contaminants in arctic human populations...contaminants in arctic human populations khaled abass...

Contaminants in Arctic human populations

Khaled Abass

PhD, European Registered Toxicologist

Arctic Health, Faculty of Medicine, University of Oulu, Finland

One Arctic - One Health Conference - February 7-9, 2019, Oulu, FinlandEmail: [email protected]; [email protected]

mailto:[email protected]

mailto:[email protected]

Outline

• Exposure and risks

• Temporal trends of contaminants in Arctic human populations

• Chemicals of emerging Arctic concern

• Approaches to estimate human health risks

• Biomonitoring/Epidemiology

• Meta analysis and critical reviews

• Modelling and future risk prediction

• Gene regulations and expressions

Exposure and risks

Contaminants in biological matrices provides the aggregate exposure from different routes.

Persistent organic pollutants POPs :

• Criteria for determining POPs (Annex D)

• Persistence

• Bioaccumulation

• Long range transport

• Adverse effects

Stockholm Convention on POPs

The Stockholm convention on POPs initially listed 12 substances for elimination or

control under its Annexes and currently there are 23 POPs listed in the Stockholm

conventions. Although use of POPs has been either phased-out or limited, POPs still

exist in humans and biota

Health outcomes reported in published Arctic cohort studies

associated with exposure to contaminants

Health endpoint Findings Cohort

Cardiovascular

system effects

Hg in cord blood associated with decreased heart rate variability in children at ages 7 and 14 years old

Faroe Islands

Hg in child blood correlated with reduction of heart rate variability Nunavik

Hg was associated with elevated blood pressure among adults Faroe Islands and Nunavik

Endocrine

system effects

Prenatal exposure to high levels of PCBs associated with lower serum testosterone in boys

Faroe Islands

Exposure to PCBs interferes with thyroid hormone homeostasis in adults Hudson River (USA)

The serum POPs have hormone disruptive potentials to ER, AR, and AhR Greenland

Immune system

effects

Serum PCB conc. at 7 years of age positively associated with total immunoglobin E. conc.

Faroe Islands

Parental exposure to OCs increases the susceptibility to infectious diseases Nunavik

OCs strongly, negatively affected serum antibody concentrations during developmental and perinatal exposure

Faroe Islands

Abass et al. 2018 Envi. Sci. Pol. Res.; Weihe et al. 2016 Int J Circumpolar Health

Health outcomes reported in published Arctic cohort studies

associated with exposure to contaminants

Health endpoint Findings Cohort

Nervous system

effects

Postnatal PCB exposure affects information processing at later stages. Arctic Québec

Parental MeHg exposure, up to the age of 22, decreased motor function, verbal ability, memory, and defects in general mental ability

Faroe Islands

Parental exposure to Hg linked to, up to the age of 11, lower estimated IQ, poorer memory functions, and increased risk of attention problems and ADHD behavior

Nunavik

Reproductive

effects

PCB153 strongly correlated with the level of SHBglobulin. Norway

High PCB levels associated with low semen quality in men Faroe Islands

High levels of PFCs in blood were adversely associated with longer menstrual cycles

Greenland, Ukraine

Prenatal exposure to OCs was associated with reduced gestation duration Arctic Quebec

Serum PFC levels were associated significantly with breast cancer risk Greenland

Skeletal system

effects

PCB105 and PCB118 inversely associated with the bone stiffness index Eastern James Bay (Canada)

Abass et al. 2018 Envi. Sci. Pol. Res.; Weihe et al. 2016 Int J Circumpolar Health

Outline









Temporal trends

• To assess the stability

• To examine the impact of regulations

• To provide a firm basis for future levels of pollutants in Arctic

human populations under climate and environmental changes

Abass et al. 2018 Envi. Sci. Pol. Res.

Trends of blood POPs concentrations from same children. Data presented as geometric means. POPs and OCs are in µg/kg plasma lipid.

Trends of POPs in children blood

Data represented as geometric means (µg/kg plasma lipid) for specific locations and periods of time.

