Public comments on IChEMS proposed standards

Original Investigation | Environmental Health

Effect of Plasma and Blood Donations on Levels of Perfluoroalkyl
and Polyfluoroalkyl Substances in Firefighters in Australia
A Randomized Clinical Trial
Robin Gasiorowski, PhD; Miriam K. Forbes, PhD; Gabriel Silver, MHealSc; Yordanka Krastev, PhD; Brenton Hamdorf, PhD; Barry Lewis, MBSy; Michael Tisbury;
Merrole Cole-Sinclair, MBBS; Bruce P. Lanphear, MD; Roger A. Klein, PhD; Nigel Holmes, BSc; Mark Patrick Taylor, PhD

Abstract Key Points
Question Can levels of perfluoroalkyl
IMPORTANCE Elevated levels of blood perfluoroalkyl and polyfluoroalkyl substances (PFASs) have
and polyfluoroalkyl substances (PFASs)
been associated with a range of adverse health outcomes. Firefighters have been exposed to PFASs
in the blood be reduced by blood or
in firefighting foams and have previously been shown to have higher PFAS levels in blood samples
plasma donations?
than the general population. No interventions have been shown to reduce PFAS levels.
Findings In this randomized clinical trial
OBJECTIVE To examine the effect of blood or plasma donations on PFAS levels in firefighters in of 285 firefighters, both blood and
Australia. plasma donations resulted in
significantly lower PFAS levels than
DESIGN, SETTING, AND PARTICIPANTS This 52-week, open-label, randomized clinical trial enrolled observation alone. Plasma donation was
participants from May 23 to August 23, 2019. Participants were 285 Fire Rescue Victoria staff or the most effective intervention,
contractors with serum levels of perfluorooctane sulfonate (PFOS) of 5 ng/mL or more who were reducing mean serum perfluorooctane
eligible to donate blood, had not donated blood in the 3 months prior to randomization, and were sulfonate levels by 2.9 ng/mL compared
able to provide written informed consent. Analysis was performed on an intention-to-treat basis with a 1.1-ng/mL reduction with blood
from May to July 2021. donation, a significant difference; similar
changes were seen with other PFASs.
INTERVENTIONS Firefighters with baseline PFOS levels of 5 ng/mL or more were randomly
Meaning Blood or plasma donations
assigned to donate plasma every 6 weeks for 12 months, donate blood every 12 weeks for 12 months,
may be used to reduce serum
or be observed only.
PFAS levels.

MAIN OUTCOMES AND MEASURES The primary end points were changes in the serum PFOS and
perfluorohexane sulfonic acid (PFHxS) levels after 12 months of plasma or blood donations or after + Visual Abstract
observation only. Secondary end points included changes in serum PFAS levels from week 52 to week
64, changes in other PFASs, and changes in complete blood count, biochemistry, thyroid function,
+ Supplemental content
Author affiliations and article information are
and lipid profile from screening to week 52.
listed at the end of this article.

RESULTS A total of 285 firefighters (279 men [97.9%]; mean [SD] age, 53.0 [8.4] years) were
enrolled; 95 were randomly assigned to donate plasma, 95 were randomly assigned to donate blood,
and 95 were randomly assigned to be observed. The mean level of PFOS at 12 months was
significantly reduced by plasma donation (–2.9 ng/mL; 95% CI, –3.6 to –2.3 ng/mL; P < .001) and
blood donation (–1.1 ng/mL; 95% CI, –1.5 to –0.7 ng/mL; P < .001) but was unchanged in the
observation group. The mean level of PFHxS was significantly reduced by plasma donation (–1.1
ng/mL; 95% CI, –1.6 to –0.7 ng/mL; P < .001), but no significant change was observed in the blood
donation or observation groups. Analysis between groups indicated that plasma donation had a
larger treatment effect than blood donation, but both were significantly more efficacious than
observation in reducing PFAS levels.

(continued)

Open Access. This is an open access article distributed under the terms of the CC-BY License.

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Abstract (continued)

CONCLUSIONS AND RELEVANCE Plasma and blood donations caused greater reductions in serum
PFAS levels than observation alone over a 12-month period. Further research is needed to evaluate
the clinical implications of these findings.

TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12619000204145

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Introduction
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic compounds used in a wide
variety of industrial and consumer products because of their resistance to heat and unique surfactant
properties. Uses include nonstick products, such as Teflon, stain- and water-resistant materials,
paints, and firefighting foams. Perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate
(PFOS), and perfluorooctanoic acid (PFOA) are commonly detected in human biomonitoring studies.
Perfluoroalkyl and polyfluoroalkyl substances persist in the environment and accumulate in the
human body, where they have a prolonged half-life (eg, 4.8 years for PFOS).1 The half-life of PFASs
in animals is shorter, limiting the utility of animal studies.2 The measurement of PFAS chemicals in
human populations coupled with their known persistence, bioaccumulation, and toxic effects—
particularly at higher levels among workers, such as firefighters,3 and in residential
communities4—has raised concerns about the detrimental effects of PFASs on health. Firefighters
have historically been exposed to firefighting foams that contain high levels of various PFASs;
previous studies have found that firefighters have higher PFAS levels in their blood, particularly of
PFOS and PFHxS, than the general population.5
Environmental and health agencies, including the European Chemicals Agency,6 the US Agency
for Toxic Substances and Disease Registry,7 the US Environmental Protection Agency,8 and the
Australian Government Department of Health,9 have identified that PFAS exposure has been
associated with adverse health effects. These effects include low fetal weight,10 impaired immune
response,11 thyroid function abnormalities,12 obesity,13 increased lipid levels,14,15 liver function
alterations,16 and, potentially, an increased risk of some malignant neoplasms.17 These associations
have been disputed by other authors,18 and the exact threshold at which these risks may increase
remains unknown. Nonetheless, several long carbon chain PFAS chemicals are considered potentially
carcinogenic19 as identified by the International Agency for Research on Cancer, who have classified
PFOA as a group 2B (possible) carcinogen for kidney and testicular cancers.20
Perfluoroalkyl and polyfluoroalkyl substances bind to serum proteins in the blood,21 so removal
of any blood containing these proteins may, over time, reduce the levels of PFASs in the blood.
Observational studies have found lower levels of PFASs in patients undergoing regular venesection.22
A small pilot study of 1 family suggested that regular venesection may reduce PFAS levels in the
blood.23 Premenopausal women have lower PFAS levels than men,24 perhaps from depuration of
PFASs with regular menstruation.25 Perfluoroalkyl and polyfluoroalkyl substances are measured in
serum or plasma,26 and, given that plasma can be safely removed more frequently than whole blood,
donating plasma may be a more effective way to reduce PFAS levels.
To our knowledge, the effect of plasma or blood donations on blood PFAS levels has not
previously been studied in a randomized clinical trial. We report the results of our randomized clinical
trial examining the effects of 12 months of regular plasma or blood donations on PFOS and PFHxS
levels in a cohort of Australian firefighters.

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Methods
Study Design and Participants
This is an open-label randomized clinical trial of selected Fire Rescue Victoria staff or contractors. We
prescreened participants via telephone and email before collecting written informed consent and
questionnaires and before obtaining blood samples at a single general practitioner practice. Blood
and plasma donations were collected at registered blood networks or at the same general
practitioner practice. This trial was approved by the Macquarie University Human Research Ethics
Committee. This report follows the Consolidated Standards of Reporting Trials (CONSORT) reporting
guideline for randomized studies.27
Study participants were current or former Fire Rescue Victoria staff or contractors with serum
PFOS levels of 5 ng/mL or more who were eligible to donate blood, had not donated blood in the 3
months prior to randomization, and were able and willing to provide written informed consent.
Participants with planned extended leave (eg, >6 weeks) were excluded. Full eligibility criteria are
provided in the previously published protocol.28
This study was conducted according to International Council for Harmonisation Guidelines for
Good Clinical Practice. The trial is registered with the Australian New Zealand Clinical Trials Registry
(ACTRN12619000204145; trial protocol in Supplement 1).

