Worker studies suggest unique liver carcinogenicity potential of polyvinyl chloride microplastics.

BACKGROUND: Plastic debris pervades our environment. Some breaks down into microplastics (MPs) that can enter and distribute in living organisms causing effects in multiple target organs. MPs have been demonstrated to harm animals through environmental exposure. Laboratory animal studies are still insufficient to evaluate human impact. And while MPs have been found in human tissues, the health effects at environmental exposure levels are unclear. AIM: We reviewed and summarized existing evidence on health effects from occupational exposure to MPs. Additionally, the diverse effects documented for workers were organized by MP type and associated co-contaminants. Evidence of the unique effects of polyvinyl chloride (PVC) on liver was then highlighted. METHODS: We conducted two stepwise online literature reviews of publications focused on the health risks associated with occupational MP exposures. This information was supplemented with findings from animal studies. RESULTS: Our analysis focused on 34 published studies on occupational health effects from MP exposure with half involving exposure to PVC and the other half a variety of other MPs to compare. Liver effects following PVC exposure were reported for workers. While PVC exposure causes liver toxicity and increases the risk of liver cancers, including angiosarcomas and hepatocellular carcinomas, the carcinogenic effects of work-related exposure to other MPs, such as polystyrene and polyethylene, are not well understood. CONCLUSION: The data supporting liver toxicity are strongest for PVC exposure. Overall, the evidence of liver toxicity from occupational exposure to MPs other than PVC is lacking. The PVC worker data summarized here can be useful in assisting clinicians evaluating exposure histories from PVC exposure and designing future cell, animal, and population exposure-effect research studies.

Carcinogenic Air Toxics Exposure and Their Cancer-Related Health Impacts in the United States.

Public health protection from air pollution can be achieved more effectively by shifting from a single-pollutant approach to a multi-pollutant approach. To develop such multi-pollutant approaches, identifying which air pollutants are present most frequently is essential. This study aims to determine the frequently found carcinogenic air toxics or hazardous air pollutants (HAPs) combinations across the United States as well as to analyze the health impacts of developing cancer due to exposure to these HAPs. To identify the most commonly found carcinogenic air toxics combinations, we first identified HAPs with cancer risk greater than one in a million in more than 5% of the census tracts across the United States, based on the National-Scale Air Toxics Assessment (NATA) by the U.S. EPA for year 2005. We then calculated the frequencies of their two-component (binary), and three-component (ternary) combinations. To quantify the cancer-related health impacts, we focused on the 10 most frequently found HAPs with national average cancer risk greater than one in a million. Their cancer-related health impacts were calculated by converting lifetime cancer risk reported in NATA 2005 to years of healthy life lost or Disability-Adjusted Life Years (DALYs). We found that the most frequently found air toxics with cancer risk greater than one in a million are formaldehyde, carbon tetrachloride, acetaldehyde, and benzene. The most frequently occurring binary pairs and ternary mixtures are the various combinations of these four air toxics. Analysis of urban and rural HAPs did not reveal significant differences in the top combinations of these chemicals. The cumulative annual cancer-related health impacts of inhaling the top 10 carcinogenic air toxics included was about 1,600 DALYs in the United States or 0.6 DALYs per 100,000 people. Formaldehyde and benzene together contribute nearly 60 percent of the total cancer-related health impacts. Our study shows that although there are many carcinogenic air toxics, only a few of them affect public health significantly at the national level in the United States, based on the frequency of occurrence of air toxics mixtures and cancer-related public health impacts. Future research is needed on their joint toxicity and cumulative health impacts.

Translational research to develop a human PBPK models tool kit-volatile organic compounds (VOCs).