Trends of

POPs in

maternal

blood

Data are represented for the specificperiod of samplingPBDE in Finnish breast milk represented PBDE47+PBDE99+PBDE100+PBDE153+PBDE209. TEQ: dioxin toxic equivalents

Trends of POPs in

breast milk samples

Trends of PFCs geometric means (µg/kg plasma lipid) in Yup'ik maternal blood; (µg/kg pooled

blood serum) Swedish first-time mothers and (µg/L whole blood) in Nunavik maternal blood, and

median (ng/ml serum) in men serum sample from Northern Norway. PFOS perfluorooctane sulfonic acid; PFOA perfluooctanoic acid; PFDA Nonadecafluorodecanoic acid

Trends of PFCs in human biological matrices

Outline








- Current-use pesticides

- Per- and polyfluoroalkyl substances

- Brominated flame retardants

- Chlorinated flame retardants

- Organophosphate-based flame retardants and plasticizers

- Siloxanes

- Pharmaceuticals and personal care products

- Polychlorinated naphthalenes

- Hexachlorobutadiene

- Pentachlorophenol (PCP) and pentachloroanisole

- Organotins

- Polycyclic aromatic hydrocarbons

- ‘New’ unintentionally generated PCBs

- Halogenated natural products

- Marine plastics and microplastics

Chemicals of emerging Arctic concern

Still approved to use in USA, Canada and Europe

CUP are essential for efficient and profitable food and livestock production. CUP are only licensed for use if they do not persist in the environment and have low bioaccumulation and short range transport potential

Chemicals of emerging Arctic concern

Outline









- 23% ♂ and 17% ♀ had B-As levels above the ATSDR (1.0 µg/l).

- The B-Pb was 1/8 the CDC toxicological cut-off point of 100 μg/l.

- 47 % of women had a B-Hg higher than 2.0 μg/l; therefore, their

babies could be at risk of adverse effects during development

- B-Cd levels were higher among smokers

- B-Pb levels were elevated among those with higher consumption

of sugar-sweetened soft drinks, smokers, and higher use of alcohol.

- B-Hg levels were elevated among those with higher fish, reindeer

and alcohol consumption.

NFBC

Biomonitoring

Abass et al. 2017 Envi. Sci. Pol. Res.

2016; 75

2. ANSES 20103. CEOH Health Canada; 1994.4. CDC 2010.5. CDC 2012.6. Rice et al. Risk Anal. 20037. Legrand Can. J Health. 20108. Health Canada. 1999. 9. HBM Commission 2003;46.10. HBM Commission 2005;48.12. HBM Commission 1997;40.13. HBM Commission 1999;42.

Biomonitoring

Abass et al. 2016 Int J Circumpolar Health

Abass et al. 2015 AMAP2015 assessment

Meta-analyses

- Environmental epidemiology studies usually include several exposure variables and health related outcomes.

- The number of analyzed outcome variables is important in the statistical analysis and interpretation of research findings

(Maternal exposure to mercury)

Nieminen et al. 2015 Biomed Environ Sci

- Authors often report analyzed health outcome variables based on

their P-values rather than on stated primary research questions.

- This does not help future investigators to know which outcomes are redundant, which provide unique information, and which are most

responsive to changes in the exposure variable.

An elevated number of

outcome variables was

especially found in papers

reporting non-significant associations between

maternal mercury and health

outcomes

Meta-analyses

Problems identified in meta-analysis

Nieminen et al. Chemosphere. 2013;91:131-8). PCBs-secondary sex ratio- Findings were analyzed and reported in many different ways- Results across repeated studies of the same phenomena are rarely identical - The quality of reporting varies: detailed descriptive statistics of the variables,

and standard error for regression coefficients.

Taylor et al. Environ Health Perspect. 2013;121:774-83 - POPs and Type 1&2 diabetes, and childhood obesity with Type 2 diabetes. - Only 43 studies were eligible in their meta-analysis out of 2752 publications. - Too much variation across studies to permit a detailed meta- or pooled analysis.

Singh and coworkers Int J Circumpolar Health. 2014;73:25808- Association between contaminants and health effects in the Arctic. - Difficulties in drawing conclusions included the small number of studies, studies

restricted to a small number of regions, and mixed results.

Meta-analyses

Abass et al. 2016 Int J Circumpolar HealthAbass et al. 2015 AMAP2015 assessment

Toxicokinetic Modelling and future risk prediction

PCB153 in plasma lipids among pregnant women living in Disko Bay, Nuuk and Nunavik during the years 1992–2007.

