Genotoxicity as a toxicologically relevant endpoint to inform risk assessment: A case study with ethylene oxide.

The purpose of the present investigation is to analyze the in vivo genotoxicity dose-response data of ethylene oxide (EO) and the applicability of the derived point-of-departure (PoD) values when estimating permitted daily exposure (PDE) values. A total of 40 data sets were identified from the literature, and benchmark dose analyses were conducted using PROAST software to identify a PoD value. Studies employing the inhalation route of exposure and assessing gene or chromosomal mutations and chromosomal damage in various tissues were considered the most relevant for assessing risk from EO, since these effects are likely to contribute to adverse health consequences in exposed individuals. The PoD estimates were screened for precision and the values were divided by data-derived adjustment factors. For gene mutations, the lowest PDE was 285 parts per trillion (ppt) based on the induction of lacI mutations in the testes of mice following 48 weeks of exposure to EO. The corresponding lowest PDE value for chromosomal mutations was 1,175 ppt for heritable translocations in mice following 8.5 weeks of EO exposure. The lowest PDE for chromosomal aberrations was 238 ppt in the mouse peripheral blood lymphocytes following 48 weeks of inhalation exposure. The diverse dose-response data for EO-induced genotoxicity enabled the derivation of PoDs for various endpoints, tissues, and species and identified 238 ppt as the lowest PDE in this retrospective analysis.

Air ions and respiratory function outcomes: a comprehensive review.

BACKGROUND: From a mechanistic or physical perspective there is no basis to suspect that electric charges on clusters of air molecules (air ions) would have beneficial or deleterious effects on respiratory function. Yet, there is a large lay and scientific literature spanning 80 years that asserts exposure to air ions affects the respiratory system and has other biological effects. AIMS: This review evaluates the scientific evidence in published human experimental studies regarding the effects of exposure to air ions on respiratory performance and symptoms. METHODS: We identified 23 studies (published 1933-1993) that met our inclusion criteria. Relevant data pertaining to study population characteristics, study design, experimental methods, statistical techniques, and study results were assessed. Where relevant, random effects meta-analysis models were utilized to quantify similar exposure and outcome groupings. RESULTS: The included studies examined the therapeutic benefits of exposure to negative air ions on respiratory outcomes, such as ventilatory function and asthmatic symptoms. Study specific sample sizes ranged between 7 and 23, and studies varied considerably by subject characteristics (e.g., infants with asthma, adults with emphysema), experimental method, outcomes measured (e.g., subjective symptoms, sensitivity, clinical pulmonary function), analytical design, and statistical reporting. CONCLUSIONS: Despite numerous experimental and analytical differences across studies, the literature does not clearly support a beneficial role in exposure to negative air ions and respiratory function or asthmatic symptom alleviation. Further, collectively, the human experimental studies do not indicate a significant detrimental effect of exposure to positive air ions on respiratory measures. Exposure to negative or positive air ions does not appear to play an appreciable role in respiratory function.

Tracking polychlorinated biphenyls (PCBs) congener patterns in Newark Bay surface sediment using principal component analysis (PCA) and positive matrix factorization (PMF).

PCB congener data for Newark Bay surface sediments were analyzed using PCA and PMF, and relationships between the outcomes from these two techniques were explored. The PCA scores plot separated the Lower Passaic River Mouth samples from North Newark Bay, thus indicating dissimilarity. Although PCA was able to identify subareas in the Bay system with specific PCB congener patterns (e.g., higher chlorinated congeners in Elizabeth River), further conclusions reading potential PCB source profiles or potential upland source areas were not clear for the PCA scores plot. PMF identified five source factors, and explained the Bay sample congener profiles as a mix of these Factors. This PMF solution was equivalent to (1) defining an envelope that encompasses all samples on the PCA scores plot, (2) defining source factors that plot on that envelope, and (3) explaining the congener profile for each Bay sediment sample (inside the scores plot envelope) as a mix of factors. PMF analysis allowed identifying characteristic features in the source factor congener distributions that allowed tracking of source factors to shoreline areas where PCB inputs to the Bay may have originated. The combined analysis from PCA and PMF showed that direct discharges to the Bay are likely the dominant sources of PCBs to the sediment. Review of historical upland activities and regulatory files will be needed, in addition to the PCA and PMF analysis, to fully reconstruct the history of operations and PCB releases around the Newark Bay area that impacted the Bay sediment.

Water adherence factors for human skin.

On incidental dermal exposure to chemicals in water, a key exposure factor is the amount of water adhering to skin. Although soil adherence factors have been developed for risk assessment, measurements of water adherence on human skin have not been described. In the Environmental Protection Agency's (EPA's) dermal risk assessment guidance, dermal dose from environmental exposures is based upon the flux rate across the skin, which assumes that an unlimited amount of chemical is available for absorption. This assumption is applicable to certain exposure scenarios such as swimming and bathing. However, exposures to contaminated water frequently involve scenarios where the available chemical is limited by the amount of water adhering to the skin, for example, during accidental splashes.

