Chemical Contamination of Green Turtle (Chelonia mydas) Eggs in Peninsular Malaysia: Implications for Conservation and Public Health

Background

Persistent organic pollutants (POPs)—such as organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs)—and heavy metals have been reported in sea turtles at various stages of their life cycle. These chemicals can disrupt development and function of wildlife. Furthermore, in areas such as Peninsular Malaysia, where the human consumption of sea turtle eggs is prevalent, egg contamination may also have public health implications.

Objective

In the present study we investigated conservation and human health risks associated with the chemical contamination of green turtle (Chelonia mydas) eggs in Peninsular Malaysia.

Methods

Fifty-five C. mydas eggs were collected from markets in Peninsular Malaysia and analyzed for POPs and heavy metals. We conducted screening risk assessments (SRAs) and calculated the percent of acceptable daily intake (ADI) for POPs and metals to assess conservation and human health risks associated with egg contamination.

Results

C. mydas eggs were available in 9 of the 33 markets visited. These eggs came from seven nesting areas from as far away as Borneo Malaysia. SRAs indicated a significant risk to embryonic development associated with the observed arsenic concentrations. Furthermore, the concentrations of coplanar PCBs represented 3 300 times the ADI values set by the World Health Organization.

Conclusions

The concentrations of POPs and heavy metals reported in C. mydas eggs from markets in Peninsular Malaysia pose considerable risks to sea turtle conservation and human health.     

A cross-sectional study of the association between persistent organochlorine pollutants and diabetes

Background  

Experimental evidence supports the hypothesis that persistent organochlorine pollutants (POPs) may cause type 2 diabetes mellitus, whereas there is no fully convincing epidemiological evidence for such an association. In Sweden the most important source of POP exposure is fatty fish. We have assessed the association between serum levels of POPs and prevalence of diabetes in Swedish fishermen and their wives, with high consumption of fatty fish from the Baltic Sea.     

The impacts of emission trends of POPs on human concentration dynamics: Lessons learned from a longitudinal study in Norway (1979–2007)

Background

In this short communication, our focus is on the relationship between human concentrations of select persistent organic pollutants (POPs) and environmental emissions. It is based on a longitudinal study (1979–2007) conducted in Norway.

A Multi-Individual Pharmacokinetic Model Framework for Interpreting Time Trends of Persistent Chemicals in Human Populations: Application to a Postban Situation

Background

Human milk and blood are monitored to detect time trends of persistent organic pollutants (POPs) in humans. It is current practice to use log-linear regression to fit time series of averaged cross-sectional biomonitoring data, here referred to as cross-sectional trend data (CSTD).

Objective

The goals of our study are to clarify the interpretation of half-lives derived from fitting exponential functions to declining CSTD and to provide a method of estimating human elimination half-lives from CSTD collected in a postban situation.

Methods

We developed a multi-individual pharmacokinetic model framework and present analytical solutions for a postban period. For this case, the framework quantitatively describes the relationships among the half-life for reduction of body burdens of POPs derived from CSTD, the half-life describing decline in daily intake, and the half-life of elimination from the human body.

Results

The half-life derived from exponential fitting of CSTD collected under postban conditions describes the exposure trend and is independent of human elimination kinetics. We use a case study of DDT (dichlorodiphenyltrichloroethane) to show that CSTD can be combined with exposure data obtained from total diet studies to estimate elimination kinetics of POPs for humans under background exposure conditions.

Conclusions

CSTD provide quantitative information about trends in human exposure and can be combined with exposure studies to estimate elimination kinetics. The full utility of these data has not been exploited so far. An efficient and informative monitoring strategy for banned POPs in humans would coordinate sampling of consistent sets of CSTD from young adults with total diet studies.     

The effect of exposure route on the distribution and excretion of hexachloronaphthalene in rats

Objectives  

Polychlorinated naphthalenes (PCNs), like other persistent organic pollutants (POPs), are widespread, global environmental contaminants. These compounds still represent a great environmental problem, mostly because of the risk of secondary air pollution. They are characterized by long durability and tendency to bioaccumulate, which means that they are practically ubiquitous in all environmental media and ecosystems. The aim of this study was to investigate the distribution and excretion of hexachloronaphthalene (HxCN) in rats following a single intraperitoneal or intragastrical administration.     

