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Meta-Analysis
. 2022 Apr;130(4):46001.
doi: 10.1289/EHP10092. Epub 2022 Apr 27.

Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis

Elizabeth Costello  1 , Sarah Rock  1 , Nikos Stratakis  1 , Sandrah P Eckel  1 , Douglas I Walker  2 , Damaskini Valvi  2 , Dora Cserbik  3 , Todd Jenkins  4 , Stavra A Xanthakos  5 , Rohit Kohli  6 , Stephanie Sisley  7 , Vasilis Vasiliou  8 , Michele A La Merrill  9 , Hugo Rosen  10 , David V Conti  1 , Rob McConnell  1 , Leda Chatzi  1
Affiliations
Meta-Analysis

Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis

Elizabeth Costello et al. Environ Health Perspect. 2022 Apr.

Abstract

Background: Experimental evidence indicates that exposure to certain pollutants is associated with liver damage. Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals widely used in industry and consumer products and bioaccumulate in food webs and human tissues, such as the liver.

Objective: The objective of this study was to conduct a systematic review of the literature and meta-analysis evaluating PFAS exposure and evidence of liver injury from rodent and epidemiological studies.

Methods: PubMed and Embase were searched for all studies from earliest available indexing year through 1 December 2021 using keywords corresponding to PFAS exposure and liver injury. For data synthesis, results were limited to studies in humans and rodents assessing the following indicators of liver injury: serum alanine aminotransferase (ALT), nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, or steatosis. For human studies, at least three observational studies per PFAS were used to conduct a weighted z-score meta-analysis to determine the direction and significance of associations. For rodent studies, data were synthesized to qualitatively summarize the direction and significance of effect.

Results: Our search yielded 85 rodent studies and 24 epidemiological studies, primarily of people from the United States. Studies focused primarily on legacy PFAS: perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid. Meta-analyses of human studies revealed that higher ALT levels were associated with exposure to PFOA (z-score= 6.20, p<0.001), PFOS (z-score= 3.55, p<0.001), and PFNA (z-score= 2.27, p=0.023). PFOA exposure was also associated with higher aspartate aminotransferase and gamma-glutamyl transferase levels in humans. In rodents, PFAS exposures consistently resulted in higher ALT levels and steatosis.

Conclusion: There is consistent evidence for PFAS hepatotoxicity from rodent studies, supported by associations of PFAS and markers of liver function in observational human studies. This review identifies a need for additional research evaluating next-generation PFAS, mixtures, and early life exposures. https://doi.org/10.1289/EHP10092.