Importance of considering the framework principles in risk assessment for metals.

The recent EPA Framework for Metals Risk Assessment provides the opportunity for contextual risk assessment for sites impacted by metals (such as the depicted Dauntless Mine in Colorado).

Development of a refined database of mammalian relative potency estimates for dioxin-like compounds.

The toxic equivalency factor (TEF) approach has been widely accepted as the most feasible method available at present for evaluating potential health risks associated with exposure to mixtures of dioxin-like compounds (DLCs). The current mammalian TEFs for the DLCs were established by the World Health Organization (WHO) following the meeting of an international expert panel in June of 1997. The TEFs recommended by WHO were determined based on a consensus of scientific judgment and were presented as point estimates. However, the relative potency estimates (REPs) underlying the TEFs were derived from a heterogeneous data set and often span several orders of magnitude. In this article, we present a refined database of mammalian REPs that we believe will facilitate better characterization of the variability and uncertainty inherent in the data. The initial step involved reviewing the REP database used by the WHO panel during its review in 1997. A set of criteria was developed to identify REPs that were determined to be the most representative measure of a biological response and of adequate quality for use in quantitative analyses. REPs were determined to be inappropriate for use in quantitative analyses if any of the established exclusion criteria were met. Comparison of data records to the established exclusion criteria resulted in the identification of a substantial number of REPs believed to be inappropriate for use in quantitative analyses. Next, studies published after 1997 were added to the database. The availability of such a refined database will improve risk assessment for this class of compounds by including additional information from new studies and facilitating the use of quantitative approaches in the further development of TEFs.

Quantitation of polychlorinated biphenyls in fish for human cancer risk assessment: a comparative case study.

A range of analytical options is available for the quantification of environmental polychlorinated biphenyls (PCBs). The PCBs can be quantified as Aroclor mixtures, as individual PCB congeners, or as PCB homologues. The methodological choice is driven by many considerations, including cost, but it is important to note that the risk assessment methods recommended by the U.S. Environmental Protection Agency (U.S. EPA) have specific and varying requirements for these analytical endpoints. The toxic equivalency approach is recommended for settings where the original Aroclor mixtures have been heavily degraded or weathered. Because this method only addresses the dioxin-like fraction of the PCB mass, the remaining PCB congeners need to be quantified and assessed separately, in a manner that is consistent with current U.S. EPA guidance. In this present analysis, we examined various methods for estimating a total nondioxin-like PCB mass in fish tissue samples from a New Jersey waterway using congener and homologue data: The National Oceanic and Atmospheric Administration estimate of the PCB total based on 18 congeners sigma dioxin-like congeners, an estimate of the PCB total from 38 analyzed congeners--sigma dioxin-like congeners, and the total of nine homologue groups--sigma dioxin-like congeners. These three approaches yielded similar estimates of the total nondioxin-like PCBs for a variety of fish species, whereas the totals quantified as Aroclor 1248, 1254, or 1260 were typically more than fivefold lower. Based on these results, the selection of the PCB analytical endpoints obtained from field investigations of fish and shellfish should be guided by the appropriate risk assessment methodology and by the analytical limitations.

Potential long-term ecological impacts caused by disturbance of contaminated sediments:a case study.

Several submerged barges were recently removed from the Passaic River, New Jersey, USA, in two areas (areas 1 and 2) where contaminated sediments are known to exist. During removal of the single barge in area 1, elevated turbidity levels and chemical parameters were measured. Greater increases were measured in area 2, where several barges were removed. In both areas, water column concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and several metals exceeded one or more water quality criteria; turbidity levels in area 2 also exceeded regulatory criteria. Potential chemical bioaccumulation from the water column into residential aquatic receptors was estimated using standard models and assumptions. The modeled results predicted that steady-state tissue concentrations of bioaccumulative chemicals would not occur as a result of the brief increase in water column concentrations that occurred during barge removal but that metals and PCDD/Fs could bioaccumulate to levels that exceed regulatory ecological criteria during long-term sediment disturbance activities. In addition, based on some simplistic assumptions regarding settling of suspended sediments, we estimate that chemical bioaccumulation from surface sediments into the food web could result in substantial increases in PCDD/F body burdens in the benthic forage fish, mummichog. Our findings are consistent with the limited number of field studies that have measured increased body burdens of bioaccumulative chemicals following dredging. We suggest that, prior to consideration of extensive dredging as a remedial alternative for any river system, the potential significant and long-term impacts on the food web must be evaluated.