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The Lancet. Neurology Mar 2014Neurodevelopmental disabilities, including autism, attention-deficit hyperactivity disorder, dyslexia, and other cognitive impairments, affect millions of children... (Review)
Review
Neurodevelopmental disabilities, including autism, attention-deficit hyperactivity disorder, dyslexia, and other cognitive impairments, affect millions of children worldwide, and some diagnoses seem to be increasing in frequency. Industrial chemicals that injure the developing brain are among the known causes for this rise in prevalence. In 2006, we did a systematic review and identified five industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls, arsenic, and toluene. Since 2006, epidemiological studies have documented six additional developmental neurotoxicants-manganese, fluoride, chlorpyrifos, dichlorodiphenyltrichloroethane, tetrachloroethylene, and the polybrominated diphenyl ethers. We postulate that even more neurotoxicants remain undiscovered. To control the pandemic of developmental neurotoxicity, we propose a global prevention strategy. Untested chemicals should not be presumed to be safe to brain development, and chemicals in existing use and all new chemicals must therefore be tested for developmental neurotoxicity. To coordinate these efforts and to accelerate translation of science into prevention, we propose the urgent formation of a new international clearinghouse.
Topics: Animals; Brain; Developmental Disabilities; Environmental Exposure; Humans; Methylmercury Compounds; Neurotoxicity Syndromes; Polychlorinated Biphenyls
PubMed: 24556010
DOI: 10.1016/S1474-4422(13)70278-3 -
Environmental Health : a Global Access... May 2022To conduct a comprehensive systematic review and meta-analysis to estimate the relationship between endocrine-disrupting chemicals (EDCs), including polychlorinated... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a comprehensive systematic review and meta-analysis to estimate the relationship between endocrine-disrupting chemicals (EDCs), including polychlorinated biphenyls (PCBs), poly-brominated diphenyl ethers (PBDEs), phthalates (PAEs), and per- and polyfluoroalkyl substances (PFAS) exposure and risk of gestational diabetes mellitus (GDM).
METHODS
Relevant studies from their inception to November 2021 were identified by searching EMBASE, PubMed, and Web of Science. The cohort and case-control studies that reported effect size with 95% confidence intervals (CIs) of EDC exposure and GDM were selected. The heterogeneity among the included studies was quantified by I statistic. Publication bias was evaluated through the Begg and Egger tests.
RESULTS
Twenty-five articles with a total of 23,796 participants were found. Results indicated that exposure to PCBs has a significant influence on the incidence of GDM (OR = 1.14; 95% CI = 1.00--1.31; n = 8). The risk of GDM was found to be associated with PBDE exposure (OR = 1.32; 95% CI = 1.15-1.53; n = 4). PAEs and PFASs exposure were also positively associated with the risk of GDM, with summary ORs of 1.10 (95% CI = 1.03-1.16; n = 7 for PAEs) and 1.09 (95% CI = 1.02-1.16; n = 11 for PFASs), respectively. When only cohort studies were considered, the summary OR between PCBs exposure and the risk of GDM was 0.99 (95% CI = 0.91-1.09; n = 5). Meanwhile, the summary ORs from cohort studies for PBDEs, PAEs, and PFASs exposure were 1.12 (95% CI = 1.00-1.26; n = 2), 1.08 (95% CI = 1.02-1.15; n = 5), and 1.06 (95% CI = 1.00-1.12; n = 8), respectively. The Beggs and Egger tests did not show publication bias, and the sensitivity analyses did not change the results in this meta-analysis.
CONCLUSION
These results support that exposure to certain EDCs, including PCBs, PBDEs, PAEs, and PFAS, increase the risk of GDM. Further large-sample epidemiologic researches and mechanistic studies are needed to verify the potential relationship and biological mechanisms. These results are of public health significance because the daily EDC exposure is expected to increase the risk of GDM development.
Topics: Diabetes, Gestational; Endocrine Disruptors; Environmental Pollutants; Female; Fluorocarbons; Halogenated Diphenyl Ethers; Humans; Polychlorinated Biphenyls; Pregnancy
PubMed: 35578291
DOI: 10.1186/s12940-022-00858-8 -
Environmental Research Mar 2024Persistent organic pollutants (POPs) are chemicals characterized by their environmental persistence. Evidence suggests that exposure to POPs, which is ubiquitous, is... (Review)
Review
Per- and polyfluoroalkyl substances, polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers and dysregulation of MicroRNA expression in humans and animals-A systematic review.