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Figures

Figure 1 is a flowchart has five steps. Step 1: There are 881 potentially relevant articles, including 371 PubMed, 510 Embase, and 205 duplicated articles were excluded. Step 2: There are 676 Articles for screening based on title and or abstract, 2 articles identified from reviews, and 440 did not meet inclusion criteria. Step 3: 236 articles for screening based on full text and 125 did not meet inclusion criteria. Step 4: 111 articles included for data extraction leads to 25 human studies articles and 86 animal studies articles.
Figure 1.
Flow chart of the study selection.
Figure 2 is a set of two strip plots. The first strip plot, plotting reference, species, strain (sex), exposure route, exposure, duration, and sample collection, including (bottom to top) Marques and others (reference 130), Mice, C D -1 (M), Prenatal, P F O A plus H F D, G D 1 -P N D 21, P N D 90; Marques and others (reference 130), Mice, C D -1 (M), Prenatal, P F O A, G D 1 -P N D 21, P N D 90; Marques and others (reference 130), Mice, C D -1 (F), Prenatal, P F O A plus H F D, G D 1 -P N D 21, P N D 90; Marques and others (reference 130), Mice, C D -1 (F), Prenatal, P F O A, G D 1 -P N D 21, P N D 90; Marques and others (reference 130), Mice, C D -1 (M F), Prenatal, P F O A plus H F D, G D 1 -P N D 21, EOT; Marques and others (reference 130), Mice, C D -1 (M F), Prenatal, P F O A, G D 1 -P N D 21, EOT; Quist and others (reference 106), Mice, C D -1 (F), Prenatal, P F O A plus H F D, G D 1 -17 P N D 91 (M F); Quist and others (reference 106), Mice, C D -1 (F), Prenatal, P F O A plus H F D, G D 1 -17 P N D 91 (F); Quist and others (reference 106), Mice, C D -1 (F), Prenatal, P F O A plus L F D, G D 1 -17 P N D 91; Quist and others (reference 106), Mice, C D -1 (F), Prenatal, P F O A, G D 1 -17 P N D 91; Li D and others (reference 86), Mice, Kunming (F), Prenatal, P F O A, G D 1 -17, and P N D 91; Shao and others (reference 172), Mice, I C R (M), Prenatal, P F O A, G D 13 -17, and P N Week 12; Pouwer and others (reference 87), Mice, A P O E asterisk 3 -Leiden C E T P (M), Diet, P F O A, 4 W, and E O T; Pouwer and others (reference 87), Mice, A P O E asterisk 3 -Leiden C E T P (M), Diet, P F O A, 6 W, and E O T; Pouwer and others (reference 87), Mice, A P O E asterisk 3 -Leiden C E T P (M), Diet, P F O A, 6 W, and Week 4; Cui and others (reference 170), Mice, miR -34 a (negative negative) C 5 7 B L 6 J (M), Gavage, P F O A, 28 D, and E O T; Cui and others (reference 170), C 57 B L 6 J (M), Gavage, P F O A, 28 D, and E O T; Wang and others (reference 109), C 57 B L 6 J (M), Gavage, P F O A, 30 D, and E O T; Wang and others (reference 109), C 57 B L 6 J (M), Gavage, P F O A, 15 D, and E O T; Shi and others (reference 173), Mice, C 57 B L 6 J (M), Gavage, P F O A plus LaoLao2, 1 D, and E O T; Shi and others (reference 173), Mice, C 57 B L 6 J (M), Gavage, P F O A plus LaoLao1, 1 D, and E O T; Shi and others (reference 173), Mice, C 57 B L 6 J (M), Gavage, P F O A plus LaoHad2, 1 D, and E O T; Shi and others (reference 173), Mice, C 57 B L 6 J (M), Gavage, P F O A plus LaoHao1, 1 D, and E O T; Shi and others (reference 173), Mice, C 57 B L 6 J (M), Gavage, P F O A plus HaoLad2, 1 D, and E O T; Shi and others (reference 173), Mice, C 57 B L 6 J (M), Gavage, P F O A plus HaoLad1, 1 D, and E O T; Shi and others (reference 173), Mice, C 57 B L 6 J (M), Gavage, P F O A plus HaoHad2, 1 D, and E O T; Shi and others (reference 173), Mice, C 57 B L 6 J (M), Gavage, P F O A plus HaoHad1, 1 D, and E O T; Shi and others (reference 173), Mice, C 57 B L 6 J (M), Gavage, P F O A plus Que, 1 D, and E O T; Shi and others (reference 173), Mice, C 57 B L 6 J (M), Gavage, P F O A, 1 D, and E O T; Crebelli and others (reference 82), Mice, C 57 B L 6 (M), Water, P F O A, 5 W, and E O T; Li and others (reference 102), Mice, C 57 B L 6 (M), Gavage, P F O A plus H F D, 2 W, and E O T; Li and others (reference 