Perfluoroalkyl substances and immune cell counts in adults from the Mid-Ohio Valley (USA)

Maria Jose Lopez-Espinosa; Christian Carrizosa; Michael I. Luster; Joseph B. Margolick; Olga Costa; Giovanni S. Leonardi; Tony Fletcher

doi:10.1016/j.envint.2021.106599

Perfluoroalkyl substances and immune cell counts in adults from the Mid-Ohio Valley (USA)

Maria Jose Lopez-Espinosa^*, Christian Carrizosa, Michael I. Luster, Joseph B. Margolick, Olga Costa, Giovanni S. Leonardi, Tony Fletcher

^*Corresponding author for this work

Chemicals & Environmental Effects

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

14 Downloads (Pure)

Abstract

Background: Although perfluoroalkyl substances (PFASs) may be immunotoxic, evidence for this in humans is scarce. We studied the association between 4 PFASs (perfluorohexane sulfonate [PFHxS], perfluorooctanoic acid [PFOA], perfluorooctane sulfonate [PFOS] and perfluorononanoic acid [PFNA]) and circulating levels of several types of immune cells.

Methods: Serum PFASs and white blood cell types were measured in 42,782 (2005–2006) and 526 (2010) adults from an area with PFOA drinking water contamination in the Mid-Ohio Valley (USA). Additionally, the major lymphocyte subsets were measured in 2010. Ln(cell counts) and percentages of cell counts were regressed on serum PFAS concentrations (ln or percentiles). Adjusted results were expressed as the percentage difference (95% CI) per interquartile range (IQR) increment of each PFAS concentration.

Results: Generally positive monotonic associations between total lymphocytes and PFHxS, PFOA, and PFOS were found in both surveys (difference range: 1.12–7.33% for count and 0.36–1.77 for percentage, per PFAS IQR increment), and were stronger for PFHxS. These associations were reflected in lymphocyte subset counts but not percentages, with PFHxS positively and monotonically associated with T, B, and natural killer (NK) cell counts (range: 5.51–8.62%), PFOA and PFOS with some T-cell phenotypes, and PFOS with NK cells (range: 3.12–12.21%), the associations being monotonic in some cases. Neutrophils, particularly percentage (range: −1.74 to −0.36), showed decreasing trends associated with PFASs. Findings were less consistent for monocytes and eosinophils.

Conclusion: These results suggest an association between PFHxS and, less consistently, for PFOA and PFOS, and total lymphocytes (although the magnitudes of the differences were small). The increase in absolute lymphocyte count appeared to be evenly distributed across lymphocyte subsets since associations with their percentages were not significant.

Original language	English
Article number	106599
Journal	Environment International
Volume	156
Early online date	13 May 2021
DOIs	https://doi.org/10.1016/j.envint.2021.106599
Publication status	E-pub ahead of print - 13 May 2021

Bibliographical note

Funding Information: This project was funded by the C8 Class Action Settlement Agreement (Circuit Court of Wood County, WV) between DuPont and plaintiffs, which resulted from releases of perfluorooctanoate (PFOA, or C8) into drinking water. It was one of the C8 Science Panel Studies undertaken by the Court-approved C8 Science Panel, of which Dr Tony Fletcher was a member, established under the same Settlement Agreement. Dr Fletcher is a consortium partner of the European Union’s Horizon 2020 research and innovation program under grant agreement 733032 HBM4EU (www.HBM4EU.eu); part-funded by the National
Institute for Health Research (NIHR) Health Protection Research Unit in Environmental Exposures and Health, a partnership between Public Health England, the Health and Safety Executive, and the University of Leicester; and part funded with a PFAS research grant from CORIS/ REGIONE VENETO (Italy). The views expressed are those of the author(s) and not necessarily those of the NIHR, Public Health England, the Health and Safety Executive or the Department of Health and Social Care. MJ Lopez-Espinosa holds grants from the Spanish Carlos III Health
Institute (Miguel Servet-FSE: MSII16/00051 and FIS-FEDER: PI14/ 00891 and PI17/00663), Alicia Koplowitz Foundation 2017, and Ministry of Education, Culture and Sports (Jose Castillejo Grant: CAS17/00052).

Open Access: This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).

Publisher Copyright:© 2021 The Authors. Published by Elsevier Ltd.

Citation: Maria-Jose Lopez-Espinosa, Christian Carrizosa, Michael I. Luster, Joseph B. Margolick, Olga Costa, Giovanni S. Leonardi, Tony Fletcher, Perfluoroalkyl substances and immune cell counts in adults from the Mid-Ohio Valley (USA),
Environment International, Volume 156, 2021, 106599, ISSN 0160-4120.

DOI: https://doi.org/10.1016/j.envint.2021.106599.

