Occupational exposure to antimony trioxide: a risk assessment.

OBJECTIVES: The US National Toxicology Program (NTP) recently recommended in its Report on Carcinogens Monograph for Antimony Trioxide that antimony trioxide be listed as 'reasonably anticipated to be a human carcinogen' based on sufficient evidence of carcinogenicity in experimental animals and supporting evidence from mechanistic studies. Our goal was to estimate the possible human cancer risk from occupational exposure to antimony trioxide. METHODS: We selected data from 2-year inhalation studies in male and female mice conducted by the NTP and performed cancer dose-response analyses using cancer models and benchmark dose methods developed by the US Environmental Protection Agency. In these analyses, we generated benchmark doses and cancer slope factors for antimony trioxide, and then estimated human cancer risk under various exposure scenarios. Typical and worst-case inhalation scenarios in multiple occupational settings were used in risk estimation. RESULTS: In typical case scenarios, the occupational cancer risk from antimony trioxide was estimated to be 0.025 (25 in 1000) for persons working with flame retardants in plastics and textiles for 40 years. Under worst-case scenarios, the occupational cancer risk was estimated to be 0.11 (110 in 1000) for persons working with flame retardants in plastics and textiles. At the current Occupational Safety and Health Administration Permissible Exposure Limit, the cancer risk for occupational inhalation exposure of antimony trioxide was estimated to be 0.096 (96 in 1000). CONCLUSION: The risk estimates calculated in this study suggest that exposure to antimony trioxide at levels present in certain occupational settings results in a large increase in the risk of developing cancer.

Proposed Key Characteristics of Female Reproductive Toxicants as an Approach for Organizing and Evaluating Mechanistic Data in Hazard Assessment.

BACKGROUND: Identification of female reproductive toxicants is currently based largely on integrated epidemiological and in vivo toxicology data and, to a lesser degree, on mechanistic data. A uniform approach to systematically search, organize, integrate, and evaluate mechanistic evidence of female reproductive toxicity from various data types is lacking. OBJECTIVE: We sought to apply a key characteristics approach similar to that pioneered for carcinogen hazard identification to female reproductive toxicant hazard identification. METHODS: A working group of international experts was convened to discuss mechanisms associated with chemical-induced female reproductive toxicity and identified 10 key characteristics of chemicals that cause female reproductive toxicity: 1) alters hormone receptor signaling; alters reproductive hormone production, secretion, or metabolism; 2) chemical or metabolite is genotoxic; 3) induces epigenetic alterations; 4) causes mitochondrial dysfunction; 5) induces oxidative stress; 6) alters immune function; 7) alters cell signal transduction; 8) alters direct cell­cell interactions; 9) alters survival, proliferation, cell death, or metabolic pathways; and 10) alters microtubules and associated structures. As proof of principle, cyclophosphamide and diethylstilbestrol (DES), for which both human and animal studies have demonstrated female reproductive toxicity, display at least 5 and 3 key characteristics, respectively. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), for which the epidemiological evidence is mixed, exhibits 5 key characteristics. DISCUSSION: Future efforts should focus on evaluating the proposed key characteristics against additional known and suspected female reproductive toxicants. Chemicals that exhibit one or more of the key characteristics could be prioritized for additional evaluation and testing. A key characteristics approach has the potential to integrate with pathway-based toxicity testing to improve prediction of female reproductive toxicity in chemicals and potentially prevent some toxicants from entering common use. https://doi.org/10.1289/EHP4971.

Assessment of the Endocrine-Disrupting Effects of Trichloroethylene and Its Metabolites Using in Vitro and in Silico Approaches.

Trichloroethylene (TCE) is a ubiquitous environmental contaminant, which may have effects on both ecosystem and human health. TCE has been reported to cause several toxic effects, but little effort has been made to assess the ecological risks of TCE or its major metabolites: trichloroethanol (TCOH), trichloroacetic acid, and oxalic acid (OA). In this study, the endocrine-disrupting potential of TCE and its metabolites were investigated using in vitro and in silico approaches. We examined alterations in the steroidogenesis pathway using the NCI-H295R cell line and utilized receptor-mediated luciferase reporter cell lines to identify effects on estrogen and androgen receptors. Molecular docking was also used to explore chemical interactions with these receptors. All test chemicals except OA significantly increased 17ß-estradiol production which can be attributed to an up-regulation of 17ß-hydroxysteroid dehydrogenase. Moreover, TCOH exhibited significant antiestrogenic activity with a RIC20 (20% relative inhibitory concentration) of 3.7 × 10-7 M. Molecular docking simulation supported this finding with lower docking scores for TCOH, indicating that hydrogen bonds may stabilize the interaction between TCOH and the estrogen receptor binding pocket. These findings suggest that TCE contamination poses an endocrine-disrupting threat, which has implications for both ecological and human health.