BACKGROUND
Persistent organic pollutants (POPs) are chemicals characterized by their environmental persistence. Evidence suggests that exposure to POPs, which is ubiquitous, is associated with microRNA (miRNA) dysregulation. miRNA are key regulators in many physiological processes. It is thus of public health concern to understand the relationships between POPs and miRNA as related to health outcomes.
OBJECTIVES
This systematic review evaluated the relationship between widely recognized, intentionally manufactured, POPs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (dichlorodiphenyltrichloroethane [DDT], dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB]), with miRNA expression in both human and animal studies.
METHODS
We used PubMed and Embase to systematically search the literature up to September 29th, 2023. Search results for human and animal studies were included if they incorporated at least one POP of interest in relation to at least one miRNA. Data were synthesized to determine the direction and significance of associations between POPs and miRNA. We utilized ingenuity pathway analysis to review disease pathways for miRNA that were associated with POPs.
RESULTS
Our search identified 38 eligible studies: 9 in humans and 29 in model organisms. PFAS were associated with decreased expression of miR-19, miR-193b, and miR-92b, as well as increased expression of miR-128, miR-199a-3p, and miR-26b across species. PCBs were associated with increased expression of miR-15a, miR-1537, miR-21, miR-22-3p, miR-223, miR-30b, and miR-34a, as well as decreased expression of miR-130a and let-7b in both humans and animals. Pathway analysis for POP-associated miRNA identified pathways related to carcinogenesis.
DISCUSSION
This is the first systematic review of the association of POPs with miRNA in humans and model organisms. Large-scale prospective human studies are warranted to examine the role of miRNA as mediators between POPs and health outcomes.
Topics: Animals; Humans; Polychlorinated Biphenyls; Halogenated Diphenyl Ethers; Prospective Studies; Hydrocarbons, Chlorinated; Environmental Pollutants; Pesticides; MicroRNAs; Fluorocarbons
PubMed: 38056610
DOI: 10.1016/j.envres.2023.117832 -
Human Reproduction Update Feb 2021Despite increasing regulation, exposure to persistent organic pollutants (POPs) remains a serious public health concern due to their accumulation in the environment and...
BACKGROUND
Despite increasing regulation, exposure to persistent organic pollutants (POPs) remains a serious public health concern due to their accumulation in the environment and ability to biomagnify up the food chain. POPs are associated with endocrine-disrupting effects including adverse reproductive outcomes that could affect fecundability, i.e. the capacity to conceive a pregnancy, quantified as time to pregnancy (TTP).
OBJECTIVE AND RATIONALE
Results of epidemiologic studies that examine the impact of various chemical classes of POPs on TTP have not been synthesised. We undertook a systematic review to summarise the strength of evidence for associations of four common groups of POPs with couple fecundability and to identify gaps and limitations in the literature in order to inform policy decisions and future research.
SEARCH METHODS
We performed an electronic search of literature published between 1 January 2007 and 6 August 2019 in MEDLINE, EMBASE.com, Global Health, DART/TOXLINE and POPLINE. We included empirical research papers that examined human exposure to organochlorine (OC) pesticides, brominated flame retardants, polychlorinated organic compounds and/or per- and polyfluoroalkyl substances (PFAS) and considered TTP or fecundability as an outcome. Standardised forms for screening, data extraction and study quality were developed using DistillerSR software, and all reviews were completed in duplicate. We used the Newcastle-Ottawa Scale to assess risk of bias and devised additional quality metrics based on specific methodological features of fecundability studies.
OUTCOMES
The search returned 4573 articles, and 28 papers from 19 different studies met inclusion criteria. Among them, four studies measured TTP prospectively, three had data on participants' prenatal exposure, three examined associations in both male and female partners and one focused exclusively on males. Analyses varied widely in terms of exposure characterisation, precluding a meta-analytic approach. Evidence was strongest for adverse associations of female exposure to polychlorinated biphenyls with TTP, with some additional support for associations of female exposure to polybrominated diphenyl ethers and PFAS with longer TTP. Our review provided little or no support for associations between female exposure to OC pesticides or male exposure to any of the POP groups and TTP.
WIDER IMPLICATIONS
Evidence suggests that female exposure to at least some POPs may reduce fecundability. Although many of these chemicals are no longer in production, they are still detectable in human biosamples because of their persistence in the environment. Replacement chemicals that are being introduced as older ones are restricted may have similar reproductive consequences. Future studies should examine these newer POPs, assess interactions between POPs and other chemical and non-chemical exposures, investigate how POPs are distributed in and metabolised by the human body and focus on populations that may be disproportionately exposed.
