A quantitative screening-level approach to incorporate chemical exposure and risk into alternative assessment evaluations.

As the general public and retailers ask for disclosure of chemical ingredients in the marketplace, a number of hazard screening tools were developed to evaluate the so-called "greenness" of individual chemical ingredients and/or formulations. The majority of these tools focus only on hazard, often using chemical lists, ignoring the other part of the risk equation: exposure. Using a hazard-only focus can result in regrettable substitutions, changing 1 chemical ingredient for another that turns out to be more hazardous or shifts the toxicity burden to others. To minimize the incidents of regrettable substitutions, BizNGO describes "Common Principles" to frame a process for informed substitution. Two of these 6 principles are: "reduce hazard" and "minimize exposure." A number of frameworks have emerged to evaluate and assess alternatives. One framework developed by leading experts under the auspices of the US National Academy of Sciences recommended that hazard and exposure be specifically addressed in the same step when assessing candidate alternatives. For the alternative assessment community, this article serves as an informational resource for considering exposure in an alternatives assessment using elements of problem formulation; product identity, use, and composition; hazard analysis; exposure analysis; and risk characterization. These conceptual elements build on practices from government, academia, and industry and are exemplified through 2 hypothetical case studies demonstrating the questions asked and decisions faced in new product development. These 2 case studies-inhalation exposure to a generic paint product and environmental exposure to a shampoo rinsed down the drain-demonstrate the criteria, considerations, and methods required to combine exposure models addressing human health and environmental impacts to provide a screening level hazard and exposure (risk) analysis. This article informs practices for these elements within a comparative risk context to improve alternatives assessment evaluation and decision making. Integr Environ Assess Manag 2017;13:1007-1022. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Modeling duration of time lived in a residence, a community and mobility in rural areas of Merced and Ventura, California to assess potential health risks to airborne contaminants.

A de novo population mobility survey of 800 households (random digit dialing-based phone interviews) was conducted in high demand areas of the agricultural fumigant, 1,3-dichloropropene (1,3-D) in Merced and Ventura counties of California. The survey included approximately 20 questions relating to the length of time individuals had lived in the high demand areas in each county, and also relating to weekly and annual mobility patterns. Lifetime inhalation exposures to 1,3-D are determined, in part, by the number of years individuals spend in an area where the fumigant is used. The purpose of the survey was to provide location-specific data for probabilistic modeling of long-term inhalation exposures to 1,3-D. The survey found that the majority of residents do not live in a high demand area or in the same house (99.99%) for 70years (a default assumption used by some regulatory agencies). It was also observed that residents move frequently and are mobile day-to-day and week-to-week, within the use area. Finally, estimates of total residency duration, derived from the survey results indicate that median times spent within a high demand area (which could include more than one residential location) were 18 and 26years for Ventura and Merced high demand areas, respectively. The average time spent in the high demand areas was 22 and 27years for the Ventura and Merced community, respectively. Less than 0.01% of the populations in either of the high demand areas spend 70years in the same house.

Evaluation of potential human health effects associated with the agricultural uses of 1,3-D: Spatial and temporal stochastic risk analysis.

Dow AgroSciences (DAS) markets and sells 1,3-Dichloropropene (1,3-D), the active ingredient in Telone®, which is used as a pre-plant soil fumigant nematicide in economically important crops in California. 1,3-D has been regulated as a "probable human carcinogen" and the California Department of Pesticide Regulation limits use of 1,3-D based on human health risk assessments for bystanders. This paper presents a risk characterization for bystanders based on advances in the assessment of both exposure and hazard. The revised bystander risk assessment incorporates significant advances: 1) new data on residency duration and mobility in communities where 1,3-D is in high demand; 2) new information on spatial and temporal concentrations of 1,3-D in air based on multi-year modeling using a validated model; and 3) a new stochastic spatial and temporal model of long-term exposures. Predicted distributions of long-term, chronic exposures indicate that current, and anticipated uses of 1,3-D would result in lifetime average daily doses lower than 0.002mg/kg/d, a dose associated with theoretical lifetime excess cancer risk of <10(-5) to >95% of the local population based on a non-threshold risk assessment approach. Additionally, examination of 1,3-D toxicity studies including new chronic toxicity data and mechanism of action supports the use of a non-linear, threshold based risk assessment approach. The estimated maximum annual average daily dose of <0.0016mg/kg/d derived from the updated exposure assessment was then compared with a threshold point of departure. The calculated margin of exposure is >1000-fold, a clear indication of acceptable risk for human health. In summary, the best available science supports 1,3-D's threshold nature of hazard and the revised exposure assessment supports that current agricultural uses of 1,3-D are associated with reasonable certainty of no harm, i.e., estimated long-term exposures pose insignificant health risks to bystanders even when the non-threshold approach is assumed.

Gender differences in the incidence of background and chemically induced primary pulmonary neoplasms in B6C3F1 mice: a retrospective analysis of the National Toxicology Program (NTP) carcinogenicity bioassays.

