Tag Archives: health effects

Review: Hazard and mode of action of DBPs

Raquel S. Chaves, Catarina S. Vítor V. Cardoso, Maria J. Benoliel Miguel M. Santos. Hazard and mode of action of disinfection by-products (DBPs) in water for human consumption: Evidences and research priorities. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, Volume 223, September 2019, Pages 53-61

Disinfection of water system is an essential strategy to protect human health from pathogens and prevent their regrowth during water distribution, but the reaction of disinfectant agents with organic matter can lead to the formation of disinfection by-products (DBPs). Given their widespread occurrence, potential human health impacts and (eco)toxicity associated with exposure to DBPs are of particular interest due to their potential carcinogenicity and vary non-carcinogenic effects, such as endocrine disruption. Understanding the public health implications of this emerging issue is crucial for societies and decision-makers, supporting more effective water safety plans. Here, we review the recent literature on the effects of DBPs presented in drinking water and treated swimming pools water, focusing particularly in unregulated compounds and the putative underlying mode of action, linking the available data with adverse health outcomes. Overall, the majority of studies highlight the limited knowledge in the understanding of the underlying mode of action of DBPs. Yet, available evidences indicate that different signaling pathways seem to be involved in the adverse outcomes associated with distinct DBPs classes. The main knowledge gaps in this field are also identified, and future research priorities discussed.

Meta-analyses are very squishy when something is made up out of nothing

S. Stanley Young and Warren B. Kindzierski. Evaluation of a meta-analysis of air quality and heart attacks, a case studyCritical Reviews in Toxicology  https://doi.org/10.1080/10408444.2019.1576587

It is generally acknowledged that claims from observational studies often fail to replicate. An exploratory study was undertaken to assess the reliability of base studies used in meta-analysis of short-term air quality-myocardial infarction risk and to judge the reliability of statistical evidence from meta-analysis that uses data from observational studies. A highly cited meta-analysis paper examining whether short-term air quality exposure triggers myocardial infarction was evaluated as a case study. The paper considered six air quality components – carbon monoxide, nitrogen dioxide, sulphur dioxide, particulate matter 10 lm and 2.5 lm in diameter (PM10 and PM2.5), and ozone. The number of possible questions and statistical models at issue in each of 34 base papers used were estimated and p-value plots for each of the air components were constructed to evaluate the effect heterogeneity of p-values used from the base papers. Analysis search spaces (number of statistical tests possible) in the base papers were large, median 1⁄4 12,288 (interquartile range 1⁄4 2496 ” 58,368), in comparison to actual statistical test results presented. Statistical test results taken from the base papers may not provide unbiased measures of effect for meta-analysis. Shapes of p-value plots for the six air components were consistent with the possibility of analysis manipulation to obtain small p-values in several base papers. Results suggest the appearance of heterogeneous, researcher-generated p-values used in the meta-analysis rather than unbiased evidence of real effects for air quality. We conclude that this meta-analysis does not provide reliable evidence for an association of air quality components with myocardial risk.

Review of fluoride toxicity studies

Sharma D, Singh A, Verma K, Paliwal S, Sharma S, Dwivedi J. Fluoride: A review of pre-clinical and clinical studies. Environmental toxicology and pharmacology. 2017 Dec;56:297-313. doi: 10.1016/j.etap.2017.10.008.

Fluoride is ubiquitous in environment and profound in bones, teeth and calcified tissues of human body. Fluoride has been the topic of regular discussion and investigations. Besides its toxicity, fluoride has also been examined for its beneficial effects like prevention and treatment of tooth decay, microbial infection, inflammation, cancer, occurrence of renal stone and many more. Since last many decades, several efforts have been made at pre-clinical and clinical level to understand role of fluoride in biological system. The present review gives a brief account of prevalence, sources of fluoride toxicity and pre-clinical and clinical studies carried out on effects of fluoride in last six decades.

Skeletal fluorosis, Sri Lanka

Hewavithana PB, Jayawardhane WM, Gamage R, Goonaratna C. Skeletal fluorosis in Vavuniya District: an observational study. The Ceylon medical journal. 2018 Sep 30;63(3):139-142.

BACKGROUND: The WHO recommended safe upper limit for fluoride in drinking water is 1.5 mg/l. Groundwater sources in many parts of Sri Lanka often exceed this limit. The high fluoride content of groundwater and high environmental temperatures in Vavuniya District predispose to pre-skeletal fluorosis and skeletal fluorosis in adults.