Topics: Environmental Pollutants; Female; Halogenated Diphenyl Ethers; Humans; Male; Persistent Organic Pollutants; Pesticides; Polychlorinated Biphenyls; Pregnancy; Time-to-Pregnancy
PubMed: 33147335
DOI: 10.1093/humupd/dmaa037 -
Frontiers in Endocrinology 2023There are conflicting reports on the association between environmental endocrine disruptors (EEDs) and thyroid cancer. This meta-analysis aimed to elucidate the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
There are conflicting reports on the association between environmental endocrine disruptors (EEDs) and thyroid cancer. This meta-analysis aimed to elucidate the relationship between EEDs and thyroid cancer.
METHODS
We searched for epidemiological studies on EEDs and thyroid cancer published in PubMed and Web of Science up to December 2022. We then screened the articles that could extract data on EEDs concentration levels in both thyroid cancer patients and healthy controls. We excluded articles that could not calculate effect sizes, focused on other thyroid diseases, or lacked controls. Standardized mean difference (SMD) was calculated to analyze the association between EEDs and thyroid cancer. We measured the heterogeneity among the included studies using I2, assessed publication bias by Egger's and Begg's test, and evaluated article quality using the Newcastle-Ottawa Quality Score (NOS). In the end, fifteen eligible case-control studies were included.
RESULTS
Our comprehensive analysis revealed that polychlorinated biphenyls (PCBs) were negatively associated with thyroid cancer{ SMD = -0.03, 95% confidence interval (CI) = (-0.05, -0.00), P = 0.03}, while polybrominated diphenyl ethers (PBDEs), phthalates (PAEs), and heavy metals were positively associated with thyroid cancer{PBDEs: SMD = 0.14, 95%CI = (0.04, 0.23), P = 0.007; PAEs: SMD = 0.30, 95%CI = (0.02, 0.58), P = 0.04; heavy metals: SMD = 0.21, 95%CI = (0.11, 0.32), P < 0.001}. We did not find a statistically significant relationship between bisphenol A (BPA) and thyroid cancer. Most of the included studies did not show publication bias, except for those on PCBs.
DISCUSSION
Our results indicate that exposure to certain EEDs, such as PBDEs, PAEs, and heavy metals, increases the risk of thyroid cancer. However, further large-scale epidemiological studies and mechanism studies are needed to verify these potential relationships and understand the underlying biological mechanisms.
Topics: Humans; Polychlorinated Biphenyls; Endocrine Disruptors; Halogenated Diphenyl Ethers; Thyroid Neoplasms; Metals, Heavy
PubMed: 38027118
DOI: 10.3389/fendo.2023.1283087 -
Obesity Reviews : An Official Journal... Jan 2022We conducted a systematic review and meta-analysis of the associations between prenatal exposure to persistent organic pollutants (POPs) and childhood obesity. We... (Meta-Analysis)
Meta-Analysis
We conducted a systematic review and meta-analysis of the associations between prenatal exposure to persistent organic pollutants (POPs) and childhood obesity. We focused on organochlorines (dichlorodiphenyltrichloroethane [DDT], dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB], and polychlorinated biphenyls [PCBs]), perfluoroalkyl and polyfluoroalkyl substances (PFAS), and polybrominated diphenyl ethers (PBDEs) that are the POPs more widely studied in environmental birth cohorts so far. We search two databases (PubMed and Embase) through July/09/2021 and identified 33 studies reporting associations with prenatal organochlorine exposure, 21 studies reporting associations with prenatal PFAS, and five studies reporting associations with prenatal PBDEs. We conducted a qualitative review. Additionally, we performed random-effects meta-analyses of POP exposures, with data estimates from at least three prospective studies, and BMI-z. Prenatal DDE and HCB levels were associated with higher BMI z-score in childhood (beta: 0.12, 95% CI: 0.03, 0.21; I : 28.1% per study-specific log increase of DDE and beta: 0.31, 95% CI: 0.09, 0.53; I : 31.9% per study-specific log increase of HCB). No significant associations between PCB-153, PFOA, PFOS, or pentaPBDEs with childhood BMI were found in meta-analyses. In individual studies, there was inconclusive evidence that POP levels were positively associated with other obesity indicators (e.g., waist circumference).