- HQ is analogous to a margin of exposure, which could be used to estimate the potential to cause harmful effects.- Cancer risk for overall exposure of PCB153 ranged from 2 to 50x10−6 between 1930 to 2050 with higher cancer risk

probability and less than 1 million for the same time period when lower slope factor was applied.

Associated with adverse health effects

Modelled reference daily intakes andproduction trend of PCB153. HQ valuesprovide a basis for estimating potentialnon-cancer adverse effects.

1955 1985

Toxicokinetic Modelling and future risk prediction

Cancer risk probability estimates of thebirth cohorts for pregnant Inuit womenliving in Disko Bay, Nuuk, and Nunavik.

Extrapolated concentrations of PCB153in pregnant Inuit women from Nunavik,Disko Bay and Nuuk. The health risk isestimated by TCP in lipids, BMDL, atwhich it might pose no appreciable riskor minimal risk to human health

Compare the results stemming from the modelling system to those of the detailed semi-quantitative food frequency questioner of the Norwegian Fish & Game Study

(Blood circulation model)

(B⁰(t) organic blood compartment)

Toxicokinetic Modelling vs Food frequency questionnaire

Toxicokinetic modelling based on blood Hg levels gave higher daily intake values of mercury compared to those of the FFQ from the Norwegian Fish & Game Study

FFQ limitations. - Present blood Hg levels indicates Hg exposure several months ago and

participants’ ability to recall their diet correctly may be limited.

- Hg content in food items varies a lot between geographical areas.

- Hg concentrations could be only available for limited food items.

- Increased focus or grouped questions can lead to over-reporting or under-reporting of a particular food items and inaccurate exposure assessment

Toxicokinetic Modelling vs Food frequency questionnaire

hPXRhCAR

XREM

24 structurally diverse pesticides

11 hCYP

Xenbioticcomplex

11 hCYP

Abass et al. 2012, Toxicology. 294: 17–26

Gene regulations and expressions

mRNA 10 µM /fold induction 50 µM /fold induction

CYP1A2 TCDD 218 (10 nM)(20-fold Mela-OH)

Diuron 9 Fold-mRNA 100 Fold-mRNA(IC50 =3 µM)

CYP2B6 Phenobarbital 6 Fold-mRNA(3-fold Bup-OH)

* (500 µM)

Isoproturon 20 Fold-mRNA(7-fold Bup-OH)

22 Fold-mRNA(7-fold Bup-OH)

Atrazine 11 Fold-mRNA(3-fold Bup-OH)

13 Fold-mRNA(4-fold Bup-OH)

CYP3A4 Rifampicin 20 Fold-mRNA(10-fold Tes-6OH)

19 Fold-mRNA(10-fold Tes-6OH)

Fenvalerate 17 Fold-mRNA(3-fold Tes-6OH)


Cyhalothrin 13 Fold-mRNA(5-fold Tes-6OH)


CUP can induce/inhibit the CYPs involved in their own metabolism

mRNA levels in human HepaRG after exposure to CUP

Abass et al. 2013 Toxicol In Vitro. 27(5) 1584-8Abass et al. 2012 Toxicology. 294: 17–26Abass et al. 2009 J. Env. Sci. Health, 44(06), pp. 553 - 563Abass et al. 2007 Drug Metabolism and Disposition 35 1634-1641

10 & 50 µM ?

- Based on the actually measured

chlorpyrifos plasma conc. in

human volunteers

- Pharmacokinetic models of the

environmental exposure to OPs in

U.S. adults, children and

agricultural workers

Gene regulations and expressions

Conclusion

Trends of metals and legacy POPs, except PFCs, are

declining, which indicates the importance of global actions

to reduce emissions of contaminants.

Risk assessment of environmental pollutants requires data

from different sources and methodology, which may form a

part of the multifaceted framework of evidence-based

toxicology leading to a well-documented overall risk

assessment process

The answers to the important questions – how much

contaminants do people acquire in their body during their

whole lifespan and what are the long-term health effects –

require multidisciplinary research and our methods could be

one means of achieving this.

One Arctic – One Health(No. HEL7M0674-65)

contaminants in arctic human populations...contaminants in arctic human populations khaled abass...

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