OBJECTIVES: To identify residents of Vavuniya District with clinical features of pre-skeletal and skeletal fluorosis; to describe their clinical, biochemical and radiographic features; to determine the fluoride content of blood and urine in individuals with established diagnoses, and of their drinking water.

METHODS: In 98 volunteers we detected 60 with clinical features of pre-skeletal and skeletal fluorosis. Clinical examination, biochemical and radiographic investigations were performed. Forty four with confounding factors were excluded. The balance 16 had radiographic investigation for fluoride bone disease, and assessment of clinical features for pre-skeletal fluorosis. The radiographic criteria of skeletal fluorosis were trabecular haziness, osteosclerosis, osteophytes, cortical thickening and ligamentous or muscle attachment ossification. All 16 had “spot” samples of 15 ml of venous blood taken for biochemical tests and fluoride estimation; and 30 ml of urine, and water from 16 dug wells for fluoride.

RESULTS: The 16 selected (11 males) had BMI between 20.6 and 31.9 kg/m2, and were between 22 and 84 years (x̅ = 59.9 + 20.4). They used water from domestic dug wells for drinking. All had adequate renal function. All serum and urine samples had raised fluoride levels way above the reference ranges for serum (0.02 – 0.18 mg/l) and urine (0.6 – 2.0 mg/l). The 16 water samples showed a mean fluoride content of 2.90 +0.93 mg/l.

INTERPRETATION: In a cohort of 60 individuals in Vavuniya with symptoms suggestive of skeletal fluoride toxicity, 6 had skeletal fluorosis, 10 had pre-skeletal fluorosis, and groundwater sources had fluoride levels much higher than WHO recommended upper limit for drinking water. Residents in Vavuniya are predisposed to pre-skeletal and skeletal fluorosis. All 16 had been misdiagnosed as various types of arthritis.

Recent study attempts to “prop-up” community fluoridation advocacy

Spencer AJ, Do LG, Ha DH. Contemporary evidence on the effectiveness of water fluoridation in the prevention of childhood caries. Community Dent Oral Epidemiol. 2018 Aug;46(4):407-415. doi: 10.1111/cdoe.12384. 

BACKGROUND: Water fluoridation’s effectiveness has been reaffirmed by systematic reviews. However, most of the included nonrandomised controlled before and after studies were conducted pre-1975. Opportunity for such studies is limited in a steady state of community fluoridation programmes. As an alternative for evidence to support or refute the effectiveness of water fluoridation, this study used data from a recent national child oral health study to examine associations between lifetime exposure to fluoridated water (%LEFW) and childhood caries.

METHODS: A population-based study of child oral health in Australia was conducted in 2012-2014, using complex sampling and weighting procedures. Parents provided detailed household information and children underwent oral epidemiological examination by trained examiners. Residential history from birth was used to calculate %LEFW. Caries prevalence (dmfs/DMFS>0) and experience (dmfs/DMFS) in both primary (age 5-8) and permanent dentitions (age 9-14) were estimated. Socioeconomic factors that were significantly different by %LEFW were then used as covariates in multivariable log-Poisson regression models for each caries outcome by %LEFW.

RESULTS: A total of 24 664 children had complete data. Caries prevalence and experience were higher among 5-8-year-old children with lower %LEFW (46.9%; 4.27 surfaces) than those with 100%LEFW (31.5%; 1.98 surfaces) and for the 9-14-year-old children with lower %LEFW (37.0%; 1.34 surfaces) than those with 100%LEFW (25.0%; 0.67 surfaces). In the multivariable models, the prevalence ratios for primary and permanent caries were significant for the two lower exposure groups against the 100%LEFW group. Similarly, the mean ratios for primary dmfs were significant for all three lower exposure groups and for permanent DMFS were significant for the two lower exposure groups against the 100%LEFW group. Mean ratios for the 0%LEFW compared to the 100%LEFW group were 2.10 (1.83-2.40) for dmfs and 1.82 (1.57-2.10) for DMFS.

CONCLUSION: Analysis of contemporary data representative of the Australian child population found consistent associations between %LEFW and childhood caries, which persisted when socioeconomic differences were adjusted across exposure groups, supporting the continued effectiveness of water fluoridation.

