetrating the applicators’ clothing and reaching their skin, as well as residues reaching uncovered body areas of the applicators. Acute (ADDD) and chronic (LADDD) absorbed dose levels of chlorpyrifos were estimated from the residues and plotted as cumulative probability distributions. Health risk from chlorpyrifos exposure was characterized using the Hazard Quotient (HQ) technique. Three of the four acute exposure guideline values used in the study indicated that applicators, represented by the median-exposed (ADDD, 15 μg/kg/day) and the 5% - highly exposed (ADDD, 27 μg/kg/day) groups were at high risk of acute adverse health effects due to chlorpyrifos exposure, with HQ values ranging from 1.5 to 5 and 2.7 to 9, respectively. Regarding chronic adverse health effects, none of the guideline values suggested risk among the median-exposed group (LADDD, 0.3 μg/kg/day), with HQ values ranging from 0.03 to 1. However, two of the chronic exposure guideline values suggested that the 5%- highly exposed group (LADDD, 0.6 μg/kg/day) may be adversely affected, with HQ values ranging from 1.2 to 2. These findings highlight the importance of the dermal route as a major pesticide exposure pathway and suggest possible exposure minimization strategies.

Human health risk assessment for dermal exposure to d-limonene in cosmetics

Human health risk assessment for dermal exposure to d-limonene in cosmetics

Biological monitoring to assess dermal exposure to ethylene oxide vapours during an incidental release

During a short incident in an ethylene oxide (EO) producing plant, EO vapour was released under high pressure. Operators wore full respiratory protection during repairs to fix the leak. To check the adequacy of the applied personal protective equipment and to address concerns about potential dermal exposure and subsequent uptake of EO, biological monitoring was applied by determination of the haemoglobin adducts of EO in blood. Based on the results of the biomonitoring, a risk assessment of dermal exposure to EO vapour was made.Calculations to estimate dermal exposure, based on two recently published models and using the relevant physical–chemical properties of EO, indicate that the dermal contribution to total exposure is expected to be negligible under normal operating circumstances. However, the models indicate that under accidental circumstances of product spillage, when high air concentrations can build up quickly and where incident response is conducted under respiratory protection with independently supplied air, the systemic exposure resulting from dermal absorption may reach levels of concern.The model estimates were compared to the actual biomonitoring data in the operators involved in the accidental release of EO vapour. The results suggest that when incidental exposures to high EO vapour concentrations (several thousand ppm) occur during periods in excess of 20–30min, additional risk management measures, such as wearing chemical impervious suits, should be considered to control dermal uptake of EO.

Risk Assessment for Dermal Exposure of Organochlorine Pesticides for Local Fishermen in the Rangsit Agricultural Area, Central Thailand

ABSTRACT Organochlorine pesticides (OCPs) used in agriculture and for public health purposes were banned in Thailand over the past decade; however, their persistent residues have been found in several agricultural areas of the country. This may result in adverse effects to human populations. This study investigated the concentration of organochlorine pesticides residues (OCPRs) in surface water and evaluated the potential cancer risk associated with dermal contact of the local fisherman fishing in the Khlong 7 canal, Rangsit agricultural area, central Thailand. Water samples were extracted using liquid-liquid extraction (LLE) and then analyzed by gas chromatography with microelectron capture detector (μ -ECD). The results show that low concentrations of OCPRs were detected in parts per billion (ppb or ng/ml) levels, that is, ∑ Endosulfan (α -, β -, and -sulfate) 0.082 ng/ml > DDT and derivatives 0.019 ng/ml > ∑ HCH (α -, γ -, β -, and δ -HCH) 0.014 ng/ml > aldrin and dieldrin 0.007 ng/ml > heptachlor and heptachlor epoxide 0.0068 ng/ml > endrin and endrin aldehyde 0.005 ng/ml > methoxychlor 0.001 ng/ml, respectively. Using the worst-case scenario defined as the reasonable maximum exposure (RME) to assess the potential cancer risk, five OCPs (dieldrin, 4,4′ -DDT, β -HCH, heptachlor, and heptachlor epoxide) may pose a risk of concern on a lifetime human carcinogenesis greater than one in a million.

