Human Biological Monitoring of Diisononyl Phthalate and Diisodecyl Phthalate: A Review

High molecular-weight phthalates, such as diisononyl phthalate (DINP), and diisodecyl phthalate (DIDP), are widely used as plasticizers in the manufacturing of polymers and consumer products. Human biological monitoring studies have employed the metabolites of DINP and DIDP as biomarkers to assess human exposure. In this review, we summarize and analyze publicly available scientific data on chemistry, metabolism, and excretion kinetics, of DINP and DIDP, to identify specific and sensitive metabolites. Human biological monitoring data on DINP and DIDP are scrutinised to assess the suitability of these metabolites as biomarkers of exposure. Results from studies carried out in animals and humans indicate that phthalates are metabolised rapidly and do not bioaccmulate. During Phase-I metabolism, ester hydrolysis of DINP and DIDP leads to the formation of hydrolytic monoesters. These primary metabolites undergo further oxidation reactions to produce secondary metabolites. Hence, the levels of secondary metabolites of DINP and DIDP in urine are found to be always higher than the primary metabolites. Results from human biological monitoring studies have shown that the secondary metabolites of DINP and DIDP in urine were detected in almost all tested samples, while the primary metabolites were detected in only about 10% of the samples. This indicates that the secondary metabolites are very sensitive biomarkers of DINP/DIDP exposure while primary metabolites are not. The NHANES data indicate that the median concentrations of MCIOP and MCINP (secondary metabolites of DINP and DIDP, resp.) at a population level are about 5.1 μg/L and 2.7 μg/L, respectively. Moreover, the available biological monitoring data suggest that infants/children are exposed to higher levels of phthalates than adults

Analysis of steroid hormones as endocrine disruptors in sewage, seawater and mussels using GC-MS techniques

In recent years, there has been an increased concern over the appearance of endocrine dismpting chemicals (EDCs) in the aquatic environment due to their potential reproductive and early developmental toxicity to wildlife population. Municipal and industrial sewage effluents are considered as the major sources of EDCs. Among different classes of EDCs, natural and synthetic steroid estrogens have been identified as the most potent EDCs, as they can induce feminization in fish even at trace levels. Steroid hormones undergo extensive biodegradation during secondary treatment in municipal wastewater treatment processes. However, in Atlantic Canada only 50% of the population has municipal sewage treatment facilities. In many coastal towns and cities, including Halifax, Nova Scotia, and St. John's, Newfoundland & Labrador the raw sewage is directly discharged into harbours. Needless to say, sewage-related contaminants pose a serious threat to the marine ecosystem in these areas. -- Mussels are widely used to assess environmental impact of pollutants (metals and organics) in the marine environment. Mussels living near sewage outfalls may be exposed to constant levels of steroid estrogens through their food and respiration. This study examines whether these organisms can be used as a good bio-indicator for steroidal pollution. In this work, the analysis of steroid estrogens (estrone, estradiol, ethynylestradiol, diethylstilbestrol and mestranol) and fecal biomarker coprostanol in raw sewage, seawater and mussels collected from St. John's and Halifax harbours was undertaken. Two analytical methods based on GC- (ion trap) MS/MS were developed for mussel tissue and sewage analysis. A major factor in the success of method development was the removal of interferences of tissue matrix. Performance characteristics of these methods were evaluated using careful recovery experiments. Percentage recovery of analytes measured by spiking anaiyte standards in mussel and distilled water were >60% and >80% respectively. Reproducibility of the analytical methods calculated based on relative standard deviation values ranged from 7.7% to 13.3% for the analysis of mussel tissue and 3.0% to 6.8% for sewage effluents. This study reveals the presence of steroid estrogens estrone (E₁) and estradiol (E₂) and of high levels of coprostanol in seawater samples collected from both harbours indicating extensive fecal contamination and significant steroidal pollution. In addition, estrone (E₁) was measured in mussel samples obtained from some of the harbour locations. Concentration of coprostanol in mussels was used as a qualitative indicator of relative sewage contamination among the sampling sites. Further research should be undertaken to sample a larger number of mussel sites over a longer period to determine whether these organisms are reliable bio-indicators of steroidal pollution

Urinary excretion and daily intake rates of diethyl phthalate in the general Canadian population