102), Mice, C 57 B L 6 (M), Gavage, P F O A plus H F D, 8 W, and E O T; Li and others (reference 102), Mice, C 57 B L 6 (M), Gavage, P F O A plus H F D, 16 W, and E O T; Li and others (reference 102), Mice, C 57 B L 6 (M), Gavage, P F O A plus L F D, 2 W, and E O T; Li and others (reference 102), Mice, C 57 B L 6 (M), Gavage, P F O A plus L F D, 8 W, and E O T; Li and others (reference 102), Mice, C 57 B L 6 (M), Gavage, P F O A plus L F D, 16 W, and E O T; Tan and others (reference 108), Mice, C 57 B L 6 N (M), Diet, P F O A plus H F D, 3 W, and E O T; Tan and others (reference 108), Mice, C 57 B L 6 N (M), Diet, P F O A, 3 W, and E O T; Blake and others (reference 81), Mice, C D -1 (Dams), Gavage, P F O A, E 1.5 to E 11.5, and E 11.5; Blake and others (reference 81), Mice, C D -1 (Dams), Gavage, P F O A, E 1.5 to E 11.5, and E 17.5; Marques and others (reference 130), Mice, CD -1 (Dams), Gavage, P F O A plus H F D, G D 1 to P N D 21, and E O T; Marques and others (reference 130), Mice, CD -1 (Dams), Gavage, P F O A, G D 1 to P N D 21, and E O T; Hui and others (reference 85), Mice, B A L B c (M), Gavage, P F O A, 7 D, and E O T; Yan and others (reference 175), Mice, B A L B c (M), Gavage, P F O A plus 4-P B A 250, 28 D, and E O T; Yan and others (reference 175), Mice, B A L B c (M), Gavage, P F O A plus 4-P B A 125, 28 D, and E O T; Yan and others (reference 175), Mice, B A L B c (M), Gavage, P F O A, 28 D, and E O T; Guo and others (reference 171), Mice, B A L B c (M), Gavage, P F O A, 28 D, and E O T; Guo and others (reference 84), Mice, B A L B c (M), Gavage, P F O A, 28 D, and E O T; Yan and others (reference 89), Mice, B A L B c (M), Gavage, P F O A, 28 D, and E O T; Liu and others (reference 103), Mice, Kunming (M), Gavage, P F O A plus G S P E, 14 D, and E O T; Liu and others (reference 103), Mice, Kunming (M), Gavage, P F O A, 14 D, and E O T; Zou and others (reference 111), Mice, Kunming (M), Gavage, P F O A plus Que, 15 D, and E O T; Zou and others (reference 111), Mice, Kunming (M), Gavage, P F O A, 14 D, and E O T; Wu and others (reference 91), Mice, Kunming (M), Gavage, P F O A, 21 D, and E O T; Wu and others (reference 174), Mice, Kunming (M), Gavage, P F O A, 1 D, and E O T; Yang and others (reference 110), Mice, Kunming (M), Gavage, P F O A, 14 D, and E O T; Yahia and others (reference 88), Mice, I C R (Dams), Gavage, P F O A, G D 0 to G D 17, and E O T; Minata and others (reference 96), Mice, P P A R lowercase alpha-null (M), Gavage, P F O A, 4 W, and E O T; Nakagawa and others (reference 97), Mice, P P A R lowercase alpha-null (M), Gavage, P F O A, 6 W, and E O T; Nakagawa and others (reference 97), Mice, h P P A R lowercase alpha-null (M), Gavage, P F O A, 6 W, and E O T; Nakagawa and others (reference 97), Mice, m P P A R lowercase alpha-null (M), Gavage, P F O A, 6 W, and E O T; Minata and others (reference 96), Mice, 129 S 4 or Svlm J (M), Gavage, P F O A, 4 W, and E O T; Owumi and others (reference 112), Rats, Wistar (M), Gavage, P F O A plus N A C 50, 28 D, and E O T; Owumi and others (reference 112), Rats, Wistar (M), Gavage, P F O A plus N A C 25, 28 D, and E O T; Owumi and others (reference 112), Rats, Wistar (M), Gavage, P F O A, 28 D, and E O T; Butenhoff and others (reference 93), Rats, S D (F), Gavage, P F O A, 28 D, and 3 W Post; Butenhoff and others (reference 93), Rats, S D (M), Gavage, P F O A, 28 D, and 3 W Post; Butenhoff and others (reference 93), Rats, S D (F), Gavage, P F O A, 28 D, E O T; Butenhoff and others (reference 93), Rats, S D (M), Gavage, P F O A, 28 D, E O T; Rigden and others (reference 92), Rats, S D (M), Gavage, P F O A, 3 D, and E O T; Martin and others (reference 99), Rats, S D (M), Gavage, P F O A, 5 D, and E O T; Martin and others (reference 99), Rats, S D (M), Gavage, P F O A, 2 D, and E O T; and Martin and others (reference 99), Rats, S D (M), Gavage, P F O A, 1 D, and E O T (y-axis) across Dose (milligrams per kilogram), ranging from 0 to 100 in increments