Recommendations for Evaluating Temporal Trends of Persistent Organic Pollutants in Breast Milk

Background:

Biomonitoring data of persistent organic pollutants (POPs) in breast milk are increasingly collected and available for quantitative analysis of levels and time trends. A common approach is to apply log-linear regression to calculate doubling and halving times of the POP concentrations based on the temporal trend observed in breast milk. However, there are different, sometimes conflicting interpretations of these doubling and halving times.

Objectives:

We provide a mechanistic understanding of doubling and halving times where possible. Five recommendations are proposed for dealing with POP concentration trends in breast milk during three distinct periods (pre-ban, transition, post-ban period).

Discussion:

Using temporal trends of BDE-47 and PCB-153 in breast milk data, we show which information can be gained from the time-trend data. To this end, we analyzed time trends of hypothetical POPs for different periods with time-variant exposure and different intrinsic elimination half-lives, using a dynamic population-based pharmacokinetic model. Different pieces of information can be extracted from time-trend data from different periods. The analysis of trends of short-lived POPs is rather straightforward and facilitates extraction of the intrinsic elimination half-lives from the breast milk data. However, trends of slowly eliminated POPs only provide indications for the exposure time trend.

Conclusions:

Time-trend data of rapidly eliminated POPs provide information on exposure time trends and elimination half-lives. Temporal trends of slowly eliminated POPs are more complicated to interpret, and the extraction of exposure time trends and elimination half-lives require data sets covering several decades.

Citation:

Gyalpo T, Scheringer M, Hungerbühler K. 2016. Recommendations for evaluating temporal trends of persistent organic pollutants in breast milk. Environ Health Perspect 124:881–885; http://dx.doi.org/10.1289/ehp.1510219     

Species-Specific Differential AhR Expression Protects Human Neural Progenitor Cells against Developmental Neurotoxicity of PAHs

Background

Because of their lipophilicity, persistent organic pollutants (POPs) cross the human placenta, possibly affecting central nervous system development. Most POPs are known aryl hydrocarbon receptor (AhR) ligands and activators of AhR signaling. Therefore, AhR activation has been suggested to cause developmental neurotoxicity (DNT).

Objective

We studied the effects of AhR ligands on basic processes of brain development in two comparative in vitro systems to determine whether AhR-activation is the underlying mechanism for reported DNT of POPs in humans.

Methods

We employed neurosphere cultures based on human neural progenitor cells (hNPCs) and wild-type and AhR-deficient mouse NPCs (mNPCs) and studied the effects of different AhR agonists [3-methylcholanthrene (3-MC), benzo(a)pyrene [B(a)P], and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)] and an antagonist [3′-methoxy-4′-nitroflavone (MNF)] on neurosphere development. Moreover, we analyzed expression of AhR and genes involved in AhR signaling.

Results

In contrast to wild-type mNPCs, hNPCs and AhR-deficient mNPCs were insensitive to AhR agonism or antagonism. Although AhR modulation attenuated wild-type mNPC proliferation and migration, hNPCs and AhR-deficient mNPCs remained unaffected. Results also suggest that species-specific differences resulted from nonfunctional AhR signaling in hNPCs.

Conclusion

Our findings suggest that in contrast to wild-type mNPCs, hNPCs were protected against polycyclic aromatic hydrocarbon–induced DNT because of an absence of AhR. This difference may contribute to species-specific differences in sensitivity to POPs.     

Persistent Organic Pollutant Residues in Human Fetal Liver and Placenta from Greater Montreal,Quebec: A Longitudinal Study from 1998 through 2006

Background

There is general concern that persistent organic pollutants (POPs) found in the environment, wildlife, food, water, house dust, human tissues, and fluids may alter normal human physiologic activities (e.g., fetal development, immune and endocrine systems). Although the levels of some POPs [polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCs)] in these matrices have decreased after their ban, others [polybrominated diphenyl ethers (PBDEs)] have increased in recent years.

Objective

To determine the longitudinal trend of specific POPs in human fetal tissues for risk assessment purposes.