Marine ecological risk assessment methods for radiation accidents.

Ecological risk assessment (ERA) is a powerful technical tool that can be used to analyze potential and extreme adverse environmental impacts. With the rapid development of nuclear power plants in coastal areas around the world, the establishment of approaches and methodologies for marine ERA with a focus on radiation accidents is an urgent requirement for marine environmental management. In this study, the approaches and methodologies for ERA pertaining to marine radiation accidents (MRA) are discussed and summarized with applications in case studies, such as the nuclear accident in Fukushima, Japan, and a hypothetical accident in Daya Bay, China. The concepts of ERA and Risk Degree of ERA on MRA are defined for the first time to optimize the ERA system. The results of case studies show that the ERA approach and methodology for MRA are scientifically sound and effective in both the early and late stage of MRAs along with classic ERA Approach and the ERICA Integrated Approach. The results can be useful in the decision-making processes and the risk management at the beginning of accident as well as the ecological restoration after the accident.

Trade-off between water pollution prevention, agriculture profit, and farmer practice--an optimization methodology for discussion on land-use adjustment in China.

Agricultural decision-making to control nonpoint source (NPS) water pollution may not be efficiently implemented, if there is no appropriate cost-benefit analysis on agricultural management practices. This paper presents an interval-fuzzy linear programming (IFLP) model to deal with the trade-off between agricultural revenue, NPS pollution control, and alternative practices through land adjustment for Wuchuan catchment, a typical agricultural area in Jiulong River watershed, Fujian Province of China. From the results, the lower combination of practice 1, practice 2, practice 3, and practice 7 with the land area of 12.6, 5.2, 145.2, and 85.3 hm(2), respectively, could reduce NPS pollution load by 10%. The combination yields an income of 98,580 Chinese Yuan/a. If the pollution reduction is 15%, the higher combination need practice 1, practice 2, practice 3, practice 5, and practice 7 with the land area of 54.4, 23.6, 18.0, 6.3, and 85.3 hm(2), respectively. The income of this combination is 915,170 Chinese Yuan/a. The sensitivity analysis of IFLP indicates that the cost-effective practices are ranked as follows: practice 7 > practice 2 > practice 1 > practice 5 > practice 3 > practice 6 > practice 4. In addition, the uncertainties in the agriculture NPS pollution control system could be effectively quantified by the IFLP model. Furthermore, to accomplish a reasonable and applicable project of land-use adjustment, decision-makers could also integrate above solutions with their own experience and other information.

Water quality and non-point sources of risk: the Jiulong River Watershed, P. R. of China.

Retrospective water quality assessment plays an essential role in identifying trends and causal associations between exposures and risks, thus it can be a guide for water resources management. We have developed empirical relationships between several time-varying social and economic factors of economic development, water quality variables such as nitrate-nitrogen, COD(Mn), BOD(5), and DO, in the Jiulong River Watershed and its main tributary, the West River. Our analyses used alternative statistical methods to reduce the dimensionality of the analysis first and then strengthen the study's causal associations. The statistical methods included: factor analysis (FA), trend analysis, Monte Carlo/bootstrap simulations, robust regressions and a coupled equations model, integrated into a framework that allows an investigation and resolution of the issues that may affect the estimated results. After resolving these, we found that the concentrations of nitrogen compounds increased over time in the West River region, and that fertilizer used in agricultural fruit crops was the main risk with regard to nitrogen pollution. The relationships we developed can identify hazards and explain the impact of sources of different types of pollution, such as urbanization, and agriculture.

Current understanding of the mechanism of benzene-induced leukemia in humans: implications for risk assessment.