Topics: Child; Environmental Pollutants; Female; Humans; Pediatric Obesity; Persistent Organic Pollutants; Polychlorinated Biphenyls; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies
PubMed: 34766696
DOI: 10.1111/obr.13383 -
BMJ Open Jun 2020Endocrine-disrupting chemicals (EDCs) are viewed as a major potential link between the environment and obesity development. We did a systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Endocrine-disrupting chemicals (EDCs) are viewed as a major potential link between the environment and obesity development. We did a systematic review and meta-analysis to examine the association between exposure to EDCs and obesity.
DATA SOURCES, DESIGN AND ELIGIBILITY CRITERIA
PubMed, Scopus and Web of Science were searched from inception to 6 June 2018 for studies primarily addressing the association between exposure to EDCs after the age of 2 years and anthropometric measures of obesity or body fat. The Newcastle-Ottawa scale was used to assess the risk of bias.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers screened and conducted data extraction and synthesis. A third reviewer resolved disagreements.
RESULTS
A total of 73 studies investigating bisphenol A (32 286 individuals), organochlorine compounds (34 567 individuals), phthalates (21 401 individuals), polybrominated biphenyls (2937 individuals), polycyclic aromatic hydrocarbons (5174 individuals), parabens (4097 individuals), benzoic acid (3671 individuals) and polyfluoroalkyl substances (349 individuals) met our inclusion criteria. Most had a cross-sectional design and low or medium risk of bias. In qualitative analysis, bisphenol A and phthalates were consistently associated with general and abdominal obesity, in children and adults, and some studies suggested this association was age-dependent and gender-dependent. Meta-analysis indicated a significant association between exposure to bisphenol A and overweight (OR 1.254, 95% CI 1.005 to 1.564), obesity (OR 1.503, 95% CI 1.273 to 1.774) and increased waist circumference (OR 1.503, 95% CI 1.267 to 1.783) in adults, and between exposure to 2,5-dichlorophenol and obesity in children (OR 1.8, 95% CI 1.1018 to 3.184).
CONCLUSION
Most observational studies supported a positive association between obesity and exposure to EDCs. Although causality cannot be determined from these data, they underscore the need to limit human exposure to EDCs in light of the evidence from animal and cell-based studies indicating the effects of these chemicals on adiposity.
PROSPERO REGISTRATION NUMBER
CRD42018074548.
Topics: Anthropometry; Endocrine Disruptors; Environmental Exposure; Humans; Obesity
PubMed: 32565448
DOI: 10.1136/bmjopen-2019-033509 -
Journal of Applied Toxicology : JAT Jun 2018A no-significant-risk-level of 20 mg day was derived for tetrabromobisphenol A (TBBPA). Uterine tumors (adenomas, adenocarcinomas, and malignant mixed Müllerian)...
A no-significant-risk-level of 20 mg day was derived for tetrabromobisphenol A (TBBPA). Uterine tumors (adenomas, adenocarcinomas, and malignant mixed Müllerian) observed in female Wistar Han rats from a National Toxicology Program 2-year cancer bioassay were identified as the critical effect. Studies suggest that TBBPA is acting through a non-mutagenic mode of action. Thus, the most appropriate approach to derivation of a cancer risk value based on US Environmental Protection Agency guidelines is a threshold approach, akin to a cancer safe dose (RfD ). Using the National Toxicology Program data, we utilized Benchmark dose software to derive a benchmark dose lower limit (BMDL ) as the point of departure (POD) of 103 mg kg day . The POD was adjusted to a human equivalent dose of 25.6 mg kg day using allometric scaling. We applied a composite adjustment factor of 100 to the POD to derive an RfD of 0.26 mg kg day . Based on a human body weight of 70 kg, the RfD was adjusted to a no-significant-risk-level of 20 mg day . This was compared to other available non-cancer and cancer risk values, and aligns well with our understanding of the underlying biology based on the toxicology data. Overall, the weight of evidence from animal studies indicates that TBBPA has low toxicity and suggests that high doses over long exposure durations are needed to induce uterine tumor formation. Future research needs include a thorough and detailed vetting of the proposed adverse outcome pathway, including further support for key events leading to uterine tumor formation and a quantitative weight of evidence analysis.
Topics: Animals; Body Weight; Carcinogenicity Tests; Carcinogens; Dose-Response Relationship, Drug; Female; Flame Retardants; Humans; Models, Biological; Polybrominated Biphenyls; Rats, Wistar; Risk Assessment; Species Specificity; Time Factors; Uterine Neoplasms
PubMed: 29441599
DOI: 10.1002/jat.3594