of 50 and 300 (x-axis). The second strip plot, plotting reference, species, strain (sex), exposure route, exposure, duration, and sample collection, including (bottom to top) Son and others (reference 107), Mice, I C R (M), Water, P F O A, 21 D, and E O T; Botelho and others (reference 101), Mice, C 57 B L 6 (M), Diet, P F O A, 10 D, and E O T; Qazi and others (reference 105), Mice, C 57 B L 6 (M), Diet, P F O A plus Con A, 28 D, and E O T; Qazi and others (reference 105), Mice, C 57 B L 6 (M), Diet, P F O A, 28 D, and E O T; Qazi and others (reference 105), Mice, C 57 B L 6 (M), Diet, P F O A plus Con A, 10 D, and E O T; Qazi and others (reference 105), Mice, C 57 B L 6 (M), Diet, P F O A, 10 D, and E O T; Qazi and others (2010), Mice, C 57 B L 6 (M), Diet, P F O A, 10 D, and E O T; Butenhoff and others (reference 94), Rats, S D (F), Diet, P F O A, 2 Y, and E O T; Butenhoff and others (reference 94), Rats, S D (F), Diet, P F O A, 2 Y, and month 18; Butenhoff and others (reference 94), Rats, S D (F), Diet, P F O A, 2 Y, and month 12; Butenhoff and others (reference 94), Rats, S D (F), Diet, P F O A, 2 Y, and month 6; Butenhoff and others (reference 94), Rats, S D (F), Diet, P F O A, 2 Y, and month 3; Butenhoff and others (reference 94), Rats, S D (M), Diet, P F O A, 2 Y, and E O T; Butenhoff and others (reference 94), Rats, S D (M), Diet, P F O A, 2 Y, and month 18; Butenhoff and others (reference 94), Rats, S D (M), Diet, P F O A, 2 Y, and month 12; Butenhoff and others (reference 94), Rats, S D (M), Diet, P F O A, 2 Y, and month 6; and Butenhoff and others (reference 94), Rats, S D (M), Diet, P F O A, 2 Y, and month 3 (y-axis) across Dose (parts per million), ranging from 0 to 50 in increments of 50 and 250 to 300 in increments of 50 (x-axis).
Figure 2.
Strip plots for PFOA and ALT in animal studies. Triangles indicate a significant increase in ALT relative to control. Circles indicate no significant change in ALT relative to control. Additional exposures in Shi et al. refer to lactic acid bacterial strains. An accessible version of this figure is available in Table S5. Note: 4-PBA, 4-phenylbutyric acid; ALT, alanine aminotransferase; Con A, concanavalin A; D, day; E, embryonic day; EOT, end of treatment; F, female; GD, gestational day; GSPE, grape seed proanthocyanidin extract; HFD, high-fat diet; hPPAR, humanized peroxisome proliferator-activated receptor; LFD, low-fat diet; M, male; mPPAR, mouse peroxisome proliferator-activated receptor; NAC, N-acetylcysteine; PFOA, perfluorooctanoic acid; PND, postnatal day; Que, quecertin; SD, Sprague Dawley; W, week; Y, year.
Figure 3 is a set of two strip plots. The first strip plot, plotting reference, species, strain (sex), exposure route, exposure, duration, and sample collection, including (bottom to top) Marques and others (reference 130), Mice, C D -1 (M), Prenatal, P F O S plus H F D, G D 1 -P N D 21, and P N D 90; Marques and others (reference 130), Mice, C D -1 (M), Prenatal, P F O S, G D 1 -P N D 21, and P N D 90; Marques and others (reference 130), Mice, C D -1 (F), Prenatal, P F O S plus H F D, G D 1 -P N D 21, and P N D 90; Marques and others (reference 130), Mice, C D -1 (F), Prenatal, P F O S, G D 1 -P N D 21, and P N D 90; Marques and others (reference 130), Mice, C D -1 (M F), Prenatal, P F O S plus H F D, G D 1 -P N D 21, and P N D 90; Marques and others (reference 130), Mice, C D -1 (M F), Prenatal, P F O S, G D 1 -P N D 21, and P N D 90; Lai and others (reference 128), Mice, C 57 B L 7 (M F), Prenatal, P F O S plus D E N, E 0 to E 18.5, and E O T; Marques and others (reference 130), Mice, C D -1 (dams), Gavage, P F O S plus H F D, G D 1 -P N D 21, and E O T; Marques and others (reference 130), Mice, C D -1 (dams), Gavage, P F O S, G D 1 -P N D 21, and E O T; Hamilton and others (reference 125), Mice, Cyp2b -null (F), Gavage, P F O S plus H F D, 3 W, and E O T; Hamilton and others (reference 125), Mice, h C Y P 2 B 6 -T g (F), Gavage, P F O S plus H F