Cumulative Risk Assessment Approach Research Articles

Are Phthalate Exposure Related to Oxidative Stress in Children and Adolescents with Asthma? A Cumulative Risk Assessment Approach

Childhood asthma has become one of the most common chronic diseases in children and adolescents. However, few case–control studies investigating the relationship between phthalate exposure and asthma in children and adolescents have been conducted, especially in Asia. Therefore, we assessed the potential associations between phthalate exposure and asthma among children and adolescents in Taiwan. Because various demographic and environmental variables may influence the incidence and prognosis of asthma, we performed a case–control study with propensity score matching. Out of 615 Childhood Environment and Allergic Diseases Study participants, we conditionally matched 41 children with clinically diagnosed asthma with 111 controls. We then analyzed 11 phthalate metabolites by using liquid chromatography with tandem mass spectrometry. Compared with the control group, the median urinary phthalate levels for most phthalate metabolites in the case group were slightly increased, including monomethyl phthalate, mono-n-butyl phthalate, monobenzyl phthalate, monoethylhexyl phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, and mono-(2-carboxymethylhexyl) phthalate. Hence, our results suggest that phthalate exposure may be associated with the development of asthma. In addition, prenatal environmental factors, such as active or passive smoking during pregnancy, may increase the risk of asthma.

A Cumulative Risk Perspective for Occupational Health and Safety (OHS) Professionals.

Cumulative risk assessment (CRA) addresses the combined risk associated with chemical and non-chemical exposures. Although CRA approaches are utilized in environmental and ecological contexts, they are rarely applied in workplaces. In this perspectives article, we strive to raise awareness among occupational health and safety (OHS) professionals and foster the greater adoption of a CRA perspective in practice. Specifically, we provide an overview of CRA literature as well as preliminary guidance on when to consider a CRA approach in occupational settings and how to establish reasonable boundaries. Examples of possible workplace co-exposures and voluntary risk management actions are discussed. We also highlight important implications for workplace CRA research and practice. In particular, future needs include simple tools for identifying combinations of chemical and non-chemical exposures, uniform risk management guidelines, and risk communication materials. Further development of practical CRA methods and tools are essential to meet the needs of complex and changing work environments.

Chemical-by-chemical and cumulative risk assessment of residential indoor exposure to semivolatile organic compounds in France

BackgroundThe toxic effects of environmental exposure to chemicals are increasingly being studied and confirmed, notably for semivolatile organic compounds (SVOCs). These are found in many products and housing materials, from which they are emitted to indoor air, settled dust and other surfaces. ObjectivesThe objective of this work is to assess the human health risk posed by residential indoor exposure to 32 SVOCs, assessed in previous nationwide studies. MethodsA chemical-by-chemical risk assessment, using a hazard quotient (HQ) or excess risk (ER) method, was supplemented by a cumulative risk assessment (CRA). For CRA, a hazard index (HI) method, as well as higher tier approaches using relative potency factors (RPFs) or toxic equivalency factors (TEFs) were used for the following endpoints: neurotoxicity, reproductive toxicity, genotoxicity and immunotoxicity. ResultsHQs were above 1 for 50% of French children from birth to 2 years for BDE 47, and for 5% of children for lindane and dibutyl phthalate (DBP). Corresponding hazards are reprotoxic for BDE 47 and DBP, and immunotoxic for lindane. The CRA approach provided additional information of reprotoxic risks (HI > 1) that may occur for 95% of children and for 5% of the offspring for pregnant women's exposure. The SVOCs contributing most to these risks were PCB 101 and 118, BDE 47, and DBP. The higher tier CRA approaches showed that exposure to dwellings' SVOC mixtures were of concern for 95% of children for neurotoxic compounds having effects linked with neuronal death. To a lesser extent, effects mediated by the aryl hydrocarbon receptor (AhR) or by a decrease in testosterone levels may concern 5% of children and adults. Lastly, unacceptable immunotoxic risk related to exposure to 8 indoor PCBs was also observed for 5% of children. ConclusionsIn view of uncertainties related to compounds' toxicity for humans, these results justify the implementation of preventive measures, as well as the production of more standardized and comprehensive toxicological data for some compounds.

Community, State, and Federal Approaches to Cumulative Risk Assessment: Challenges and Opportunities for Integration

Community, state, and federal approaches to conventional and cumulative risk assessment (CRA) were described and compared to assess similarities and differences, and develop recommendations for a consistent CRA approach, acceptable across each level as a rigorous scientific methodology, including partnership formation and solution development as necessary practices. Community, state, and federal examples were described and then summarized based on their adherence to CRA principles of: (1) planning, scoping, and problem formulation; (2) risk analysis and ranking, and (3) risk characterization, interpretation, and management. While each application shared the common goal of protecting human health and the environment, they adopted different approaches to achieve this. For a specific project-level analysis of a particular place or instance, this may be acceptable, but to ensure long-term applicability and transferability to other projects, recommendations for developing a consistent approach to CRA are provided. This approach would draw from best practices, risk assessment and decision analysis sciences, and historical lessons learned to provide results in an understandable and accepted manner by all entities. This approach is intended to provide a common ground around which to develop CRA methods and approaches that can be followed at all levels.