Methods

We analyzed early to mid-gestation fetal liver (n = 52) and placental (n = 60) tissues, obtained after elective abortions during 1998–2006, for selected PBDEs, PCBs, and OCs using gas chromatography–mass spectroscopy.

Results

Total PBDEs in fetal liver increased over time (mean ± SE: 1998, 284.4 ± 229.8 ng/g lipid; 2006, 1,607.7 ± 605.9; p < 0.03), whereas placental levels were generally lower, with no clear trend. Low levels of PCBs and OCs varied yearly, with no evident trend. The major analytes in 1998 were OCs (liver, 49%; placenta, 71%), whereas the major analytes in 2006 were PBDEs (liver, 89%; placenta, 98%). The 1998–2006 tissue PBDE congener profile is similar to that of DE-71, a commercial primarily pentabrominated diphenyl ether mixture manufactured in North America.

Conclusions

Although commercial production of penta- and octa-brominated diphenyl ethers in North America was halted in 2004, their concentrations in fetal liver and placenta are now greater than the tissue burdens for the analyzed OCs and PCBs. Our findings also demonstrate that PBDEs accumulate within the fetal compartment at a very early stage in gestation.     

The Pine River Statement: Human Health Consequences of DDT Use

Objectives

Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure.

Data sources and extraction

We conducted a PubMed search in October 2008 and retrieved 494 studies.

Data synthesis

Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children.

Conclusions

Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDT.     

Hazardous waste sites and stroke in New York State

Background -  

Environmental exposure to persistent organic pollutants (POPs) may lead to elevation of serum lipids, increasing risk of atherosclerosis with thromboembolism, a recognized cause of stroke. We tested the hypothesis that exposure to contaminants from residence near hazardous waste sites in New York State influences the occurrence of stroke.     

Global DNA Hypomethylation Is Associated with High Serum-Persistent Organic Pollutants in Greenlandic Inuit

Background

Persistent organic pollutants (POPs) may influence epigenetic mechanisms; therefore, they could affect chromosomal stability and gene expression. DNA methylation, an epigenetic mechanism, has been associated with cancer initiation and progression. Greenlandic Inuit have some of the highest reported POP levels worldwide.

Objective

Our aim in this study was to evaluate the relationship between plasma POPs concentrations and global DNA methylation (percent 5-methylcytosine) in DNA extracted from blood samples from 70 Greenlandic Inuit. Blood samples were collected under the Arctic Monitoring and Assessment Program and previously analyzed for a battery of POPs.

Methods

We used pyrosequencing to estimate global DNA methylation via Alu and LINE-1 assays of bisulfite-treated DNA. We investigated correlations between plasma POP concentrations and global DNA methylation via correlation coefficients and linear regression analyses.

Results

We found inverse correlations between percents methylcytosine and many of the POP concentrations measured. Linear regressions, adjusting for age and cigarette smoking, showed statistically significant inverse linear relationships mainly for the Alu assay for p,p′-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane; β = −0.26), p,p′-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene; β = −0.38], β-hexachlorocyclohexane (β = −0.48), oxychlordane (β = −0.32), α-chlordane (β = −0.75), mirex (β = −0.27), sum of polychlorinated biphenyls (β = −0.56), and sum of all POPs (β = −0.48). Linear regressions for the LINE-1 assay showed β estimates of similar magnitudes to those using the Alu assay, however, none was statistically significant.

Conclusions

This is the first study to investigate environmental exposure to POPs and DNA methylation levels in a human population. Global methylation levels were inversely associated with blood plasma levels for several POPs and merit further investigation.     

Low Dose of Some Persistent Organic Pollutants Predicts Type 2 Diabetes: A Nested Case–Control Study

Background

Low doses of some persistent organic pollutants (POPs) associate cross-sectionally with type 2 diabetes, whereas associations with high POP exposures are inconsistent.

Objectives

We investigated whether several POPs prospectively predict type 2 diabetes within the Coronary Artery Risk Development in Young Adults (CARDIA) cohort.