D, 3 W, and E O T; Hamilton and others (reference 125), Mice, h C Y P 2 B 6 -T g (M), Gavage, P F O S plus H F D, 3 W, and E O T; Hamilton and others (reference 125), Mice, Cyp2b -null (F), Gavage, P F O S, 3 W, and E O T; Hamilton and others (reference 125), Mice, h C Y P 2 B 6 -T g (F), Gavage, P F O S, 3 W, and E O T; Hamilton and others (reference 125), Mice, Cyp2b -null (M), Gavage, P F O S, 3 W, and E O T; Hamilton and others (reference 125), Mice, h C Y P 2 B 6 -T g (M), Gavage, P F O S, 3 W, and E O T; Huang and others (reference 126), Mice, Kunming (M), Gavage, P F O S plus G S P E, 21 D, and E O T; Huang and others (reference 126), Mice, Kunming (M), Gavage, P F O S, 21 D, and E O T; Xing and others (reference 138), Mice, C 57 B L 7 (M), Gavage, P F O S, 30 D, and E O T; Wang and others (reference 137), Mice, C 57 B L 7 (M), Gavage, P F O S, 16 D, and E O T; Qin and others (reference 133), Mice, C 57 B L 7 (M), Gavage, P F O S plus H F D, 4 W, and E O T; Qin and others (reference 133), Mice, C 57 B L 7 (M), Gavage, P F O S, 4 W, and E O T; Deng and others (reference 124), Mice, C 57 B L 6 (M), Gavage, P F O S plus P C B 126, 1 D, and 2 D Post; Deng and others (reference 124), Mice, C 57 B L 6 (M), Gavage, P F O S, 1 D, and 2 D Post; Su and others (reference 135), Mice, I C R (M), Gavage, P F O S plus V C 200, 21 D, and E O T; Su and others (reference 135), Mice, I C R (M), Gavage, P F O S plus V C 100, 21 D, and E O T; Su and others (reference 135), Mice, I C R (M), Gavage, P F O S, 21 D, and E O T; Lv and others (reference 129), Mice, negative (M), Gavage, P F O S plus Nar, 21 D, and E O T; Lv and others (reference 129), Mice, negative (M), Gavage, P F O S, 21 D, and E O T; Yan and others (reference 89), Mice, B A L B c (M), Gavage, P F O S, 28 D, and EOT; Martin and others (reference 99), Rats, S D (M), Gavage, P F O S, and 5 D; Martin and others (reference 99), Rats, S D (M), Gavage, P F O S, and 2 D; Martin and others (reference 99), Rats, S D (M), Gavage, P F O S, and 1 D; Wan and others (reference 121), Rats, S D (M), Gavage, P F O S, 28 D, and EOT; Kim and others (reference 118), Rats, S D (F), Gavage, P F O S, 28 D, and EOT; Kim and others (reference 118), Rats, S D (M), Gavage, P F O S, 28 D, and EOT; Han and others (reference 117), Rats, S D (M), Gavage, P F O S, 28 D, and EOT; Han and others (reference 116), Rats, S D (M), Gavage, P F O S, 28 D, and EOT; Curran and others (reference 113), Rats, S D (F), Diet, P F O S, 28 D, and EOT; and Curran and others (reference 113), Rats, S D (M), Diet, P F O S, 28 D, and EOT (y-axis) across Dose (milligrams per kilogram), ranging from 0 to 100 in increments of 50 and 250 (x-axis). The second strip plot, plotting reference, species, strain (sex), exposure route, exposure, duration, and sample collection, including (bottom to top) Zhang and others (reference 140), Mice, C 57 B L 6 (M), Diet, P F O S plus C S, 6 W, and E O T; Zhang and others (reference 140), Mice, C 57 B L 6 (M), Diet, P F O S, 6 W, and E O T; Zhang and others (reference 140), Mice, C 57 B L 6 (M), Diet, P F O S plus m M C D, 2 W, and E O T; Zhang and others (reference 140), Mice, C 57 B L 6 (M), Diet, P F O S, 2 W, and E O T; Qazi and others (reference 132), Mice, C 57 B L 6 (M), Diet, P F O S plus Con A, 28 D, and E O T; Qazi and others (reference 132), Mice, C 57 B L 6 (M), Diet, P F O S, 28 D, and E O T; Qazi and others (reference 132), Mice, C 57 B L 6 (M), Diet, P F O S plus Con A, 10 D, and E O T; Qazi and others (reference 132), Mice, C 57 B L 6 (M), Diet, P F O S, 10 D, and E O T; Qazi and others (reference 104), Mice, C 57 B L 6 (M), Diet, P F O S, 10 D, and E O T; Butenhoff and others (reference 122), Rats, S D (F), Inhalation, P F O S, 13 W asterisk, and 4 W Post; Butenhoff and others (reference 122), Rats, S D (F), Inhalation, P F O S, 13 W asterisk, and E O T; Butenhoff and others (reference 122), Rats, S D (M), Inhalation, P F O S, 13 W asterisk, and 4 W Post; Butenhoff and