Keywords

Immune system
Lymphocytes
PFASs
White blood cells

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Lopez-Espinosa2021PerfluroalkylSubstancesAndImmuneCellCountsEnvironIntFinal published version, 642 KBLicence: CC BY-NC-ND

Cite this

@article{f58eeb52e5774e1c92c7ee4f848ac4f5,

title = "Perfluoroalkyl substances and immune cell counts in adults from the Mid-Ohio Valley (USA)",

abstract = "Background: Although perfluoroalkyl substances (PFASs) may be immunotoxic, evidence for this in humans is scarce. We studied the association between 4 PFASs (perfluorohexane sulfonate [PFHxS], perfluorooctanoic acid [PFOA], perfluorooctane sulfonate [PFOS] and perfluorononanoic acid [PFNA]) and circulating levels of several types of immune cells. Methods: Serum PFASs and white blood cell types were measured in 42,782 (2005–2006) and 526 (2010) adults from an area with PFOA drinking water contamination in the Mid-Ohio Valley (USA). Additionally, the major lymphocyte subsets were measured in 2010. Ln(cell counts) and percentages of cell counts were regressed on serum PFAS concentrations (ln or percentiles). Adjusted results were expressed as the percentage difference (95% CI) per interquartile range (IQR) increment of each PFAS concentration. Results: Generally positive monotonic associations between total lymphocytes and PFHxS, PFOA, and PFOS were found in both surveys (difference range: 1.12–7.33% for count and 0.36–1.77 for percentage, per PFAS IQR increment), and were stronger for PFHxS. These associations were reflected in lymphocyte subset counts but not percentages, with PFHxS positively and monotonically associated with T, B, and natural killer (NK) cell counts (range: 5.51–8.62%), PFOA and PFOS with some T-cell phenotypes, and PFOS with NK cells (range: 3.12–12.21%), the associations being monotonic in some cases. Neutrophils, particularly percentage (range: −1.74 to −0.36), showed decreasing trends associated with PFASs. Findings were less consistent for monocytes and eosinophils. Conclusion: These results suggest an association between PFHxS and, less consistently, for PFOA and PFOS, and total lymphocytes (although the magnitudes of the differences were small). The increase in absolute lymphocyte count appeared to be evenly distributed across lymphocyte subsets since associations with their percentages were not significant.",

keywords = "Immune system, Lymphocytes, PFASs, White blood cells",

author = "Lopez-Espinosa, {Maria Jose} and Christian Carrizosa and Luster, {Michael I.} and Margolick, {Joseph B.} and Olga Costa and Leonardi, {Giovanni S.} and Tony Fletcher",

note = "Funding Information: This project was funded by the C8 Class Action Settlement Agreement (Circuit Court of Wood County, WV) between DuPont and plaintiffs, which resulted from releases of perfluorooctanoate (PFOA, or C8) into drinking water. It was one of the C8 Science Panel Studies undertaken by the Court-approved C8 Science Panel, of which Dr Tony Fletcher was a member, established under the same Settlement Agreement. Dr Fletcher is a consortium partner of the European Union{\textquoteright}s Horizon 2020 research and innovation program under grant agreement 733032 HBM4EU (www.HBM4EU.eu); part-funded by the National Institute for Health Research (NIHR) Health Protection Research Unit in Environmental Exposures and Health, a partnership between Public Health England, the Health and Safety Executive, and the University of Leicester; and part funded with a PFAS research grant from CORIS/ REGIONE VENETO (Italy). The views expressed are those of the author(s) and not necessarily those of the NIHR, Public Health England, the Health and Safety Executive or the Department of Health and Social Care. MJ Lopez-Espinosa holds grants from the Spanish Carlos III Health Institute (Miguel Servet-FSE: MSII16/00051 and FIS-FEDER: PI14/ 00891 and PI17/00663), Alicia Koplowitz Foundation 2017, and Ministry of Education, Culture and Sports (Jose Castillejo Grant: CAS17/00052). Open Access: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Publisher Copyright:{\textcopyright} 2021 The Authors. Published by Elsevier Ltd. Citation: Maria-Jose Lopez-Espinosa, Christian Carrizosa, Michael I. Luster, Joseph B. Margolick, Olga Costa, Giovanni S. Leonardi, Tony Fletcher, Perfluoroalkyl substances and immune cell counts in adults from the Mid-Ohio Valley (USA), Environment International, Volume 156, 2021, 106599, ISSN 0160-4120. DOI: https://doi.org/10.1016/j.envint.2021.106599.",

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TY - JOUR

T1 - Perfluoroalkyl substances and immune cell counts in adults from the Mid-Ohio Valley (USA)

AU - Lopez-Espinosa, Maria Jose

AU - Carrizosa, Christian

AU - Luster, Michael I.

AU - Margolick, Joseph B.

AU - Costa, Olga

AU - Leonardi, Giovanni S.