Methods

Participants in this nested case–control study were diabetes free in 1987–1988. By 2005–2006, the 90 controls remained free of diabetes, whereas the 90 cases developed diabetes. Using serum collected in 1987–1988, we measured 8 organochlorine pesticides, 22 polychlorinated biphenyl congeners (PCBs), and 1 polybrominated biphenyl (PBB). We compared POP concentrations from CARDIA and the National Health and Nutrition Examination Survey (NHANES) in 2003–2004. We computed odds ratios (ORs) for incident diabetes using logistic regression analysis.

Results

Chlorinated POPs in CARDIA in 1987–1988 were much higher than corresponding NHANES 2003-2004 concentrations. POPs showed nonlinear associations with diabetes risk. The highest risk was observed in the second quartiles of trans-nonachlor, oxychlordane, mirex, highly chlorinated PCBs, and PBB153—a finding that suggests low-dose effects. We concentrated risk by summing these POPs and isolated very low concentrations of multiple POPs in the lowest sextile of the sum. The adjusted OR in the second sextile vs. the lowest sextile was 5.3 overall and 20.1 for body mass index ≥ 30 kg/m².

Conclusions

Several POPs at low doses similar to current exposure levels may increase diabetes risk, possibly through endocrine disruption. Certain POPs may a play a role in the current epidemic of diabetes, which has been attributed to obesity.     

Interaction Between Persistent Organic Pollutants and C-reactive Protein in Estimating Insulin Resistance Among Non-diabetic Adults

Objectives

Chronic inflammation is now thought to play a key pathogenetic role in the associations of obesity with insulin resistance and diabetes. Based on our recent findings on persistent organic pollutants (POPs) including the lack of an association between obesity and either insulin resistance or diabetes prevalence among subjects with very low concentrations of POPs, we hypothesized that POP concentrations may be associated with inflammation and modify the associations between inflammation and insulin resistance in non-diabetic subjects.

Methods

Cross-sectional associations among serum POPs, C-reactive protein (CRP), and homeostasis model assessment of insulin resistance (HOMA-IR) were investigated in 748 non-diabetic participants aged ≥20 years. Nineteen types of POPs in 5 subclasses were selected because the POPs were detectable in ≥60% of the participants.

Results

Among the five subclasses of POPs, only organochlorine (OC) pesticides showed positive associations with CRP concentrations, while polychlorinated biphenyls (PCBs) showed inverse associations with CRP concentrations. There were statistically significant interactions between CRP and OC pesticides and between CRP and PCBs, in estimating HOMA-IR (P for interaction <0.01 and <0.01, respectively). CRP was not associated with HOMA-IR among subjects with low concentrations of OC pesticides or PCBs, while CRP was strongly associated with HOMA-IR among subjects with high concentrations of these POPs.

Conclusions

In the current study, OC pesticides were associated with increased levels of CRP, a marker of inflammation, and both OC pesticides and PCBs may also modify the associations between CRP and insulin resistance.     

A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases

Background:

A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published.

Objectives:

We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases.

Methods:

For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes.

Conclusions:

Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies.

Citation:

Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that link different POPs to common metabolic diseases. Environ Health Perspect 124:1034–1041; http://dx.doi.org/10.1289/ehp.1510308     

Association between serum concentrations of persistent organic pollutants and smoking in Koreans: A cross-sectional study

Background

Studies on the associations between persistent organic pollutants (POPs) and smoking according to gender and smoking amount (cigarettes/day) are limited, and the results regarding the relationship between POPs and smoking are not completely consistent across studies.

Organochlorine Exposure and Incidence of Diabetes in a Cohort of Great Lakes Sport Fish Consumers

Background

Studies have demonstrated ubiquitous human exposure to persistent organic pollutants (POPs) such as p,p′-diphenyldichloroethene (DDE) and polychlorinated biphenyls (PCBs). Although there is considerable evidence that POP exposures are associated with prevalent diabetes, these studies do not establish causality because the cross-sectional study design does not allow for assessment of temporality of the exposure–disease association. Prospective studies, however, have been lacking.

Objectives

This study was designed to determine whether POP body burdens are related to incidence of diabetes in a cohort of Great Lakes sport fish consumers.