others (reference 122), Rats, S D (M), Inhalation, P F O S, 13 W asterisk, and EOT; Bagley and others (reference 29), Rats, S D (F), Diet, P F O S plus C S, 23 D, and E O T; Bagley and others (reference 29), Rats, S D (F), Diet, P F O S, 23 D, and E O T; Bagley and others (reference 29), Rats, S D (F), Diet, P F O S plus C S, 16 D, and E O T; Bagley and others (reference 29), Rats, S D (F), Diet, P F O S, 16 D, and E O T; Bagley and others (reference 29), Rats, S D (F), Diet, P F O S plus C S, 9 D, and E O T; Bagley and others (reference 29), Rats, S D (F), Diet, P F O S, 9 D, and E O T; Bagley and others (reference 29), Rats, S D (F), Diet, P F O S plus C S, 2 D, and E O T; Bagley and others (reference 29), Rats, S D (F), Diet, P F O S, 2 D, and E O T; Bagley and others (reference 29), Rats, S D (M), Diet, P F O S plus C S, 23 D, and E O T; Bagley and others (reference 29), Rats, S D (M), Diet, P F O S, 23 D, and E O T; Bagley and others (reference 29), Rats, S D (M), Diet, P F O S plus C S, 16 D, and E O T; Bagley and others (reference 29), Rats, S D (M), Diet, P F O S, 16 D, and E O T; Bagley and others (reference 29), Rats, S D (M), Diet, P F O S plus C S, 9 D, and E O T; Bagley and others (reference 29), Rats, S D (M), Diet, P F O S, 9 D, and E O T; Bagley and others (reference 29), Rats, S D (M), Diet, P F O S plus C S, 2 D, and E O T; Bagley and others (reference 29), Rats, S D (M), Diet, P F O S, 2 D, and E O T; Butenhoff and others (reference 95), Rats, S D (M), Diet, P F O S, 52 W, and E O T; Butenhoff and others (reference 95), Rats, S D (M), Diet, P F O S, 52 W, and W 27; Butenhoff and others (reference 95), Rats, S D (M), Diet, P F O S, 52 W, and W 14; Butenhoff and others (reference 95), Rats, S D (M), Diet, P F O S, 52 W, and W 4; Butenhoff and others (reference 95), Rats, S D (F), Diet, P F O S, 52 W, and E O T; Butenhoff and others (reference 95), Rats, S D (F), Diet, P F O S, 52 W, and W 27; Butenhoff and others (reference 95), Rats, S D (F), Diet, P F O S, 52 W, and W 14; Butenhoff and others (reference 95), Rats, S D (F), Diet, P F O S, 52 W, and W 4; Elcombe and others (reference 114), Rats, S D (M), Diet, P F O S, 28 D, and E O T; Elcombe and others (reference 114), Rats, S D (M), Diet, P F O S, 7 D, and E O T; Elcombe and others (reference 114), Rats, S D (M), Diet, P F O S, 1 D, and E O T; Elcombe and others (reference 115), Rats, S D (M), Diet, P F O S, 7 D, and 84 D Post; Elcombe and others (reference 115), Rats, S D (M), Diet, P F O S, 7 D, and 56 D Post; Elcombe and others (reference 115), Rats, S D (M), Diet, P F O S, 7 D, 28 D, and EOT Post; Elcombe and others (reference 115), Rats, S D (M), Diet, P F O S, 7 D, and 1 D Post; Seacat and others (reference 120), Rats, S D (M), Diet, P F O S, 14 W, and E O T; and Seacat and others (reference 120), Rats, S D (F), Diet, P F O S, 14 W, and E O T (y-axis) across Dose (parts per million), ranging from 0 to 100 in increments of 50 and 300 (x-axis).
Figure 3.
Strip plots for PFOS and ALT in rodent studies. Triangles indicate a significant increase in ALT relative to control. Diamonds indicate a significant decrease in ALT relative to control. Circles indicate no significant change in ALT relative to control. Plots are ordered by species and strain. In the study by Butenhoff et al., atmospheric exposure occurred for 5 h/d, 5 d/wk. An accessible version of this figure is available in Table S6. Note: ALT, alanine aminotransferase; CS, choline supplementation; Con A, concanavalin A; D, day; DEN, diethylnitrosamine; EOT, end of treatment; F, female; GD, gestational day; GSPE, grape seed proanthocyanidin extract; HFD, high-fat diet; M, male; mMCD, marginal methionine/choline-deficient diet; Nar, naringin; PCB, polychlorinated biphenyl; PFOS, perfluorooctanesulfonic acid; PND, postnatal day; SD, Sprague Dawley; VC, vitamin C; W, week.
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Comment in

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