Benzene causes acute myeloid leukemia and probably other hematological malignancies. As benzene also causes hematotoxicity even in workers exposed to levels below the US permissible occupational exposure limit of 1 part per million, further assessment of the health risks associated with its exposure, particularly at low levels, is needed. Here, we describe the probable mechanism by which benzene induces leukemia involving the targeting of critical genes and pathways through the induction of genetic, chromosomal or epigenetic abnormalities and genomic instability, in a hematopoietic stem cell (HSC); stromal cell dysregulation; apoptosis of HSCs and stromal cells and altered proliferation and differentiation of HSCs. These effects modulated by benzene-induced oxidative stress, aryl hydrocarbon receptor dysregulation and reduced immunosurveillance, lead to the generation of leukemic stem cells and subsequent clonal evolution to leukemia. A mode of action (MOA) approach to the risk assessment of benzene was recently proposed. This approach is limited, however, by the challenges of defining a simple stochastic MOA of benzene-induced leukemogenesis and of identifying relevant and quantifiable parameters associated with potential key events. An alternative risk assessment approach is the application of toxicogenomics and systems biology in human populations, animals and in vitro models of the HSC stem cell niche, exposed to a range of levels of benzene. These approaches will inform our understanding of the mechanisms of benzene toxicity and identify additional biomarkers of exposure, early effect and susceptibility useful for risk assessment.

Toxicogenomic profiling of chemically exposed humans in risk assessment.

Gene-environment interactions contribute to complex disease development. The environmental contribution, in particular low-level and prevalent environmental exposures, may constitute much of the risk and contribute substantially to disease. Systematic risk evaluation of the majority of human chemical exposures, has not been conducted and is a goal of regulatory agencies in the U.S. and worldwide. With the recent recognition that toxicological approaches more predictive of effects in humans are required for risk assessment, in vitro human cell line data as well as animal data are being used to identify toxicity mechanisms that can be translated into biomarkers relevant to human exposure studies. In this review, we discuss how data from toxicogenomic studies of exposed human populations can inform risk assessment, by generating biomarkers of exposure, early effect, and/or susceptibility, elucidating mechanisms of action underlying exposure-related disease, and detecting response at low doses. Good experimental design incorporating precise, individual exposure measurements, phenotypic anchors (pre-disease or traditional toxicological markers), and a range of relevant exposure levels, is necessary. Further, toxicogenomic studies need to be designed with sufficient power to detect true effects of the exposure. As more studies are performed and incorporated into databases such as the Comparative Toxicogenomics Database (CTD) and Chemical Effects in Biological Systems (CEBS), data can be mined for classification of newly tested chemicals (hazard identification), and, for investigating the dose-response, and inter-relationship among genes, environment and disease in a systems biology approach (risk characterization).

Formaldehyde and leukemia: epidemiology, potential mechanisms, and implications for risk assessment.

Formaldehyde is widely used in the United States and other countries. Occupational and environmental exposures to formaldehyde may be associated with an increased risk of leukemia in exposed individuals. However, risk assessment of formaldehyde and leukemia has been challenging due to inconsistencies in human and animal studies and the lack of a known mechanism for leukemia induction. Here, we provide a summary of the symposium at the Environmental Mutagen Society Meeting in 2008, which focused on the epidemiology of formaldehyde and leukemia, potential mechanisms, and implication for risk assessment, with emphasis on future directions in multidisciplinary formaldehyde research. Updated results of two of the three largest industrial cohort studies of formaldehyde-exposed workers have shown positive associations with leukemia, particularly myeloid leukemia, and a recent meta-analysis of studies to date supports this association. Recent mechanistic studies have shown the formation of formaldehyde-induced DNA adducts and characterized the essential DNA repair pathways that mitigate formaldehyde toxicity. The implications of the updated findings for the design of future studies to more effectively assess the risk of leukemia arising from formaldehyde exposure were discussed and specific recommendations were made. A toxicogenomic approach in experimental models and human exposure studies, together with the measurement of biomarkers of internal exposure, such as formaldehyde-DNA and protein adducts, should prove fruitful. It was recognized that increased communication among scientists who perform epidemiology, toxicology, biology, and risk assessment could enhance the design of future studies, which could ultimately reduce uncertainty in the risk assessment of formaldehyde and leukemia.

Formaldehyde in China: production, consumption, exposure levels, and health effects.

