Tag Archives: risk assessment

Biologically based models unfit for perchlorate risk assessment

Clewell HH 3rd, Gentry PR, Hack CE, Greene T, Clewell RA. An evaluation of the USEPA Proposed Approaches for applying a biologically based dose-response model in a risk assessment for perchlorate in drinking water. Regulatory toxicology and pharmacology. 2019 Jan 29. pii: S0273-2300(19)30036-4. doi: 10.1016/j.yrtph.2019.01.028.

The United States Environmental Protection Agency’s (USEPA) 2017 report, “Draft Report: Proposed Approaches to Inform the Derivation of a Maximum Contaminant Level Goal for Perchlorate in Drinking Water”, proposes novel approaches for deriving a Maximum Contaminant Level Goal (MCLG) for perchlorate using a biologically-based dose-response (BBDR) model. The USEPA (2017) BBDR model extends previously peer-reviewed perchlorate models to describe the relationship between perchlorate exposure and thyroid hormone levels during early pregnancy. Our evaluation focuses on two key elements of the USEPA (2017) report: the plausibility of BBDR model revisions to describe control of thyroid hormone production in early pregnancy and the basis for linking BBDR model results to neurodevelopmental outcomes. While the USEPA (2017) BBDR model represents a valuable research tool, the lack of supporting data for many of the model assumptions and parameters calls into question the fitness of the extended BBDR model to support quantitative analyses for regulatory decisions on perchlorate in drinking water. Until more data can be developed to address uncertainties in the current BBDR model, USEPA should continue to rely on the RfD recommended by the NAS (USEPA, 2005) when considering further regulatory action.

Dose-response meta-analysis of lung cancer risk and inorganic arsenic

Yuan T, Zhang H, Chen B, Zhang H, Tao S. Association between lung cancer risk and inorganic arsenic concentration in drinking water: a dose-response meta-analysis. Toxicol Res (Camb). 2018 Sep 18;7(6):1257-1266. doi: 10.1039/c8tx00177d.

High dose arsenic in drinking water (≥100 μg L-1) is known to induce lung cancer, but lung cancer risks at low to moderate arsenic levels and its dose-response relationship remains inconclusive. We conducted a systematic review of cohort and case-control studies that quantitatively reported the association between arsenic concentrations in drinking water and lung cancer risks by searching the PubMed database till June 14, 2018. Pooled relative risks (RRs) of lung cancer associated with full range (10 μg L-1-1000 μg L-1) and low to moderate range (<100 μg L-1) of water arsenic concentrations were calculated using random-effects models. A dose-response meta-analysis was performed to estimate the pooled associations between restricted cubic splines of log-transformed water arsenic and the lung cancer risks. Fifteen studies (9 case-control and 6 cohort studies) involving a total of 218 481 participants met the inclusion criteria. Meta-analysis identified significantly increased risks of lung cancer on exposure to both full range (RR = 1.21; 95% confidence interval [CI] = 1.05-1.37; heterogeneity I 2 = 54.3%) and low to moderate range (RR = 1.18; 95%CI = 1.00-1.35; I 2 = 56.3%) of arsenic-containing water. In the dose-response meta-analysis of eight case-control studies, we found no evidence of non-linearity, although statistical power was limited. The corresponding pooled RRs and their 95%CIs for exposure to 10 μg L-1, 50 μg L-1, and 100 μg L-1 water arsenic were 1.02 (1.00-1.03), 1.10 (1.04-1.15), and 1.20 (1.08-1.32), respectively. We provide evidence on the association between increased lung cancer risks and inorganic arsenic in drinking water across low, moderate and high levels. Minimizing arsenic levels in drinking water may be of public health importance.

Brewed tea a significant source of trihalomethane exposure

Fakour H, Lo SL. Formation and risk assessment of trihalomethanes through different tea brewing habits. Int J Hyg Environ Health. 2018 Sep 1. pii: S1438-4639(18)30193-7. doi: 10.1016/j.ijheh.2018.08.013.

Trihalomethanes (THMs) are suspected carcinogens and reproductive toxicants commonly found in chlorinated drinking water. This study investigates the formation of THMs and their associated risks during different tea brewing habits. Three main categories of tea (black, oolong, and green) under various brewing conditions and drinking water sources were tested. Tea samples prepared in ordinary thermos flask formed significant levels of total THM (TTHM). The highest TTHM formation came from black tea made with tap water, plausibly due to higher concentrations of reactive THM precursors. Compared with tap water, when the background solution is bottled water or distilled water, less TTHM was observed in prepared tea infusions. The results also revealed that unlike the traditional teapot-based tea serving habit, the removal of THMs is significantly reduced when tea infusion is stored in enclosed containers. Risk assessment analysis based on the survey among tea shop costumers also revealed that cancer risks induced by ingestion of THMs through drinking tea infusions prepared in thermos flask exceeded the tolerable level. Data obtained in this research demonstrated that drinking tea infusions directly from enclosed containers can be a significant source of exposure to THMs.