Toxicity and exposure evaluations remain the two of the key components of human health assessment. While improvement in exposure assessment relies on a better understanding of human behavior patterns, toxicity assessment still relies to a great extent on animal toxicity testing and human epidemiological studies. Recent advances in computer modeling of the dose-response relationship and distribution of xenobiotics in humans to important target tissues have advanced our abilities to assess toxicity. In particular, physiologically based pharmacokinetic (PBPK) models are among the tools than can enhance toxicity assessment accuracy. Many PBPK models are available to the health assessor, but most are so difficult to use that health assessors rarely use them. To encourage their use these models need to have transparent and user-friendly formats. To this end the Agency for Toxic Substances and Disease Registry (ATSDR) is using translational research to increase PBPK model accessibility, understandability, and use in the site-specific health assessment arena. The agency has initiated development of a human PBPK tool-kit for certain high priority pollutants. The tool kit comprises a series of suitable models. The models are recoded in a single computer simulation language and evaluated for use by health assessors. While not necessarily being state-of-the-art code for each chemical, the models will be sufficiently accurate to use for screening purposes. This article presents a generic, seven-compartment PBPK model for six priority volatile organic compounds (VOCs): benzene (BEN), carbon tetrachloride (CCl(4)), dichloromethane (DCM), perchloroethylene (PCE), trichloroethylene (TCE), and vinyl chloride (VC). Limited comparisons of the generic and original model predictions to published kinetic data were conducted. A goodness of fit was determined by calculating the means of the sum of the squared differences (MSSDs) for simulation vs. experimental kinetic data using the generic and original models. Using simplified solvent exposure assumptions for oral ingestion and inhalation, steady-state blood concentrations of each solvent were simulated for exposures equivalent to the ATSDR Minimal Risk Levels (MRLs). The predicted blood levels were then compared to those reported in the National Health and Nutrition Examination Survey (NHANES). With the notable exception of BEN, simulations of combined oral and inhalation MRLs using our generic VOC model yielded blood concentrations well above those reported for the 95th percentile blood concentrations for the U.S. populations, suggesting no health concerns. When the PBPK tool kit is fully developed, risk assessors will have a readily accessible tool for evaluating human exposure to a variety of environmental pollutants.

Health effects of hazardous waste.

Since 1995, the Agency for Toxic Substances and Disease Registry (ATSDR) has evaluated environmental contaminants and human health risks at nearly 3000 sites. Hazardous substances at these sites include newly emerging problems as well as historically identified threats. ATSDR classifies sites according to the degree of hazard they represent to the public. Less than 1% of the sites investigated are considered urgent public health hazards where chemical or physical hazards are at levels that could cause an immediate threat to life or health. Approximately 20% of sites have a potential for long-term human exposures above acceptable risk levels. At almost 40% of sites, hazardous substances do not represent a public health hazard. Completed exposure pathways for contaminants in air, water, and soil have been reported at approximately 30% of evaluated sites. The most common contaminants of concern at these sites include heavy metals, volatile organic compounds, and polychlorinated biphenyls. This article reviews ATSDR's ongoing work by examining the historic hazard of lead, the contemporary hazard of asbestos, and the emerging issue of perchlorate contamination.

A regional approach to assess the impact of living in a chemical world.

In the United States, some 80,000 commercial and industrial chemicals are now in use of which over 30,000 are produced or used in the Great Lakes region. Thus, the environmental quality within the Great Lakes basin has been compromised particularly with respect to persistent toxic substances (PTS). Information derived from wildlife studies, prospective epidemiological and toxicological studies, databases, demographics, and Geographical Information Systems (GIS) demonstrate significant public health implications. Studies of human populations indicate: (a) elevated body burden levels of PTSs, (b) decrease in gestational age, (c) low birth weight (LBW), (d) greater risk of male children with birth defects (OR = 3.01), (e) developmental and neurological deficits, (f) increased risk of infertility, (g) changes in sex ratio, and (h) fluctuations in thyroid hormones. These findings have been identified in vulnerable populations, such as the developing fetus, children, minorities, and men and women of reproductive age who are more susceptible because of their physiologic sensitivity and/or elevated exposure to toxic chemicals. Typically such health effects are assessed on a chemical specific basis; however, most human populations are exposed to hazardous chemicals as mixtures in air, water, soil, and biota. In this article we present an assessment of the potential for joint toxic action of these substances in combinations in which they are typically found. These evaluations represent an integration of all available scientific evidence in accordance with the "NAS paradigm" for risk assessment. In aggregate, our evaluations have demonstrated a need for community-based frameworks and computational techniques to track patterns of environmentally related exposures and associated health effects.