Formaldehyde, an economically important chemical, is classified as a human carcinogen that causes nasopharyngeal cancer and probably leukemia. As China is the largest producer and consumer of formaldehyde in the world, the Chinese population is potentially at increased risk for cancer and other associated health effects. In this paper we review formaldehyde production, consumption, exposure, and health effects in China. We collected and analyzed over 200 Chinese and English documents from scientific journals, selected newspapers, government publications, and websites pertaining to formaldehyde and its subsequent health effects. Over the last 20 years, China's formaldehyde industry has experienced unprecedented growth, and now produces and consumes one-third of the world's formaldehyde. More than 65% of the Chinese formaldehyde output is used to produce resins mainly found in wood products - the major source of indoor pollution in China. Although the Chinese government has issued a series of standards to regulate formaldehyde exposure, concentrations in homes, office buildings, workshops, public places, and food often exceed the national standards. In addition, there have been numerous reports of formaldehyde-induced health problems, including poisoning and cancer. The lack of quality epidemiological studies and basic data on exposed populations emphasizes the need for more extensive studies on formaldehyde and its related health effects in China.

Heavy metal contamination in western Xiamen Bay sediments and its vicinity, China.

Concentrations of selected heavy metals (Cu, Pb, Zn, Cd, Cr, Ni and Fe) in surface sediments from nine sites in western Xiamen Bay and its vicinity were studied in order to understand current metal contamination due to urbanization and economic development in Xiamen, China. The sediment samples were collected in December 2004 and July 2005 respectively in order to examine temporal variations. In this study, we found that heavy metal concentrations in surface sediments sampled in the western Xiamen Bay and adjacent Maluan Bay and Yuandang Lagoon varied from 19 to 97mg kg(-1) for Cu, 45 to 60mg kg(-1) for Pb, 65 to 223mg kg(-1) for Zn, 0.11 to 1.01mg kg(-1) for Cd, 37 to 134mg kg(-1) for Cr, 25 to 65mg kg(-1) for Ni and 3.08 to 4.81% for Fe. Although all metal concentrations in sediments meets Chinese National Standard Criteria for Marine Sediment Quality, both metal enrichment factors (EF) and geoaccumulation index (I(geo)) show that Pb contamination exists in the entire study area and contamination of other metals are also present in some locations depending on the sources, of which sewage outlets and commercial ports are the main sources of contaminants to the area. This study shows that using the sediment quality standard criteria only to assess sediments cannot properly reflect sediment contamination. A multiple approaches should be applied for the sediment quality assessment.

Assessment of dermal exposure to benzene and toluene in shoe manufacturing by activated carbon cloth patches.

OBJECTIVES: The aim of this investigation was to use activated carbon cloth (ACC) patches to study the probability and extent of dermal exposure to benzene and toluene in a shoe factory. METHODS: Inhalation and dermal exposure loading were measured simultaneously in 70 subjects on multiple days resulting in 113 observations. Dermal exposure loading was assessed by ACC patches attached to likely exposed skin areas (e.g. the palm of the hand and abdomen). A control patch at the chest and an organic vapor monitor (OVM) were used to adjust the hand and abdomen patches for the contribution from the air through passive absorption of benzene and toluene on the ACC patches. Systemic exposure was assessed by quantification of unmetabolized benzene (UBz) and toluene (UTol) in urine. RESULTS: Mean air concentrations for the study population were 1.5 and 7.5 ppm for benzene and toluene, respectively. Iterative regression analyses between the control patch, OVM and the dermal patches showed that only a small proportion of the ACC patches at the hand had likely benzene (n = 4; mean 133 microg cm(-2) h(-1)) or toluene (n = 5; mean 256 microg cm(-2) h(-1)) contamination. Positive patches were exclusively observed among subjects performing the task of gluing. Significant dermal exposure loading to the abdomen was detected only for toluene (n = 2; mean 235 microg cm(-2) h(-1)). No relation was found between having a positive hand or abdomen ACC patch and UBz or UTol levels. In contrast a strong association was found between air levels of benzene (p = 0.0016) and toluene (p < 0.0001) and their respective urinary levels. CONCLUSIONS: ACC patches are shown to be a useful technique for quantifying the probability of dermal exposure to organic solvents and to provide estimates of the potential contribution of the dermal pathway to systemic exposure. Using ACC patches we show that dermal exposure to benzene and toluene in a shoe manufacturing factory is probably rare, and when it occurred exposures were relatively low and did not significantly contribute to systemic exposure.