Heat-mortality impacts declined over the past decades

Ana M. Vicedo-Cabrera et al. A multi-country analysis on potential adaptive mechanisms to cold and heat in a changing climate Environment International Volume 111, February 2018, Pages 239-246


Temporal variation of temperature-health associations depends on the combination of two pathways: pure adaptation to increasingly warmer temperatures due to climate change, and other attenuation mechanisms due to non-climate factors such as infrastructural changes and improved health care. Disentangling these pathways is critical for assessing climate change impacts and for planning public health and climate policies. We present evidence on this topic by assessing temporal trends in cold- and heat-attributable mortality risks in a multi-country investigation.


Trends in country-specific attributable mortality fractions (AFs) for cold and heat (defined as below/above minimum mortality temperature, respectively) in 305 locations within 10 countries (1985–2012) were estimated using a two-stage time-series design with time-varying distributed lag non-linear models. To separate the contribution of pure adaptation to increasing temperatures and active changes in susceptibility (non-climate driven mechanisms) to heat and cold, we compared observed yearly-AFs with those predicted in two counterfactual scenarios: trends driven by either (1) changes in exposure-response function (assuming a constant temperature distribution), (2) or changes in temperature distribution (assuming constant exposure-response relationships). This comparison provides insights about the potential mechanisms and pace of adaptation in each population.


Heat-related AFs decreased in all countries (ranging from 0.45–1.66% to 0.15–0.93%, in the first and last 5-year periods, respectively) except in Australia, Ireland and UK. Different patterns were found for cold (where AFs ranged from 5.57–15.43% to 2.16–8.91%), showing either decreasing (Brazil, Japan, Spain, Australia and Ireland), increasing (USA), or stable trends (Canada, South Korea and UK). Heat-AF trends were mostly driven by changes in exposure-response associations due to modified susceptibility to temperature, whereas no clear patterns were observed for cold.


Our findings suggest a decrease in heat-mortality impacts over the past decades, well beyond those expected from a pure adaptation to changes in temperature due to the observed warming. This indicates that there is scope for the development of public health strategies to mitigate heat-related climate change impacts. In contrast, no clear conclusions were found for cold. Further investigations should focus on identification of factors defining these changes in susceptibility.

Presumption of “safety” drives fluoridation study interpretation

Slade GD, Grider WB, Maas WR, Sanders AE. Water Fluoridation and Dental Caries in U.S. Children and Adolescents. J Dent Res. 2018 Sep;97(10):1122-1128. doi: 10.1177/0022034518774331.

Fluoridation of America’s drinking water was among the great public health achievements of the 20th century. Yet there is a paucity of studies from the past 3 decades investigating its dental health benefits in the U.S. This cross-sectional study sought to evaluate associations between availability of community water fluoridation (CWF) and dental caries experience in the U.S. child and adolescent population. County-level estimates of the percentage of population served by CWF (% CWF) from the Centers for Disease Control and Prevention’s Water Fluoridation Reporting System were merged with dental examination data from 10 y of National Health and Nutrition Examination Surveys (1999 to 2004 and 2011 to 2014). Dental caries experience in the primary dentition (decayed and filled tooth surfaces [dfs]) was calculated for 7,000 children aged 2 to 8 y and in the permanent dentition (decayed, missing, and filled tooth surfaces [DMFS]) for 12,604 children and adolescents aged 6 to 17 y. Linear regression models estimated associations between % CWF and dental caries experience with adjustment for sociodemographic characteristics: age, sex, race/ethnicity, rural-urban location, head-of-household education, and period since last dental visit. Sensitivity analysis excluded counties fluoridated after 1998. In unadjusted analysis, caries experience in the primary dentition was lower in counties with ≥75% CWF (mean dfs = 3.3; 95% confidence limit [CL] = 2.8, 3.7) than in counties with <75% CWF (mean dfs = 4.6; 95% CL = 3.9, 5.4), a prevented fraction of 30% (95% CL = 11, 48). The difference was also statistically significant, although less pronounced, in the permanent dentition: mean DMFS (95% CL) was 2.2 (2.0, 2.4) and 1.9 (1.8, 2.1), respectively, representing a prevented fraction of 12% (95% CL = 1, 23). Statistically significant associations likewise were seen when % CWF was modeled as a continuum, and differences tended to increase in covariate-adjusted analysis and in sensitivity analysis. These findings confirm a substantial caries-preventive benefit of CWF for U.S. children and that the benefit is most pronounced in primary teeth.