The National Toxicology Program (NTP) database of technical reports on carcinogenicity bioassays has been interrogated for the incidence of primary pulmonary neoplasms in B6C3F1 mice. A total of 170 study reports were selected, from studies that completed the in-life phase during 1983-2007, which included neoplasm incidence data for 180 control groups comprising both male and female mice. The incidence (median and inter-quartile range) of males with alveolar/bronchiolar adenoma was 16% (12-20%), and for females it was 5% (2-8%); the incidence of males with alveolar/bronchiolar carcinoma was 8% (4-12%), and for females it was 2% (0-4%); and the incidence of males with combined alveolar/bronchiolar adenoma or carcinoma was 24% (18-30%), and for females it was 8% (6-12%). Comparing the incidence of animals bearing these lesions on a per study basis showed the median incidence in males to be 3.0-fold, 2.0-fold, and 2.8-fold higher than in females. The incidence of other primary pulmonary neoplasms was <10% of the alveolar/bronchiolar neoplasms. Comparison of gender-specific response to lung tumorigens showed that the increase in incidence of tumors above control levels was greater in females than in males.

Derivation of single layer clothing penetration factors from the pesticide handlers exposure database.

Quantitative characterization of the penetration of chemical residues through various types and configurations of clothing is an important underpinning of mitigation strategies to reduce dermal exposure to occupational cohorts. The objective of the evaluation presented herein is the development of pesticide clothing penetration (or conversely protection) factors for single layer clothing (i.e., long-sleeved shirt, long pants; gloves are not included) based on dermal exposure monitoring data (passive dosimetry) included in the Environmental Protection Agency's Pesticide Handlers Exposure Database (PHED). The analysis of penetration per replicate was conducted by comparison of the inside and outside (total deposition), expressed as mug/cm(2), for each replicate pair of dermal dosimeters. Clothing penetration was investigated as a function of job classification, dosimetry sampling method, body part, application method, and type of formulation. Grand mean single layer clothing penetration values for patch (n=2029) and whole-body (n=100) dosimeter samples from PHED were 12.12 (SE=0.33; SD=15.02) and 8.21 (SE=1.01; SD=10.14) percent, respectively. Linear regression was used to evaluate clothing penetration as a function of outer dosimeter loading. The regression analysis supports the hypothesis that single layer clothing penetration increases with decreasing outer dosimeter loading.

Recommended relative potency factors for 2,3,4,7,8-pentachlorodibenzofuran: the impact of different dose metrics.

The recent National Toxicology Program (NTP) cancer bioassays for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF) permit a reevaluation of the current TEF value of 4-PeCDF. The data also allow for the derivation of relative potency factors (RPFs) for cancer, which are based not only on administered dose but also on potentially more informative dose metrics, such as liver concentration, area under the liver concentration curve, and lifetime average body burden. Our analyses of these data indicate that chi-squared tests of observed versus predicted liver tumor incidence for 4-PeCDF reject the current TEF value of 0.5 value as too high. 4-PeCDF RPFs were derived using estimation methods that either did or did not assume parallelism of the 4-PeCDF and TCDD dose-response curves. The resulting parallelism-based RPFs for administered dose, liver concentration at terminal sacrifice, liver concentration AUC, and lifetime average body burden are 0.26, 0.014, 0.021, and 0.036, respectively. The administered dose RPF estimate is approximately one-half the current TEF value of 0.5. However, the use of administered dose fails to take into account pharmacokinetic differences between congeners and the generally acknowledged belief that body burden or some other measure of cumulative dose is more appropriate for estimating the health risk posed by persistent chemicals. The other three dose metrics do account for these important factors, and the corresponding RPFs are at least 10-fold lower than the current TEF for 4-PeCDF. In summary, our analyses support an administered dose TEF no greater than 0.25 and one in the 0.05-0.1 range for internal dose metrics such as lifetime average liver concentration or body burden.

Background concentrations of dioxins, furans, and PCBs in Sprague-Dawley rats and juvenile swine.

In preparation for a study of the relative oral bioavailability of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in soils (typically containing less than 1 ppb 2,3,7,8-tetrachlo-rodibenzo-p-dioxin [TCDD] toxic equivalents [TEQ]), the background concentrations of PCDD/Fs and selected polychlorinated biphenyls (PCBs) were measured in liver and adipose tissue from female Sprague-Dawley rats and juvenile swine after 30 d of ingesting laboratory chow. The measured concentrations of TCDD and other PCDD/Fs in rat livers were severalfold less than previously reported in the literature for control (unexposed) laboratory rodents. The concentrations of PCDD/Fs and selected PCBs in livers of swine were three- to fourfold lower than those reported for rats. The lower concentrations found in this study compared to previous findings may be due to inadvertent laboratory contamination in previous studies or to declining levels of PCDD/Fs in laboratory feed, which parallel the declines in emissions, general environmental levels, and human food and tissue levels of PCDD/Fs.