AU - Fletcher, Tony

N1 - Funding Information: This project was funded by the C8 Class Action Settlement Agreement (Circuit Court of Wood County, WV) between DuPont and plaintiffs, which resulted from releases of perfluorooctanoate (PFOA, or C8) into drinking water. It was one of the C8 Science Panel Studies undertaken by the Court-approved C8 Science Panel, of which Dr Tony Fletcher was a member, established under the same Settlement Agreement. Dr Fletcher is a consortium partner of the European Union’s Horizon 2020 research and innovation program under grant agreement 733032 HBM4EU (www.HBM4EU.eu); part-funded by the National Institute for Health Research (NIHR) Health Protection Research Unit in Environmental Exposures and Health, a partnership between Public Health England, the Health and Safety Executive, and the University of Leicester; and part funded with a PFAS research grant from CORIS/ REGIONE VENETO (Italy). The views expressed are those of the author(s) and not necessarily those of the NIHR, Public Health England, the Health and Safety Executive or the Department of Health and Social Care. MJ Lopez-Espinosa holds grants from the Spanish Carlos III Health Institute (Miguel Servet-FSE: MSII16/00051 and FIS-FEDER: PI14/ 00891 and PI17/00663), Alicia Koplowitz Foundation 2017, and Ministry of Education, Culture and Sports (Jose Castillejo Grant: CAS17/00052). Open Access: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Publisher Copyright:© 2021 The Authors. Published by Elsevier Ltd. Citation: Maria-Jose Lopez-Espinosa, Christian Carrizosa, Michael I. Luster, Joseph B. Margolick, Olga Costa, Giovanni S. Leonardi, Tony Fletcher, Perfluoroalkyl substances and immune cell counts in adults from the Mid-Ohio Valley (USA), Environment International, Volume 156, 2021, 106599, ISSN 0160-4120. DOI: https://doi.org/10.1016/j.envint.2021.106599.

PY - 2021/5/13

Y1 - 2021/5/13

N2 - Background: Although perfluoroalkyl substances (PFASs) may be immunotoxic, evidence for this in humans is scarce. We studied the association between 4 PFASs (perfluorohexane sulfonate [PFHxS], perfluorooctanoic acid [PFOA], perfluorooctane sulfonate [PFOS] and perfluorononanoic acid [PFNA]) and circulating levels of several types of immune cells. Methods: Serum PFASs and white blood cell types were measured in 42,782 (2005–2006) and 526 (2010) adults from an area with PFOA drinking water contamination in the Mid-Ohio Valley (USA). Additionally, the major lymphocyte subsets were measured in 2010. Ln(cell counts) and percentages of cell counts were regressed on serum PFAS concentrations (ln or percentiles). Adjusted results were expressed as the percentage difference (95% CI) per interquartile range (IQR) increment of each PFAS concentration. Results: Generally positive monotonic associations between total lymphocytes and PFHxS, PFOA, and PFOS were found in both surveys (difference range: 1.12–7.33% for count and 0.36–1.77 for percentage, per PFAS IQR increment), and were stronger for PFHxS. These associations were reflected in lymphocyte subset counts but not percentages, with PFHxS positively and monotonically associated with T, B, and natural killer (NK) cell counts (range: 5.51–8.62%), PFOA and PFOS with some T-cell phenotypes, and PFOS with NK cells (range: 3.12–12.21%), the associations being monotonic in some cases. Neutrophils, particularly percentage (range: −1.74 to −0.36), showed decreasing trends associated with PFASs. Findings were less consistent for monocytes and eosinophils. Conclusion: These results suggest an association between PFHxS and, less consistently, for PFOA and PFOS, and total lymphocytes (although the magnitudes of the differences were small). The increase in absolute lymphocyte count appeared to be evenly distributed across lymphocyte subsets since associations with their percentages were not significant.

AB - Background: Although perfluoroalkyl substances (PFASs) may be immunotoxic, evidence for this in humans is scarce. We studied the association between 4 PFASs (perfluorohexane sulfonate [PFHxS], perfluorooctanoic acid [PFOA], perfluorooctane sulfonate [PFOS] and perfluorononanoic acid [PFNA]) and circulating levels of several types of immune cells. Methods: Serum PFASs and white blood cell types were measured in 42,782 (2005–2006) and 526 (2010) adults from an area with PFOA drinking water contamination in the Mid-Ohio Valley (USA). Additionally, the major lymphocyte subsets were measured in 2010. Ln(cell counts) and percentages of cell counts were regressed on serum PFAS concentrations (ln or percentiles). Adjusted results were expressed as the percentage difference (95% CI) per interquartile range (IQR) increment of each PFAS concentration. Results: Generally positive monotonic associations between total lymphocytes and PFHxS, PFOA, and PFOS were found in both surveys (difference range: 1.12–7.33% for count and 0.36–1.77 for percentage, per PFAS IQR increment), and were stronger for PFHxS. These associations were reflected in lymphocyte subset counts but not percentages, with PFHxS positively and monotonically associated with T, B, and natural killer (NK) cell counts (range: 5.51–8.62%), PFOA and PFOS with some T-cell phenotypes, and PFOS with NK cells (range: 3.12–12.21%), the associations being monotonic in some cases. Neutrophils, particularly percentage (range: −1.74 to −0.36), showed decreasing trends associated with PFASs. Findings were less consistent for monocytes and eosinophils. Conclusion: These results suggest an association between PFHxS and, less consistently, for PFOA and PFOS, and total lymphocytes (although the magnitudes of the differences were small). The increase in absolute lymphocyte count appeared to be evenly distributed across lymphocyte subsets since associations with their percentages were not significant.

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KW - Lymphocytes

KW - PFASs

KW - White blood cells

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Perfluoroalkyl substances and immune cell counts in adults from the Mid-Ohio Valley (USA)

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Keywords

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