Biomonitoring as a tool in the human health risk characterization of dermal exposure

Dermal exposure is an important factor in risk characterization. In occupational settings it becomes relatively more important because of the continuous reduction in inhalation exposure. In the public health arena, dermal exposure may also form a significant contribution to the total exposure. Dermal exposure, however, is difficult to assess directly because it is determined by a host of factors, which are difficult to quantify. As a consequence, dermal exposure is often estimated by application of models for external exposure. In combination with modeled or measured data for percutaneous penetration, these provide an estimate for the internal exposure that is directly related to the systemic effects. The advantages and drawbacks of EASE (Estimation and Assessment of Substance Exposure) and RISKOFDERM (Risk Assessment of Occupational Dermal Exposure), two models for external exposure that are mentioned in the Technical Guidance Document for the European Union risk assessments performed under the Existing Substances Regulation (EEC/793/93), are discussed. Although new chemicals regulation (REACh, 1907/2006/EC) is now in place in the European Union, the principles applied under the previous legislation do not change and the same models will continue to be used. The results obtained with these models for styrene, 2-butoxyethanol, and 1-methoxy-2-propanol in specific exposure scenarios are compared with an alternative method that uses biomonitoring data to assess dermal exposure. Actual external exposure measurements combined with measured or modeled percutaneous penetration data give acceptable results in risk assessment of dermal exposure, but modeled data of external dermal exposure should only be used if no other data are available. However, if available, biomonitoring should be considered the method of choice to assess (dermal) exposure.

Evaluation of in-vivo animal and in-vitro models for prediction of dermal absorption in man

Risk assessment of dermal exposure to chemicals requires percutaneous absorption data to link the external exposure to the systemic uptake. The most reliable data on percutaneous absorption are obtained from in-vivo human volunteer studies. In addition to ethical constrains, the conduct of these studies is not feasible for the large number of industrial chemicals in use today. Therefore, there is an increasing need for alternative methods to determine percutaneous absorption such as in-vitro assays and methods performed in vivo in experimental animals. In this article, recent comparative in-vitro and in-vivo studies on percutaneous absorption have been addressed with emphasis on the factors that may affect the predictive value of the in-vitro models. Furthermore, the use of animal models, in particular the rat skin, in prediction of percutaneous absorption in the human skin has been reviewed. In-vitro assays showed to be largely influenced by the experimental circumstances, such as type and thickness of the skin, receptor fluid, and the way in which percutaneous absorption is calculated. Rat skin showed consistently to be more permeable than human skin. However, the difference between human and rat skin does not show a consistent pattern between chemicals hampering prediction of human percutaneous absorption. To increase predictive value of in-vitro and animal models, the influence of experimental factors on the percutaneous absorption should be systematically investigated by comparison with human in-vivo data, resulting in more prescriptive guidelines.

Methods for measuring in-vivo percutaneous absorption in humans

In-vivo human data on percutaneous absorption are scarce, although they are indispensable for health risk assessment of dermal exposure. In addition, they are considered to be the gold standard for the evaluation of in-vitro systems as well as predictive mathematical models. Dermal absorption in vivo can be assessed using different approaches. The most used methods for determination of in-vivo dermal absorption are the measurement of the parent chemical and/or its metabolite level in biological material, the microdialysis technique and stratum corneum tape stripping. Recently, the non-invasive spectrophotometric methods based on infrared and Raman spectroscopy showed themselves as promising tools for studying percutaneous absorption though these approaches are still in their developmental stages and requires further optimization and validation. The aim of this article is to review different methods for determination of percutaneous absorption in vivo in humans. The advantages and limitations are discussed with respect to generating data for comparison with in-vitro or predictive mathematical models or health risk assessment of chemicals. Furthermore, the importance of the volunteer experiments in generating relevant data for human risk assessment as well as for the development and implementation of biological monitoring in occupational settings will be addressed.