Randomization
We randomly assigned eligible participants to donate plasma every 6 weeks for 12 months, to donate
whole blood every 12 weeks for 12 months, or to be observed only. Covariate-adaptive
randomization29 was used to balance participants’ sex and baseline serum PFAS levels, stratified by
quartile, between the 3 groups. Randomization was computer generated and conducted centrally by
1 of the investigators (M.K.F.) who was not involved in the data collection or intervention.

Procedures
Participants had serum PFAS levels measured at screening, baseline (week 0), week 52, and week 64.
Participants randomly assigned to donate plasma gave plasma in amounts up to 800 mL every 6
weeks for a total of up to 9 plasma donations. Participants randomly assigned to donate whole blood
gave approximately 470 mL of blood every 12 weeks for a total of up to 5 donations. In both the
blood donation and plasma donation groups, the first donation was shortly after the baseline PFAS
blood test, and the final donation was scheduled for week 48, allowing 4 weeks between the final
donation and the week 52 PFAS blood test. No participants donated between the week 52 PFAS test
and the week 64 PFAS test to allow for the evaluation of any changes after donations ceased.
Full blood count, biochemistry, thyroid function, and lipid profile were also assessed at
screening and at week 52. Adverse events were reported to the clinical project manager and graded
by the principal investigator (R.G.) using the National Cancer Institute Common Terminology Criteria
for Adverse Events, version 4.03.30 All end point data were verified by an external data monitor prior
to analysis.

Outcomes
The coprimary end points were a change in serum PFOS and PFHxS levels after 12 months of plasma
or blood donations compared with baseline levels and with the observation group. Secondary end
points included changes in serum PFAS (PFOS or PFHxS) levels in each group from week 52 to week
64; changes in serum levels of 26 other PFAS chemicals (eAppendix in Supplement 2) from baseline
to week 52 and from week 52 to week 64; and changes in full blood count, biochemistry, thyroid
function, and lipid profile results from screening to week 52.

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Statistical Analysis
Analyses are based on intention to treat with G*Power, version 3.1.9.4,31 used for a priori power
analyses. As reported in the trial protocol, power analyses treated a 25% reduction in serum PFOS
and PFHxS levels as potentially clinically significant. Each group required 94 participants to have
90% power to detect this change within each group, corresponding to a small standardized mean
difference (Cohen d ⱖ 0.31), and 105 participants per group to have 90% power to detect a
conventional small effect size difference (partial η2 = 0.01) between the intervention groups with a
2-sided α of .05. The actual sample size of 95 participants per group achieves 87% power to detect
this effect size between groups and 90% power to detect partial η2 = 0.011. To further compare the
effect of plasma donation and whole blood donation to that of observation only, with a Bonferroni
correction for multiple testing to minimize type II error for the planned post hoc contrasts (2-sided
α = .017), the sample of 95 participants per group provides 75% power to detect the same small
effect size (partial η2 = 0.01 and 90% power to detect partial η2 = 0.014).
Primary analyses were planned a priori to examine the mean change within each group from
baseline to week 52 for blood serum levels of both PFOS and PFHxS as well as the mean differences
between treatment groups for both chemicals at week 52, controlling for their baseline levels. The a
priori statistical plan also included several secondary end points, including examining differences in
26 other PFAS chemicals, lipid profiles (total cholesterol, low-density lipoprotein cholesterol, high-
density lipoprotein cholesterol, and triglycerides), thyroid function (thyroid-stimulating hormone,
unbound T4, and T3), liver function, and kidney function at week 52, controlling for their results at
screening. Per-protocol analyses and descriptive analyses of treatment effects stratified by PFOS and
PFHxS quartiles were post hoc.
Full details of the statistical methods, including sensitivity analyses, are reported in the
eMethods in Supplement 2. Outliers more than 3 SDs from the mean were winsorized to 3 SDs, and
bootstrapping was used to account for the remaining nonnormality. The analyses were conducted in
a general linear model framework to facilitate robust sensitivity analyses.
We applied a studywide false discovery rate for all P values interpreted in the secondary end
point analyses (false discovery rate–corrected P < .20) to control for multiple comparisons and err on
the side of discovery, given that, to our knowledge, this is the first clinical trial to examine the efficacy
of blood and plasma donations in lowering serum PFAS levels and correlated physical health
indicators.32 Results are reported based on the adjusted P values, noting that the a priori analytical
plan specified that these analyses would focus on effect sizes over statistical significance. All analyses
were conducted in SPSS, version 27 (IBM Corp).

