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BEDREHELSE-Bedre helse og livskvalitet

Immunotoxic effects of prenatal and childhood exposure to perfluoroalkyl substances

Awarded: NOK 5.5 mill.

Project Number:

228195

Application Type:

Project Period:

2013 - 2019

Partner countries:

The environmental pollutants perfluoroalkyl substances (PFASs) are ubiquitously distributed in wildlife, and studies have shown that the PFASs can cross the human placenta and reach the foetus. In our birth cohort BraMat, prenatal exposure to PFASs was associated with a reduced vaccination response to the rubella vaccine in the children at three years of age. Furthermore, a positive association between prenatal exposure to PFASs and the number of episodes of common cold and gastroenteritis was found. These findings suggest that prenatal exposure to various PFASs may lead to immunosuppression in early childhood. The primary objective of the present project was to bring forth knowledge on immunotoxic effects of prenatal and childhood exposure to PFASs. This was achieved by the use of data from three existing birth cohorts: BraMat (0-3 years), the Norwegian Mother and Child Cohort Study (MoBa; 0-7 yrs) and the Environment and Childhood Study (ECA; 0-16 yrs). Gene expression data was used to elucidate possible biomarkers of exposure and molecular pathways important for the immunotoxic effects of PFASs. Ontology and CoPub were used to investigate gene-function relations for genes correlating with both PFAS exposure and the health outcomes common cold and/or rubella vaccination titres. Genes associated with PFAS exposure showed enrichment for immunological and developmental functions. Our analyses identified a toxicogenomics profile of PFAS exposure-associated genes that were in common with genes associated with rubella titers and/or common cold episodes, including several immunomodulatory genes as well as other immune-associated genes (Pennings et al. J Immunotoxicol 2016;13:173-180). These findings provides a transcriptomics connection between prenatal PFAS exposure and impaired immune function in early childhood. In 2016-2017, the postdoctoral fellow had a research stay at the National Institute of Environmental Health Sciences (NIEHS). The Group at NIEHS has extensive experience working with the MoBa database as well as expertise on epidemiological methods. The postdoctoral fellow has benefited from this knowledge in his statistical analyses of the MoBa-cohort and manuscript preparations. Using the MoBa-study, we found an inverse association between prenatal exposure to perfluoroundecanoic acid (PFUnDA) and eczema, as well as a positive association between PFASs and infectious diseases such as bronchitis/pneumonia, throat infections and gastric flu up to the ages 3 and/or 7 years (Impinen et al. Environ Int 2019;124:462-472). Our results also indicate a possible role of gender in the PFAS-health outcome associations. In the ECA-study, we observed that although prenatal exposure to PFASs was not associated with atopic or lung manifestations by 10 years of age, several PFASs were associated with an increased number of respiratory tract infections in the first 10 years of life, suggesting immunosuppressive effects of PFASs (Impinen et al. Environ Res 2018;160:518-523). Thus, our studies give further supporting evidence for immunosuppressive effects of prenatal exposure to PFASs. In the ECA-study, we have also studied possible effects of PFAS exposure during childhood on airways infections and asthma- and allergy-related outcomes by measuring PFASs in 10 years old children and examined associations with the health outcomes at 10-16 years of age (Kvalem et al, submitted, March 2019).

Resultatene fra PFAS-ImmTox prosjektet har blitt brukt som en del av grunnlaget for en Monograph på PFOS og PFOA fra National Toxicology Program, USA. I tillegg er resultatene brukt som støttegrunnlag i en risikovurdering av PFOS og PFOA utført av det europeiske mattrygghetsorganet EFSA. I EFSAs risikovurdering anbefales nye grenseverdier som er 80 og 1750 ganger lavere enn dagens grenseverdier (fra 2008) for henholdsvis PFOS og PFOA. Resultatene fra prosjektet har vakt internasjonal interesse og gir ytterligere evidens for immunhemmende effekter av prenatal eksponering for PFASs.

The immune system develops extensively during the foetal stage which makes the foetus especially vulnerable to environmental exposures. Alteration in the immune system due to early life exposure to immunotoxic compounds may result in long-lasting chronic disease for the individual, accompanied with considerable socioeconomic consequences. The environmental pollutants perfluoroalkyl substances (PFAS) are ubiquitously distributed in wildlife, and studies have shown that the PFAS can cross the human placenta and reach the foetus. In our birth cohort BraMat, prenatal exposure to PFAS was inversely correlated with the vaccination responses in the children at three years of age. Furthermore, a positive association between prenatal exposure to PFAS and number of episodes of gastroenteritis and upper respiratory tract infections in the child was found. These results suggest that prenatal exposure to various PFAS may lead to immunosuppression in early childhood, and illustrate the necessity for further investigati ons of the immunotoxic potential of PFAS. The primary objective of the present proposal is to bring forth knowledge on immunotoxic effects of prenatal and childhood exposures to PFAS. This will be achieved by the use of data from three existing birth coho rts: BraMat (0-3 years), the Norwegian Mother and Child Cohort Study (MoBa; 0-7 years) and the Environment and Childhood Asthma study (ECA; 0-16 years). Gene expression data will be used to elucidate possible biomarkers of exposure and molecular pathways important for the immunotoxic effects of PFAS. Integration of the results from this project will contribute to the risk assessment concerning prenatal and childhood exposure of PFAS.

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Funding scheme:

BEDREHELSE-Bedre helse og livskvalitet