The Invisible Threat: Bisphenol-A and Phthalates in Environmental Justice Communities

Low-income, communities of color have historically been exposed to disproportionate amount of toxins from air, water, and land. While the environmental justice (EJ) movement has fought to eliminate environmental concerns, less attention has been given to the health impacts of phthalates and bisphenol-A (BPA) found in common products used in the home, workplace, and schools. Our review of 23 research articles shows that a potential connection between BPA and phthalates exposure in consumer products to adverse health outcomes needs to be further explored. Revisions of the Toxic Substances Control Act are necessary and it is imperative that future policy efforts recognize and use a cumulative risk assessment approach to understand and address the negative health impacts brought on by both chemicals.

An exposure-based framework for grouping pollutants for a cumulative risk assessment approach: Case study of indoor semi-volatile organic compounds

Humans are exposed to a large number of contaminants, many of which may have similar health effects. This paper presents a framework for identifying pollutants to be included in a cumulative risk assessment approach. To account for the possibility of simultaneous exposure to chemicals with common toxic modes of action, the first step of the traditional risk assessment process, i.e. hazard identification, is structured in three sub-steps: (1a) Identification of pollutants people are exposed to, (1b) identification of effects and mechanisms of action of these pollutants, (1c) grouping of pollutants according to similarity of their mechanism of action and health effects. Based on this exposure-based grouping we can derive “multi-pollutant” toxicity reference values, in the “dose–response assessment” step. The approach proposed in this work is original in that it is based on real exposures instead of a limited number of pollutants from a unique chemical family, as traditionally performed. This framework is illustrated by the case study of semi-volatile organic compounds in French dwellings, providing insights into practical considerations regarding the accuracy of the available toxicological information. This case study illustrates the value of the exposure-based approach as opposed to the traditional cumulative framework, in which chemicals with similar health effects were not always included in the same chemical class.

Phthalates in German daycare centers: Occurrence in air and dust and the excretion of their metabolites by children (LUPE 3)

Phthalates have been used for decades in large quantities, leading to the ubiquitous exposure of the population.In an investigation of 63 German daycare centers, indoor air and dust samples were analyzed for the presence of 10 phthalate diesters. Moreover, 10 primary and secondary phthalate metabolites were quantified in urine samples from 663 children attending these facilities. In addition, the urine specimens of 150 children were collected after the weekend and before they went to daycare centers.Di-isobutyl phthalate (DiBP), dibutyl phthalate (DnBP), and di-2-ethylhexyl phthalate (DEHP) were found in the indoor air, with median values of 468, 227, and 194ng/m3, respectively. In the dust, median values of 888mg/kg for DEHP and 302mg/kg for di-isononyl phthalate (DiNP) were observed. DnBP and DiBP were together responsible for 55% of the total phthalate concentration in the indoor air, whereas DEHP and DiNP were responsible for 70% and 24% of the total phthalate concentration in the dust.Median concentrations in the urine specimens were 44.7μg/l for the DiBP monoester, 32.4μg/l for the DnBP monoester, and 16.5μg/l and 17.9μg/l for the two secondary DEHP metabolites. For some phthalates, we observed significant correlations between their concentrations in the indoor air and dust and their corresponding metabolites in the urine specimens using bivariate analyses. In multivariate analyses, the concentrations in dust were not associated with urinary metabolite excretion after controlling for the concentrations in the indoor air.The total daily “high” intake levels based on the 95th percentiles calculated from the biomonitoring data were 14.1μg/kg b.w. for DiNP and 11.9μg/kg b.w. for DEHP. Compared with tolerable daily intake (TDI) values, our “high” intake was 62% of the TDI value for DiBP, 49% for DnBP, 24% for DEHP, and 9% for DiNP. For DiBP, the total daily intake exceeded the TDI value for 2.4% of the individuals. Using a cumulative risk-assessment approach for the sum of DEHP, DnBP, and DiBP, 20% of the children had concentrations exceeding the hazard index of one. Therefore, a further reduction of the phthalate exposure of children is needed.

