Chromium VI and stomach cancer: a meta-analysis of the current epidemiological evidence.

OBJECTIVES: Chromium VI (hexavalent chromium, Cr(VI)) is an established cause of lung cancer, but its association with gastrointestinal cancer is less clear. The goal of this study was to examine whether the current human epidemiological research on occupationally inhaled Cr(VI) supports the hypothesis that Cr(VI) is associated with human stomach cancer. METHODS: Following a thorough literature search and review of individual studies, we used meta-analysis to summarise the current epidemiological literature on inhaled Cr(VI) and stomach cancer, explore major sources of heterogeneity, and assess other elements of causal inference. RESULTS: We identified 56 cohort and case-control studies and 74 individual relative risk (RR) estimates on stomach cancer and Cr(VI) exposure or work in an occupation associated with high Cr(VI) exposure including chromium production, chrome plating, leather work and work with Portland cement. The summary RR for all studies combined was 1.27 (95% CI 1.18 to 1.38). In analyses limited to only those studies identifying increased risks of lung cancer, the summary RR for stomach cancer was higher (RR=1.41, 95% CI 1.18 to 1.69). CONCLUSIONS: Overall, these results suggest that Cr(VI) is a stomach carcinogen in humans, which is consistent with the tumour results reported in rodent studies.

Methodological considerations in screening for cumulative environmental health impacts: lessons learned from a pilot study in California.

Polluting facilities and hazardous sites are often concentrated in low-income communities of color already facing additional stressors to their health. The influence of socioeconomic status is not considered in traditional models of risk assessment. We describe a pilot study of a screening method that considers both pollution burden and population characteristics in assessing the potential for cumulative impacts. The goal is to identify communities that warrant further attention and to thereby provide actionable guidance to decision- and policy-makers in achieving environmental justice. The method uses indicators related to five components to develop a relative cumulative impact score for use in comparing communities: exposures, public health effects, environmental effects, sensitive populations and socioeconomic factors. Here, we describe several methodological considerations in combining disparate data sources and report on the results of sensitivity analyses meant to guide future improvements in cumulative impact assessments. We discuss criteria for the selection of appropriate indicators, correlations between them, and consider data quality and the influence of choices regarding model structure. We conclude that the results of this model are largely robust to changes in model structure.

A screening method for assessing cumulative impacts.

The California Environmental Protection Agency (Cal/EPA) Environmental Justice Action Plan calls for guidelines for evaluating "cumulative impacts." As a first step toward such guidelines, a screening methodology for assessing cumulative impacts in communities was developed. The method, presented here, is based on the working definition of cumulative impacts adopted by Cal/EPA: "Cumulative impacts means exposures, public health or environmental effects from the combined emissions and discharges in a geographic area, including environmental pollution from all sources, whether single or multi-media, routinely, accidentally, or otherwise released. Impacts will take into account sensitive populations and socio-economic factors, where applicable and to the extent data are available." The screening methodology is built on this definition as well as current scientific understanding of environmental pollution and its adverse impacts on health, including the influence of both intrinsic, biological factors and non-intrinsic socioeconomic factors in mediating the effects of pollutant exposures. It addresses disparities in the distribution of pollution and health outcomes. The methodology provides a science-based tool to screen places for relative cumulative impacts, incorporating both the pollution burden on a community- including exposures to pollutants, their public health and environmental effects- and community characteristics, specifically sensitivity and socioeconomic factors. The screening methodology provides relative rankings to distinguish more highly impacted communities from less impacted ones. It may also help identify which factors are the greatest contributors to a community's cumulative impact. It is not designed to provide quantitative estimates of community-level health impacts. A pilot screening analysis is presented here to illustrate the application of this methodology. Once guidelines are adopted, the methodology can serve as a screening tool to help Cal/EPA programs prioritize their activities and target those communities with the greatest cumulative impacts.

Bisphenol A: developmental toxicity from early prenatal exposure.

Bisphenol A (BPA) exposure has been documented in pregnant women, but consequences for development are not yet widely studied in human populations. This review presents research on the consequences for offspring of BPA exposure during pregnancy. Extensive work in laboratory rodents has evaluated survival and growth of the conceptus, interference with embryonic programs of development, morphological sex differentiation, sex differentiation of the brain and behavior, immune responsiveness, and mechanism of action. Sensitive measures include RAR, aryl hydrocarbon receptor, and Hox A10 gene expression, anogenital distance, sex differentiation of affective and exploratory behavior, and immune hyperresponsiveness. Many BPA effects are reported at low doses (10-50 µg/kg d range) by the oral route of administration. At high doses (>500,000 µg/kg d) fetal viability is compromised. Much of the work has centered around the implications of the estrogenic actions of this agent. Some work related to thyroid mechanism of action has also been explored. BPA research has actively integrated current knowledge of developmental biology, concepts of endocrine disruption, and toxicological research to provide a basis for human health risk assessment.

Beyond risk assessment: principles for assessing community impacts.