Susceptibility differs to the toxic effects of arsenic

Brenda C. Minatel1, Adam P. Sage1, Christine Anderson, Roland Hubaux, Erin A. Marshall, Wan L. Lam, Victor D. Martinez. Environmental arsenic exposure: From genetic susceptibility to pathogenesis. Environment International Volume 112, March 2018, Pages 183–197

More than 200 million people in 70 countries are exposed to arsenic through drinking water. Chronic exposure to this metalloid has been associated with the onset of many diseases, including cancer. Epidemiological evidence supports its carcinogenic potential, however, detailed molecular mechanisms remain to be elucidated. Despite the global magnitude of this problem, not all individuals face the same risk. Susceptibility to the toxic effects of arsenic is influenced by alterations in genes involved in arsenic metabolism, as well as biological factors, such as age, gender and nutrition. Moreover, chronic arsenic exposure results in several genotoxic and epigenetic alterations tightly associated with the arsenic biotransformation process, resulting in an increased cancer risk. In this review, we: 1) review the roles of inter-individual DNA-level variations influencing the susceptibility to arsenic-induced carcinogenesis; 2) discuss the contribution of arsenic biotransformation to cancer initiation; 3) provide insights into emerging research areas and the challenges in the field; and 4) compile a resource of publicly available arsenic-related DNA-level variations, transcriptome and methylation data. Understanding the molecular mechanisms of arsenic exposure and its subsequent health effects will support efforts to reduce the worldwide health burden and encourage the development of strategies for managing arsenic-related diseases in the era of personalized medicine.

Evidence lacking for low-exposure adverse effects of arsenic

Hong YS, Ye BJ, Kim YM, Kim BG, Kang GH, Kim JJ, Song KH, Kim YH, Seo JW. Investigation of Health Effects According to the Exposure of Low Concentration Arsenic Contaminated Ground Water. International journal of environmental research and public health. 2017 Nov 27;14(12). pii: E1461. doi: 10.3390/ijerph14121461.

Recent epidemiological studies have reported adverse health effects, including skin cancer, due to low concentrations of arsenic via drinking water. We conducted a study to assess whether low arsenic contaminated ground water affected health of the residents who consumed it. For precise biomonitoring results, the inorganic (trivalent arsenite (As III) and pentavalent arsenate (As V)) and organic forms (monomethylarsonate (MMA) and dimethylarsinate (DMA)) of arsenic were separately quantified by combining high-performance liquid chromatography and inductively coupled plasma mass spectroscopy from urine samples. In conclusion, urinary As III, As V, MMA, and hair arsenic concentrations were significantly higher in residents who consumed arsenic contaminated ground water than control participants who consumed tap water. But, most health screening results did not show a statistically significant difference between exposed and control subjects. We presume that the elevated arsenic concentrations may not be sufficient to cause detectable health effects. Consumption of arsenic contaminated ground water could result in elevated urinary organic and inorganic arsenic concentrations. We recommend immediate discontinuation of ground water supply in this area for the safety of the residents.

IARC Corruption Should be Rooted Out as Condition of Further US Support

Regardless of what one thinks about glyphosate, IARC corruption of science and regulatory policy decision-making must be rooted out.

“Not surprisingly, the agency branded glyphosate carcinogenic. But this time evidence is surfacing of collusion with anti-chemical activist groups and class action lawyers, serious conflicts of interest involving a key IARC glyphosate reviewer, and IARC manipulation of scientific reports along with deliberate withholding of studies that concluded the chemical is safe, so that the agency could get a guilty verdict.” click here

Another Ecologic Study on Arsenic and Bladder Cancer of Limited Utility

Ecologic studies such as this are not very informative because of limited exposure assessments. But they can certainly generate alarm. Even so, small associations such as this are questionable regardless of precise mathematical computations. Note the absence of confidence intervals on the estimates which sends a strong message to ignore the study altogether.

Saint-Jacques N, Brown P, Nauta L, Boxall J, Parker L, Dummer TJB. Estimating the risk of bladder and kidney cancer from exposure to low-levels of arsenic in drinking water, Nova Scotia, Canada. Environment international. 2017 Oct 28. pii: S0160-4120(17)31385-5. doi: 10.1016/j.envint.2017.10.014.

Arsenic in drinking water impacts health. Highest levels of arsenic have been historically observed in Taiwan and Bangladesh but the contaminant has been affecting the health of people globally. Strong associations have been confirmed between exposure to high-levels of arsenic in drinking water and a wide range of diseases, including cancer. However, at lower levels of exposure, especially near the current World Health Organization regulatory limit (10μg/L), this association is inconsistent as the effects are mostly extrapolated from high exposure studies. This ecological study used Bayesian inference to model the relative risk of bladder and kidney cancer at these lower concentrations-0-2μg/L; 2-5μg/L and; ≥5μg/L of arsenic-in 864 bladder and 525 kidney cancers diagnosed in the study area, Nova Scotia, Canada between 1998 and 2010. The model included proxy measures of lifestyle (e.g. smoking) and accounted for spatial dependencies. Overall, bladder cancer risk was 16% (2-5μg/L) and 18% (≥5μg/L) greater than that of the referent group (<2μg/L), with posterior probabilities of 88% and 93% for these risks being above 1. Effect sizes for kidney cancer were 5% (2-5μg/L) and 14% (≥5μg/L) above that of the referent group (<2μg/L), with probabilities of 61% and 84%. High-risk areas were common in southwestern areas, where higher arsenic-levels are associated with the local geology. The study suggests an increased bladder cancer, and potentially kidney cancer, risk from exposure to drinking water arsenic-levels within the current the World Health Organization maximum acceptable concentration.