Methods

The cohort was established in the early 1990s and followed through 2005. We tested serum for DDE and PCB congeners and assessed diabetes diagnosis, demographics, and fish consumption. Associations of diabetes with exposures were examined prospectively in participants without diabetes in 1994–1995, followed through 2005. Annual percent changes in DDE and PCB-132/153 from 1994 to 2005 were examined by diabetes status.

Results

DDE exposure was associated with incident diabetes. Incident diabetes was not associated with mono-ortho PCB-118, total PCBs, or years of sport fish consumption. Annual percent change in DDE and PCB-132/153 did not differ significantly by diabetes status.

Conclusions

This study demonstrates an association between DDE exposure and incident diabetes. The findings of an association of DDE with incident diabetes and the lack of effect of diabetes on annual percent change in POPs do not support the hypothesis that associations of POPs with diabetes are attributable to reverse causality. Additional studies should address the biological pathways by which DDE could affect glucose homeostasis.     

Associations of Serum Concentrations of Persistent Organic Pollutants with the Prevalence of Periodontal Disease and Subpopulations of White Blood Cells

Background

Persistent organic pollutants (POPs), which are endocrine disruptors that accumulate in adipose tissue, can increase the risk of periodontal disease through the disturbance of the immune system.

Objective

We examined associations of background exposure to POPs with periodontal disease in the general population.

Design

Cross-sectional associations of concentrations of serum POPs with the prevalence of periodontal disease were investigated in 1,234 adults ≥ 20 years of age in the National Health and Nutrition Examination Survey 1999–2002.

Results

Among several POPs, organochlorine (OC) pesticides were most strongly associated with periodontal disease. Adjusted odds ratios across quintiles of OC pesticides were 1.0, 1.3, 1.7, 2.4, and 2.7 (p for trend < 0.01) for the presence in any site of clinical attachment loss ≥ 4 mm and 1.0, 1.7, 2.6, 3.4, and 3.7 (p for trend < 0.01) for the presence of pocket depth ≥ 4 mm. Polychlorinated biphenyls and polychlorinated dibenzo-p-dioxins also showed significant positive associations with one or both definitions of periodontal disease. Results did not materially change when continuous variables of clinical attachment loss or pocket depth were used as outcomes. Although participants with periodontal disease had higher white blood cell and neutrophil counts, neutrophil counts were inversely related to OC pesticides (p for trend < 0.01). These inverse associations did not change after excluding subjects with C-reactive protein ≥ 3 mg/L.

Conclusion

POPs, especially OC pesticides, were positively associated with periodontal disease, possibly through immunomodulation due to OC pesticides.     

Perfluorinated compounds are related to breast cancer risk in greenlandic inuit: A case control study

Background

Breast cancer (BC) is the most common cancer for women in the western world. From very few cases an extraordinary increase in BC was observed in the Inuit population of Greenland and Canada although still lower than in western populations. Previous data suggest that exposure to persistent organic pollutants (POPs) might contribute to the risk of BC. Rat studies showed that perfluorinated compounds (PFCs) cause significantly increase in mammary fibroadenomas. This study aimed at evaluating the association between serum levels of POPs/PFCs in Greenlandic Inuit BC cases and their controls, and whether the combined POP related effect on nuclear hormone receptors affect BC risk.

Methods

Thirty-one BC cases and 115 controls were sampled during 2000-2003 from various Greenlandic districts. The serum levels of POPs, PFCs, some metals and the combined serum POP related effect on estrogen- (ER), androgen- (AR) and Ah-receptor (AhR) transactivity were determined. Independent student t-test was used to compare the differences and the odds ratios were estimated by unconditional logistic regression models.

Results

We observed for the very first time a significant association between serum PFC levels and the risk of BC. The BC cases also showed a significantly higher concentration of polychlorinated biphenyls at the highest quartile. Also for the combined serum POP induced agonistic AR transactivity significant association to BC risk was found, and cases elicited a higher frequency of samples with significant POP related hormone-like agonistic ER transactivity. The AhR toxic equivalent was lowest in cases.

Conclusions

The level of serum POPs, particularly PFCs, might be risk factors in the development of BC in Inuit. Hormone disruption by the combined serum POP related xenoestrogenic and xenoandrogenic activities may contribute to the risk of developing breast cancer in Inuit. Further investigations are needed to document these study conclusions.