Risk assessment methods have evolved over time to become better at evaluating risks associated with single chemical exposures, yet are limited in evaluating risks faced by communities with exposures to a range of chemical hazards via multiple routes. Recognizing the need to identify better approaches to assess disparate impacts facing certain populations due to environmental pollution, the authors evaluated activities within the Office of Environmental Health Hazard Assessment (in California's Environmental Protection Agency) that had begun addressing these concerns by moving beyond standard risk assessment practices. On the basis of these examples, the authors identify 4 overarching principles to guide community assessments and explore how their application can improve these assessments. More work is needed in several areas, including developing information on exposure differences due to cultural practices, lifestyle patterns, and other factors; developing methods to recognize and take into account increased susceptibility; developing tools for assessing cumulative impacts; and improving communication with communities.

A blood lead benchmark for assessing risks from childhood lead exposure.

Lead exposure is an insidious problem, causing subtle effects in children at low exposure levels where clinical signs are not apparent. Although a target blood lead concentration (Pb(B)) of ten micrograms per deciliter (10 microg/dL) has been used as the basis for environmental decision-making in California for nearly two decades, recent epidemiologic evidence suggests a relationship between cognitive deficits and Pb(B) at concentrations < 10 microg/dL. Based on a published meta-analysis of children's IQ scores and their blood lead concentrations, we developed a new blood lead benchmark: an incremental increase in blood lead concentration (DeltaPb(B)) of 1 microg/dL, an increase that we estimate could decrease the IQ score in an average school child in California by up to one point. Although there is no evidence to date for a threshold for the neurobehavioral effects of lead, a one-point IQ decrement was chosen to represent a de minimus change. To safeguard the intellectual potential of all children, additional efforts to reduce or eliminate multiple-source exposures to lead are warranted.

Cancer mortality in a Chinese population exposed to hexavalent chromium in drinking water.

BACKGROUND: In 1987, investigators in Liaoning Province, China, reported that mortality rates for all cancer, stomach cancer, and lung cancer in 1970-1978 were higher in villages with hexavalent chromium (Cr+6)-contaminated drinking water than in the general population. The investigators reported rates, but did not report statistical measures of association or precision. METHODS: Using reports and other communications from investigators at the local Jinzhou Health and Anti-Epidemic Station, we obtained data on Cr+6 contamination of groundwater and cancer mortality in 9 study regions near a ferrochromium factory. We estimated: (1) person-years at risk in the study regions, based on census and population growth rate data, (2) mortality counts, based on estimated person-years at risk and previously reported mortality rates, and (3) rate ratios and 95% confidence intervals. RESULTS: The all-cancer mortality rate in the combined 5 study regions with Cr+6-contaminated water was negligibly elevated in comparison with the rate in the 4 combined study regions without contaminated water (rate ratio = 1.13; 95% confidence interval = 0.86-1.46), but was somewhat more elevated in comparison with the whole province (1.23; 0.97-1.53). Stomach cancer mortality in the regions with contaminated water was more substantially elevated in comparison with the regions without contaminated water (1.82; 1.11-2.91) and the whole province (1.69; 1.12-2.44). Lung cancer mortality was slightly elevated in comparison with the unexposed study regions (1.15; 0.62-2.07), and more strongly elevated in comparison with the whole province (1.78; 1.03-2.87). Mortality from other cancers combined was not elevated in comparison with either the unexposed study regions (0.86; 0.53-1.36) or the whole province (0.92; 0.58-1.38). CONCLUSIONS: While these data are limited, they are consistent with increased stomach cancer risk in a population exposed to Crz=6 in drinking water.

Evaluation and application of the RD50 for determining acceptable exposure levels of airborne sensory irritants for the general public.

BACKGROUND: The RD(50) (exposure concentration producing a 50% respiratory rate decrease) test evaluates airborne chemicals for sensory irritation and has become an American Society for Testing and Materials (ASTM) standard method. Past studies reported good correlations (R(2)) between RD(50)s and the occupational exposure limits, particularly threshold limit values (TLVs). OBJECTIVE: The main purpose of this study was to examine the relationship between RD(50)s and human sensory irritation responses in a quantitative manner, particularly for chemicals that produce burning sensation of the eyes, nose, or throat, based on lowest observed adverse effect levels (LOAELs) reported for human subjects. METHODS: We compared RD(50)s with LOAELs and acute reference exposure levels (RELs). RELs, developed by the California Environmental Protection Agency's Office of Environmental Health Hazard Assessment, represent a level at which no adverse effects are anticipated after exposure. We collected RD(50)s from the published literature and evaluated them for consistency with ASTM procedures. We identified LOAELs for human irritation and found 25 chemicals with a corresponding RD(50) in mice. DISCUSSION: We found the relationship between RD(50)s and LOAELs as log RD(50) = 1.16 (log LOAEL) + 0.77 with an R(2) value of 0.80. This strong correlation supports the use of the RD(50) in establishing exposure limits for the public. We further identified 16 chemical irritants with both RD(50)s and corresponding acute RELs, and calculated the relationship as log RD(50) = 0.71 (log REL) + 2.55 with an R(2) value of 0.71. This relationship could be used to identify health protective values for the public to prevent respiratory or sensory irritation. CONCLUSION: Consequently, we believe that the RD(50) has benefits for use in setting protective levels for the health of both workers and the general population.