AbstractWe have analyzed the trends in the body-weight-adjusted urinary monoethyl phthalate (MEP) concentrations and the diethyl ethyl phthalate (DEP) daily intake estimates in the general Canadian population (aged 6-49 years) using the Canadian Health Measures Survey 2007–2009 dataset. The creatinine correction approach, as well as the urine volume approach in a simple one compartment model were used to calculate the daily urinary MEP excretion rates and DEP intake rates in individual survey participants. Using multiple regression models, we have estimated least square geometric means (LSGMs) of body-weight-adjusted MEP concentration, daily excretion and intake rates among different age groups and sex. We observed that body weight affects the trends in the MEP concentrations significantly among children (aged 6–11years), adolescents (aged 12–19years) and adults (aged 20–49years). The body-weight-adjusted MEP concentrations in children were significantly higher than those in adults. On the other hand the DEP daily intakes in children were significantly lower than those in adults. We did not observe any differences in the DEP daily intake rates between males and females. Although the urinary MEP concentrations are correlated well with DEP daily intake estimates in the overall population, one should be cautious when directly using the urinary concentrations to compare the intake trends in the sub-populations (e.g. children vs. adults) as these trends are governed by additional physiological factors. The DEP daily intake calculated using the creatinine approach and that using the urine volume approach were similar to each other. The estimated geometric mean and 95th percentile of DEP daily intake in the general Canadian population are 2 and 20μg/kg-bw/day, respectively. These daily intake estimates are significantly lower than the US Environmental Protection Agency's oral reference dose of 800μg/kg-bw/day

The Association Between Urinary Phthalates and Lung Function

OBJECTIVE: To investigate the influence of phthalate exposure on lung function in the Canadian population. METHODS: We tested the association between 1-second forced expiratory volume (FEV(l)), forced vital capacity (FVC), and urinary phthalate metabolite levels in a nationally representative sample of 3147, from 6 to 49 years old. RESULTS: An interquartile increase in mono-n-butyl phthalate was associated with decreases in percent predicted FEV(1) of 0.8% (95% confidence interval = 0.3 to 1.4) and in FVC of 0.9% (95% confidence interval = 0.3 to 1.5). Results were similar for mono-3-carboxypropyl phthalate, mono-benzyl phthalate, and di(2-ethylhexyl) phthalate metabolites, but significant effects of the latter were only seen in males and those at least 17 years old. CONCLUSIONS: These results provide evidence that phthalate exposure may adversely affect lung function in the Canadian population. Given that these chemicals are ubiquitous, the population health burden may be significant if the associations were causal

An overview of human biomonitoring of environmental chemicals in the Canadian Health Measures Survey: 2007–2019

AbstractHuman biomonitoring (HBM) is used to indicate and quantify exposure by measuring environmental chemicals, their metabolites or reaction products in biological specimens. The biomonitoring component of the Canadian Health Measures Survey (CHMS) is the most comprehensive initiative providing general population HBM data in Canada.The CHMS is an ongoing cross-sectional direct measures survey implemented in 2-year cycles. It provides nationally-representative data on health, nutritional status, environmental exposures, and related risks and protective characteristics. The survey follows a robust planning, design and sampling protocol as well as a comprehensive quality assurance and quality control regime implemented for all aspect of the survey to ensure the validity of the HBM results.HBM blood and urine data are available for CHMS cycles 1 (2007–2009), 2 (2009–2011) and 3 (2012–2013). Field collection has been completed for cycle 4 (2014–2015), with cycle 5 (2016–2017) in progress and cycle 6 planning (2018–2019) being finalized. Biomonitoring results for 279 chemicals are expected over the six cycles of the CHMS (220 in individual blood, urine or hair samples, and 59 in pooled serum samples). The chemicals include metals and trace elements, polychlorinated biphenyls (PCBs), organochlorines, flame retardants, perfluoroalkyl substances, volatile organic compounds (VOCs) and metabolites, environmental phenols, triclocarban, acrylamide, pesticides (e.g., triazines, carbamates, organophosphates, phenoxy, pyrethroids) and/or their metabolites, chlorophenols, polycyclic aromatic hydrocarbon (PAH) metabolites, phthalates and alternate plasticizer metabolites, and tobacco biomarkers. Approximately one half of the chemicals measured in individual blood and urine samples over the first three cycles were detected in more than 60% of samples.CHMS biomonitoring data have been used to establish baseline HBM concentrations in Canadians; inform public health, regulatory risk assessment and management decisions; and fulfil national and international reporting requirements. Concurrent efforts are underway in Canada to develop statistically- and risk-based concepts and tools to interpret biomonitoring data