Persistent organochlorine pollutants in surface sediments and economic shellfish of Minjiang Estuary-Mazu and Xiamen-Jinmen sea areas.

Samples of surface sediment and shellfish were collected from Minjiang Estuary-Mazu and Xiamen-Jinmen sea areas and were analyzed for hexachlorocyclohexanes (HCHs), dichlorodiphenyl-trichlorophenyl (DDT) and its degraded derivatives dichloro-diphenyl-dichloroethane (DDT) and dichloro-dichlorophenyl-ethylene (DDE), and polychlorinated biphenyls (PCBs) by gas chromatography. Concentration ranges of HCHs, DDTs, and PCBs in the sediments were 0.03-0.48, 1.10-14.3, and ND to 0.76 ng/g dw, respectively; those for shellfish samples were ND to 1.5, 21.5-892, dw and ND-3.7 ng/g dw, respectively. The results showed that the concentrations of such oganochlorine compounds (OCs) in the sediments were usually low as compared with other sea areas and estuaries, and the organochlorines were accumulated in marine bivalve mollusks, particularly in oyster. With respect to the concentrations of HCHs, DDTs, and PCBs in the samples of either sediment or shellfish, DDTs were higher than HCHs and PCBs. The concentrations of OCs in shellfish samples varied with the sampling locations and organism species but were generally higher than those in the sediments. The concentration distributions, compositions, and residue levels of these OCs are extensively discussed and evaluated.

Detailed exposure assessment for a molecular epidemiology study of benzene in two shoe factories in China.

OBJECTIVES: We carried out a detailed exposure assessment of benzene and toluene in two shoe factories in Tianjin, China. Our goal was to identify workers with a broad range of benzene exposures, for an epidemiologic study relating exposure to early biologic effects. METHODS: A comprehensive exposure survey program was initiated. Over a period of 16 months, 2783 personal solvent exposure samples were collected in two workplaces from 250 workers. Mixed-effects models were used to identify factors affecting exposure. Principal component analyses (PCA) and subsequent regression analyses on the scores of the identified principal components were used to relate potential co-exposures to various exposure sources present in the workplace. RESULTS: The mean benzene exposure level was 21.86 p.p.m. (10th-90th percentiles 5.23-50.63 p.p.m.) in the smaller shoe factory (factory A) and 3.46 p.p.m. (10th-90th percentiles 0.20-7.00 p.p.m.) in the larger shoe factory (factory B). Within-factory exposure levels differed among job titles and were higher for subjects directly involved in handling glues. In contrast, mean toluene levels were relatively similar in the two factories (factory A, 9.52 p.p.m.; factory B, 15.88 p.p.m.). A seasonal trend was identified for both benzene and toluene in factory B. This could be explained in part by changes in air movement and ventilation patterns occurring during the year. A seasonal trend was not present in the smaller shoe factory, where general ventilation was absent. Supplemental analysis showed that exposure levels to other hydrocarbons were low (< or =5 p.p.m.), less than 5% of their respective ACGIH threshold limit values, and generally comparable in the two factories. PCA showed that co-exposures in factory B could largely be explained by glue sources that were used in distinct areas in the workplace. CONCLUSIONS: We demonstrated the occurrence of a broad range of benzene exposure levels in two shoe manufacturing factories in Tianjin, China. Benzene and toluene exposures were determined in part by the degree of contact with glues, the benzene and toluene content of each glue, air movement and ventilation patterns. The availability of long-term monthly personal monitoring data provides an excellent opportunity to estimate individual exposures at different times during the 1 yr period of observation.

Environmental risk assessment of pesticides on aquatic life in Xiamen, China.

This paper describes the results of the environmental risk assessment of the pesticides used in agriculture in Xiamen, China. The goal was to assess the impact on water resources, particularly on fisheries and mariculture. Data on ecotoxicological properties of the pesticides and their physico-chemical profile were collected. The simulation of the environmental behaviour of the pesticides in relation to the load applied onto the agricultural areas was done using the SoilFug model. Risk assessment was performed, pesticides approximate concentrations have been calculated, chemicals at highest risk were identified, and risk management measures were indicated. This study could represent a cost-effective method that may be used before engaging in expensive monitoring programs for pesticide use in developing countries, where analytical facilities are lacking.