Development of a health-protective drinking water level for perchlorate.

We evaluated animal and human toxicity data for perchlorate and identified reduction of thyroidal iodide uptake as the critical end point in the development of a health-protective drinking water level [also known as the public health goal (PHG)] for the chemical. This work was performed under the drinking water program of the Office of Environmental Health Hazard Assessment of the California Environmental Protection Agency. For dose-response characterization, we applied benchmark-dose modeling to human data and determined a point of departure (the 95% lower confidence limit for 5% inhibition of iodide uptake) of 0.0037 mg/kg/day. A PHG of 6 ppb was calculated by using an uncertainty factor of 10, a relative source contribution of 60%, and exposure assumptions specific to pregnant women. The California Department of Health Services will use the PHG, together with other considerations such as economic impact and engineering feasibility, to develop a California maximum contaminant level for perchlorate. We consider the PHG to be adequately protective of sensitive subpopulations, including pregnant women, their fetuses, infants, and people with hypothyroidism.

Development of a chronic inhalation reference level for respirable crystalline silica.

Chronic inhalation exposure of workers to crystalline silica can result in silicosis. The general public can also be exposed to lower levels of crystalline silica from quarries, sand blasting, and entrained fines particles from surface soil. We have derived an inhalation chronic reference exposure level for silica, a level below which no adverse effects due to prolonged exposure would be expected in the general public. Incidence of silicosis and silica exposure data from a cohort of 2235 white South African gold miners yielded a reference level of 3 microg/m3) for respirable silica (particle size as defined occupationally) using a benchmark concentration approach. Data from cohorts of American gold miners, Chinese tin miners, diatomaceous earth workers, and black South African gold miners yielded similar results with a range of 3-10 microg/m3. Strengths of the chronic reference exposure level include the availability of several large long-term studies of inhalation in workers at varying exposure concentrations, adequate histopathological and radiologic analysis, adequate follow-up of exposed workers, a dose-response effect in several studies, observation of a No Observed Adverse Effect Level in the key study, and the power of the key study to detect a small effect. Uncertainties include the general underestimation of silicosis by radiography alone and the uncertainties in exposure estimation.

Development of acute inhalation reference exposure levels (RELs) to protect the public from predictable excursions of airborne toxicants.

Uniform guidelines have been developed for the derivation of 1-h acute inhalation reference exposure levels (RELs) applicable to the general public exposed routinely to hazardous substances released into the environment. Existing acute exposure guidance values developed by other organizations have been examined, and strengths and weaknesses in these existing guidelines have been identified. The results of that examination have led to the development of a reproducible and resource-intensive methodology to calculate acute inhalation RELs for 41 prioritized chemicals. Approaches to estimating levels protective against mild and severe acute effects are discussed in this report. The default methodology is the no-observed-adverse-effect level (NOAEL)/uncertainty factor (UF) approach using mainly reports in the peer-reviewed toxicological and medical literature. For two well-studied chemicals, ammonia and formaldehyde, the data allowed a benchmark dose (or concentration) methodology, as a departure from the default options, to be used. However, better human dose-response data from, for example, improved workplace monitoring correlated with symptoms, and more extensive epidemiological studies are needed before the departure from default approaches can be expanded to more substances.

Characterization of the LOAEL-to-NOAEL uncertainty factor for mild adverse effects from acute inhalation exposures.

This analysis was undertaken to reduce uncertainty in acute inhalation risk assessment for mild acute effects. Applying uncertainty factors (UFs) to the no-observed-adverse-effect level (NOAEL) is the primary approach used in threshold-based risk assessments. When a NOAEL is unavailable, a UF of 10 is often applied to a lowest-observed-adverse-effect level (LOAEL) to estimate the NOAEL. We evaluated the LOAEL-to-NOAEL relationship for mild acute inhalation toxicity for 215 data sets for 36 hazardous air pollutants. The LOAEL-to-NOAEL ratios were 2.0, 5.0, 6.3, and 10.0 for the 50th, 90th, 95th, and 99 th percentile, respectively. The 90% confidence interval for the 95th percentile was 5.0-7.5. Consequently, based on previous dose placement practice, the LOAEL-to-NOAEL UF of 6 would be protective for 95% of the responses, and a value of 10 would be protective of 99% of the responses. The ratio values were not associated with the size of the experimental group. There was little variability among species, particularly at the median. This analysis is reflective only of mild acute inhalation toxicity. For other exposure routes, exposure durations, or more severe toxicity, the distributions are likely to be different.

Fire risk assessment and management

Approximately 18 test methods have been developed to examine the acute toxicity of thermal decomposition products produced in fires. However, the information obtained from these tests has not be integrated into a fire risk assessment. This paper presents a fire risk assessment methodology with the goal of enhancing risk management. A concentration-time product for estimating exposure was found most appropriate for comparing the toxicity of decomposition products with each other and to pure gases.(AU)