{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T10:42:01Z","timestamp":1780656121805,"version":"3.54.1"},"reference-count":40,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"North Carolina General Assembly:North Carolina Policy Collaboratory","award":["668910"],"award-info":[{"award-number":["668910"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Toxics"],"abstract":"<jats:p>Novel per- and polyfluoroalkyl substances (PFAS) were recently identified in drinking water sources throughout North Carolina. These include the perfluoroether acids (PFEAs) perfluoro-2-methoxyacetic acid (PFMOAA), perfluoro-2-methoxypropanoic acid (PFMOPrA), and perfluoro-4-methoxybutanioc acid (PFMOBA). Little toxicological data exist for these PFEAs. Therefore, the present study described signs of toxicity and immunotoxicity following oral exposure. Adult male and female C57BL\/6 mice were exposed once\/day for 30 days to PFMOAA (0, 0.00025, 0.025, or 2.5 mg\/kg), PFMOPrA, or PFMOBA (0, 0.5, 5, or 50 mg\/kg). A dose of 7.5 mg\/kg of perfluorooctanoic acid (PFOA) was used as a positive control. Terminal body weights, and absolute liver, spleen, or thymus weights did not differ by dose for any compound; exposure to 50 mg\/kg of PFMOBA increased relative liver weights in males. Changes in splenic cellularity were observed in males exposed to PFMOPrA and decreased numbers of B and natural killer (NK) cells were observed in males and females exposed to PFMOBA. Exposure did not alter NK cell cytotoxicity or T cell-dependent antibody responses at doses administered. Our results indicate that these \u201cunderstudied\u201d PFAS have toxicological potential but require additional investigation across endpoints and species, including humans, to understand health effects via drinking water exposure.<\/jats:p>","DOI":"10.3390\/toxics9050100","type":"journal-article","created":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T21:35:39Z","timestamp":1619904939000},"page":"100","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Immunotoxicity of Per- and Polyfluoroalkyl Substances: Insights into Short-Chain PFAS Exposure"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6980-8898","authenticated-orcid":false,"given":"Tracey","family":"Woodlief","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Vance","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"DeWitt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.ecoenv.2019.02.058","article-title":"Occurrence, sources and health risk of polyfluoroalkyl substances (PFASs) in soil, water and sediment from a drinking water source area","volume":"174","author":"Cao","year":"2019","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_2","unstructured":"(2021, April 18). No TiPFAS|EPA: PFAS structures in DSSTox, Available online: https:\/\/comptox.epa.gov\/dashboard\/chemical_lists\/PFASSTRUCT.Published."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s00204-009-0424-0","article-title":"Chronic effects of perfluorooctanesulfonate exposure on immunotoxicity in adult male C57BL\/6 mice","volume":"83","author":"Dong","year":"2009","journal-title":"Arch. Toxicol."},{"key":"ref_4","unstructured":"(CDC) C for DC (2021, April 18). Fourth Report Executive Summary, Available online: https:\/\/www.cdc.gov\/exposurereport\/pdf\/FourthReport_ExecutiveSummary.pdf."},{"key":"ref_5","unstructured":"ATSDR\/CDC, Agency for Toxic Substances and Disease Registry (2021, April 18). ATSDR-Toxicological Profile: Perfluoroalkyls. Toxic Subst Portal, Available online: https:\/\/www.atsdr.cdc.gov\/toxprofiles\/tp.asp?id=671&tid=124%0Ahttps:\/\/www.atsdr.cdc.gov\/toxprofiles\/tp.asp?id=1117&tid=237."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.envpol.2018.07.042","article-title":"Associations between longitudinal serum perfluoroalkyl substance (PFAS) levels and measures of thyroid hormone, kidney function, and body mass index in the Fernald Community Cohort","volume":"242","author":"Blake","year":"2018","journal-title":"Environ. Pollut."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.chroma.2018.03.047","article-title":"Validation of quantitative measurements and semi-quantitative estimates of emerging perfluoroethercarboxylic acids (PFECAs) and hexfluoroprolyene oxide acids (HFPOAs)","volume":"1551","author":"McCord","year":"2018","journal-title":"J. Chromatogr. A"},{"key":"ref_8","unstructured":"(2021, April 18). Home-North Carolina Policy Collaboratory. Available online: https:\/\/collaboratory.unc.edu\/."},{"key":"ref_9","unstructured":"(2021, April 18). What Is the NC PFAST Network NC PFAS Testing Network. Available online: https:\/\/ncpfastnetwork.com\/."