Exposure to phthalates in 5–6 years old primary school starters in Germany—A human biomonitoring study and a cumulative risk assessment

We determined the internal exposure of 111 German primary school starters by analyzing urinary metabolites of six phthalates: butyl benzyl phthalate (BBzP), di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), di (2-ethylhexyl) phthalate (DEHP), di-iso-nonyl phthalate (DiNP) and di-iso-decylphthalate (DiDP). From the urinary metabolite levels, we calculated daily intakes and related these values to Tolerable Daily Intake (TDI) values. By introducing the concept of a relative cumulative Tolerable Daily Intake (TDI(cum)) value, we tried to account for the cumulative exposure to several of the above-mentioned phthalates. The TDI(cum) was derived as follows: the daily intake (DI) calculated from the metabolite level was divided by the TDI for each phthalate; this ratio was multiplied by 100% indicating the TDI percentage for which the DI accounted. Finally the % TDIs of the different phthalates were totalled to get the TDI(cum). A TDI(cum) above 100% is a potential cause for concern. We confirmed the ubiquitous exposure of the children to all phthalates investigated. Exposures were within range of levels previously reported for GerES, albeit slightly lower. Regarding daily intakes, two children exceeded the TDI for DnBP, whereas one child closely approached the TDI for DEHP. 24% of the children exceeded the TDI(cum) for the three most critical phthalates: DEHP, DnBP and DiBP. Furthermore, 54% of the children had total exposures that used up more than 50% the TDI(cum). Therefore, the overall exposure to a number of phthalates, and the knowledge that these phthalates (and other anti-androgens) act in a dose-additive manner, urgently warrants a cumulative risk assessment approach.

A Feasibility Study of Cumulative Risk Assessment Methods for Drinking Water Disinfection By-Product Mixtures

Humans are exposed daily to complex mixtures of chemicals, including drinking water disinfection by-products (DBPs) via oral, dermal, and inhalation routes. Some positive epidemiological and toxicological studies suggest reproductive and developmental effects and cancer are associated with consumption of chlorinated drinking water. Thus, the U.S. Environmental Protection Agency (EPA) conducted research to examine the feasibility of evaluating simultaneous exposures to multiple DBPs via all three exposure routes. A cumulative risk assessment approach was developed for DBP mixtures by combining exposure modeling and physiologically based pharmacokinetic modeling results with a new mixtures risk assessment method, the cumulative relative potency factors (CRPF) approach. Internal doses were estimated for an adult female and an adult male, each of reproductive age, and for a child (age 6 yr) inclusive of oral, dermal, and inhalation exposures. Estimates of the daily internal doses were made for 13 major DBPs, accounting for activity patterns that affect the amount of human contact time with drinking water (e.g., tap water consumed, time spent showering), building characteristics (e.g., household air volumes), and physicochemical properties of the DBPs (e.g., inhalation rates, skin permeability rates, blood:air partition coefficients). A novel cumulative risk assessment method, the CRPF approach, is advanced that integrates the principles of dose addition and response addition to produce multiple-route, chemical mixture risk estimates using total absorbed doses. Research needs to improve this approach are presented.

Mechanistic approaches for mixture risk assessments—present capabilities with simple mixtures and future directions

Mechanistic studies with simple mixtures have provided insights into the nature of interactions among chemicals that lead to non-additive effects and have elucidated the exposure conditions under which interactions are likely to occur. This paper discusses studies on four mixtures: (1) 1,1-dichloroethylene and trichloroethylene, (2) carbon tetrachloride and Kepone, (3) hexane and methyl- n-butylketone, and (4) coplanar and non-coplanar polychlorinated biphenyls. These mechanistic studies show that interactions should be described at the level of target tissue dose and are best categorized as either pharmacokinetic (PK) or pharmacodynamic (PD) interactions. In PK interactions the presence of a second chemical alters the kinetics such that a unit of administered dose no longer produces a unit of dose at the target tissue. In PD interactions, the presence of other compounds alters the PDs such that a unit tissue dose no longer produces a unit of response. Physiologically based pharmacokinetic (PBPK) models for mixtures have become important tools for predicting conditions under which interactions are likely to alter the assumption of additivity and have permitted calculation of interaction thresholds with more confidence. New cumulative risk assessment approaches have provided opportunities to classify compounds on the basis of similar chemistry-based modes of action (cholinesterase inhibitors) or similar physiological modes of action (diverse chemicals that alter a common biological outcome, such as defeminization of the developing nervous system). The latter examples present challenges for expanding our risk assessment paradigm to focus on the biology of responses more than on the kinetics of the xenobiotics. Some of the future advances in mixture research will depend on progress in systems biology, a discipline that integrates information across multiple level of biological organization producing PD models of normal function and assessing conditions under which exposures to chemicals lead to the perturbations sufficiently great to produce toxicity and disease. We describe briefly the elements of a systems biology approach for assessing the interactions between various PCB congeners.