The influence of water mixtures on the dermal absorption of glycol ethers

Glycol ethers are solvents widely used alone and as mixtures in industrial and household products. Some glycol ethers have been shown to have a range of toxic effects in humans following absorption and metabolism to their aldehyde and acid metabolites. This study assessed the influence of water mixtures on the dermal absorption of butoxyethanol and ethoxyethanol in vitro through human skin. Butoxyethanol penetrated human skin up to sixfold more rapidly from aqueous solution (50%, 450 mg/ml) than from the neat solvent. Similarly penetration of ethoxyethanol was increased threefold in the presence of water (50%, 697 mg/ml). There was a corresponding increase in apparent permeability coefficient as the glycol ether concentration in water decreased. The maximum penetration rate of water also increased in the presence of both glycol ethers. Absorption through a synthetic membrane obeyed Fick's Law and absorption through rat skin showed a similar profile to human skin but with a lesser effect. The mechanisms for this phenomenon involves disruption of the stratum corneum lipid bilayer by desiccation by neat glycol ether micelles, hydration with water mixtures and the physicochemical properties of the glycol ether-water mixtures. Full elucidation of the profile of absorption of glycol ethers from mixtures is required for risk assessment of dermal exposure. This work supports the view that risk assessments for dermal contact scenarios should ideally be based on absorption data obtained for the relevant formulation or mixture and exposure scenario and that absorption derived from permeability coefficients may be inappropriate for water-miscible solvents.

Dermal route in systemic exposure.

To evaluate risk from dermal exposure, the amount of material on the skin must first be measured. The potential for dermal uptake must then be assessed for the potential health effects from systemic exposure. No standard methods exist for studying these processes, and published data are not comparable because of the different techniques used. Future validated methodology should provide a sound scientific basis for risk assessment. Methods for measuring skin and surface contamination will require development of reference contaminated surfaces and skin as part of quality control procedures. Biological monitoring is a valuable tool in the assessment of dermal absorption, in contributing to the validation of in vitro techniques, and in risk assessment and management. It will be necessary to conduct detailed investigations to support risk assessment for dermal exposure. Ultimately, predictive models will be established for exposure and for dermal absorption to support a generic approach and allow risk assessment strategies appropriate to actual workplace situations.

Estimation of Octanol-Water Partition Coefficients and Correlation with Dermal Absorption for Several Polyhalogenated Aromatic Hydrocarbons

Estimation of Octanol-Water Partition Coefficients and Correlation with Dermal Absorption for Several Polyhalogenated Aromatic Hydrocarbons. Jackson, J. A., Diliberto, J. J., and Birnbaum, L. S. (1993). Fundam. Appl. Toxicol. 21, 334-344.n-Octanol-Water partition coefficients (Kow) were experimentally estimated for; 2,3,7,8-tetrachloro and 2,3,7,8-tetrabromodibenzo-p-dioxin; 2,3,7,8-tetrachloro-, 2,3,7,8-tetrabromo-, and 1,2,7,8-tetrabromodibenzofuran; 1,2,3,7,8-pentachloro-, 1,2,3,7,8-pentabromo-, 2,3,4,7,8 pentachloro-, and 2,3,4,7,8-pentabromodibenzofuran; 1,2,4,6,8,9-hexachlorodibenzofuran (HxCDF), and 3,4,3′,4′-tetrachlorobiphenyl (3,4,3′,4′TCB). The method involved correlation of literature Kow with reverse-phase high-performance liquid chromotography (RP-HPLC) retention time for a series of 23 calibration standards and estimation of Kow for test compounds from measured RP-HPLC retention. Retention times for all standards and test chemicals were measured in duplicate on the same octadecasilane (C18) reverse-phase column with an isocratic 85:15 methanol:water mobile phase; solutes were detected by uv absorbance (254 nm). Literature log Kow values used for the calibration standards had been measured exclusively by the generator column method. Log Kow estimates for the test compounds in the present study ranged from 5.45 for 3,4,3′,4′-TCB to 6.81 for HxCDF. Kow estimates were then plotted against laboratory data for the in vivo 3-day dermal absorption of single equimolar doses (200 pmol and 20 nmol, or ∼1 nmol/kg and ∼0.1 μmol/kg) of selected test compounds in male F344 rats. Strong inverse correlations were found between octanol-water partition coefficient estimates and single-dose dermal absorption for most of the compounds studied. In addition, RP-HPLC retention time itself appeared to be as equally suited as Kow to such correlations with dermal absorption. The structure-activity relationships suggested in this study were sought in order to explain observed differences in the dermal absorption of polyhalogenated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners differing in number, position, and/or type (Cl or Br) of halogen substituents. Moreover, these results should be of predictive value in the risk assessment of dermal exposure to polychlorinated dibenzop-dioxins, dibenzofurans, biphenyls, and their brominated analogues.

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.