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/awwa.1073","article-title":"Recently Detected Drinking Water Contaminants: GenX and Other Per- and Polyfluoroalkyl Ether Acids","volume":"110","author":"Hopkins","year":"2018","journal-title":"J. Am. Water Work. Assoc."},{"key":"ref_11","first-page":"112","article-title":"Perspectives | Brief Communication Fluorotechnology Is Critical to Modern Life: The FluoroCouncil Counterpoint to the Madrid Statement","volume":"5","author":"Bowman","year":"2015","journal-title":"Environ Health Perspect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.envint.2018.01.011","article-title":"Comparing the toxic potency in vivo of long-chain perfluoroalkyl acids and fluorinated alternatives","volume":"113","author":"Gomis","year":"2018","journal-title":"Environ. Int."},{"key":"ref_13","first-page":"179","article-title":"Evaluation of the immunomodulatory effects of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate in C57BL\/6 mice","volume":"156","author":"Rushing","year":"2017","journal-title":"Toxicol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1038\/s41590-018-0251-7","article-title":"Metabolic reprogramming of natural killer cells in obesity limits antitumor responses","volume":"19","author":"Michelet","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1021\/acs.est.6b04806","article-title":"A Never-Ending Story of Per- and Polyfluoroalkyl Substances (PFASs)?","volume":"51","author":"Wang","year":"2017","journal-title":"Environ. Sci. Technol."},{"key":"ref_16","unstructured":"National Toxicology Program (2016). Monograph on Immunotoxicity Associated with Exposure to Perfluorooctanoic Acid or Perfluorooctane Sulfonate."},{"key":"ref_17","unstructured":"USEPA (1996). Health Effects Test Guidelines: OPPTS 870.7880 Immunotoxicity."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1289\/ehp.10896","article-title":"Perfluorooctanoic Acid\u2013Induced Immunomodulation in Adult C57BL\/6J or C57BL\/6N Female Mice","volume":"116","author":"DeWitt","year":"2008","journal-title":"Environ. Health Perspect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/S0006-2952(01)00752-3","article-title":"Further evidence for the involvement of inhibition of cell proliferation and development in thymic and splenic atrophy induced by the peroxisome proliferator perfluoroctanoic acid in mice33Abbreviations: PFOA, perfluorooctanoic acid; PP, peroxisome proliferator; FBS, fetal bovine serum; FITC, fluorescein isothiocyanate; and DEHP, di(2-ethylhexyl)phthalate","volume":"62","author":"Yang","year":"2001","journal-title":"Biochem. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1016\/S0006-2952(02)00923-1","article-title":"Involvement of the peroxisome proliferator-activated receptor alpha in the immunomodulation caused by peroxisome proliferators in mice","volume":"63","author":"Yang","year":"2002","journal-title":"Biochem. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1093\/toxsci\/kfaa138","article-title":"Immunotoxicity of an Electrochemically Fluorinated Aqueous Film-Forming Foam","volume":"178","author":"Ward","year":"2020","journal-title":"Toxicol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41370-018-0097-y","article-title":"Exposure to per-fluoroalkyl and polyfluoroalkyl substances leads to immunotoxicity: Epidemiological and toxicological evidence","volume":"29","author":"DeWitt","year":"2019","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/0304-4165(86)90211-4","article-title":"Determination of peroxisomal fatty acyl-CoA oxidase activity using a lauroyl-CoA-based fluorometric assay","volume":"884","author":"Poosch","year":"1986","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3109\/1547691X.2014.996682","article-title":"Suppression of antigen-specific antibody responses in mice exposed to perfluorooctanoic acid: Role of PPAR\u03b1and T- and B-cell targeting","volume":"13","author":"DeWitt","year":"2016","journal-title":"J. Immunotoxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.yrtph.2014.02.008","article-title":"The T-cell-dependent antibody response assay in nonclinical studies of pharmaceuticals and chemicals: Study design, data analysis, interpretation","volume":"69","author":"Lebrec","year":"2014","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/etc.4890","article-title":"Per- and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research","volume":"40","author":"Fenton","year":"2021","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41370-018-0094-1","article-title":"A review of the pathways of human exposure to poly- and perfluoroalkyl substances (PFASs) and present understanding of health effects","volume":"29","author":"Sunderland","year":"2019","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1001\/jama.2011.2034","article-title":"Serum Vaccine Antibody Concentrations in Children Exposed to Perfluorinated Compounds","volume":"307","author":"Grandjean","year":"2012","journal-title":"JAMA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.envint.2016.08.026","article-title":"Association between prenatal exposure to perfluorinated compounds and symptoms of infections at age 1\u20134years among 359 children in the Odense Child Cohort","volume":"96","author":"Dalsager","year":"2016","journal-title":"Environ. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1080\/1547691X.2017.1360968","article-title":"Estimated exposures to perfluorinated compounds in infancy predict attenuated vaccine antibody concentrations at age 5-years","volume":"14","author":"Grandjean","year":"2017","journal-title":"J. Immunotoxicol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"077018","DOI":"10.1289\/EHP275","article-title":"Serum Vaccine Antibody Concentrations in Adolescents Exposed to Perfluorinated Compounds","volume":"125","author":"Grandjean","year":"2017","journal-title":"Environ. Health Perspect."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"106395","DOI":"10.1016\/j.envint.2021.106395","article-title":"Exposure to perfluoroalkyl substances during fetal life and hospitalization for infectious disease in childhood: A study among 1,503 children from the Odense Child Cohort","volume":"149","author":"Dalsager","year":"2021","journal-title":"Environ. Int."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Liu, G., Dhana, K., Furtado, J.D., Rood, J., Zong, G., Liang, L., Qi, L., Bray, G.A., DeJonge, L., and Coull, B. (2018). Perfluoroalkyl substances and changes in body weight and resting metabolic rate in response to weight-loss diets: A prospective study. PLoS Med., 15.","DOI":"10.1371\/journal.pmed.1002502"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3109\/1547691X.2012.755580","article-title":"Pre-natal exposure to perfluoroalkyl substances may be associated with altered vaccine antibody levels and immune-related health outcomes in early childhood","volume":"10","author":"Granum","year":"2012","journal-title":"J. Immunotoxicol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1093\/toxsci\/kfn059","article-title":"Suppression of Humoral Immunity in Mice following Exposure to Perfluorooctane Sulfonate","volume":"104","author":"Keller","year":"2008","journal-title":"Toxicol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s00204-008-0361-3","article-title":"Immunotoxic changes associated with a 7-day oral exposure to perfluorooctanesulfonate (PFOS) in adult male C57BL\/6 mice","volume":"83","author":"Zheng","year":"2008","journal-title":"Arch. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.envint.2016.11.014","article-title":"Molecular mechanisms of PFOA-induced toxicity in animals and humans: Implications for health risks","volume":"99","author":"Li","year":"2017","journal-title":"Environ. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1289\/ehp.0901827","article-title":"Epidemiologic Evidence on the Health Effects of Perfluorooctanoic Acid (PFOA)","volume":"118","author":"Steenland","year":"2010","journal-title":"Environ. Health Perspect."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1007\/s00204-018-2181-4","article-title":"Perfluorooctanoic acid (PFOA) exposure promotes proliferation, migration and invasion potential in human breast epithelial cells","volume":"92","author":"Pierozan","year":"2018","journal-title":"Arch. Toxicol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1046\/j.1365-2249.2000.01367.x","article-title":"Effects of peroxisome proliferators on the thymus and spleen of mice","volume":"122","author":"Yang","year":"2000","journal-title":"Clin. Exp. Immunol."}],"updated-by":[{"DOI":"10.3390\/toxics11080656","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000}}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/9\/5\/100\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T23:10:38Z","timestamp":1754262638000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/9\/5\/100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,1]]},"references-count":40,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["toxics9050100"],"URL":"https:\/\/doi.org\/10.3390\/toxics9050100","relation":{"correction":[{"id-type":"doi","id":"10.3390\/toxics11080656","asserted-by":"object"}]},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,1]]}}}