Results
Participant enrollment took place from May 23 to August 23, 2019. A total of 481 Fire Rescue Victoria
staff or contractors expressed interest in the study; 333 participants were screened and consented,
and 285 met the eligibility criterion of a serum PFOS level of 5 ng/mL or more (Figure 1). Most
participants (279 [97.9%]) were male, with a mean (SD) age of 53.0 (8.4) years (Table). Regression
toward the mean was evident for serum PFAS levels from screening to baseline, particularly for PFOS,
owing to the threshold applied for study eligibility. Participants in the intervention groups completed
a mean number of 6.4 (range, 0-9) plasma donations or 4.3 (range, 0-5) blood donations. The
participant retention rate was 93.7% (n = 267) for the duration of the study.

Serum PFOS Levels
From baseline to week 52 in the plasma donation group, mean PFOS levels were significantly reduced
(–2.9 ng/mL; 95% CI, –3.6 to –2.3 ng/mL; P < .001) (Figure 2A). For the blood donation group, mean
PFOS levels were also significantly reduced (–1.1 ng/mL; 95% CI, –1.5 to –0.7 ng/mL; P < .001). By
contrast, for the observation group, serum PFOS levels at week 52 were not significantly different
from baseline, with a mean decrease of 0.01 ng/mL (95% CI, −0.5 to 0.5 ng/mL; P = .96).

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Mean PFOS levels were reduced significantly more by both plasma donation (–3.1 ng/mL; 95%
CI, −3.8 to −2.4 ng/mL; P < .001) (Figure 2A) and blood donation (–1.1 ng/mL; 95% CI, −1.7 to −0.5
ng/mL; P < .001) compared with the observation group. Participants who donated plasma had mean
PFOS levels that were 2.0 ng/mL lower (95% CI, −2.6 to −1.3 ng/mL; P < .001) than PFOS levels
among those who donated blood.

Figure 1. Study Flow Diagram

481 Firefighters expressed interest
in participating

148 Excluded
84 Did not meet inclusion or
exclusion criteria
64 Declined to participate

333 Consented and were screened

48 Excluded for PFOS level <5 ng/mL

285 Randomized

95 Whole blood donation 95 Plasma donation 95 Observation

8 Excluded 4 Excluded
5 Excluded: withdrew
from study 6 Withdrew from study 2 Withdrew from study
2 Missed week 52 2 Missed week 52
blood test blood test

90 Analyzed for primary end point 87 Analyzed for primary end point 91 Analyzed for primary end point

PFOS indicates perfluorooctane sulfonate.

Table. Screening and Baseline Characteristics of the Intention-to-Treat Population
Observation Blood removal Plasma removal
Variable group (n = 95) group (n = 95) group (n = 95) Total (N = 285)
Age, mean (SD), y 54.3 (7.9) 51.3 (8.4) 53.3 (8.6) 53.0 (8.4)
[range, 32-77]
Sex, No. (%)
Female 2 (2.1) 2 (2.1) 2 (2.1) 6 (2.1)
Male 93 (97.9) 93 (97.9) 93 (97.9) 279 (97.()
Country of birth (Australia), No. (%) 84 (88.4) 87 (91.6) 90 (94.7) 261 (91.6)
Duration of exposure to AFFF, 23.3 (10.3) 20.4 (9.7) 22.0 (9.4) 21.9 (9.8)
mean (SD), y [range, 2-46]
History of blood donation, No. (%) 67 (70.5) 57 (60.0) 64 (67.4) 188 (66.0)
BMI, mean (SD) 28.0 (3.4) 27.9 (4.0) 27.9 (3.4) 27.9 (3.6)
[range, 19.9-44.6]
PFOS levelsa
Abbreviations: AFFF, aqueous film forming foam; BMI,
Screening, mean (SD), ng/mL 12.5 (6.8) 12.4 (9.5) 14.2 (17.9) 13.0 (12.3)
[range, 5-170] body mass index (calculated as weight in kilograms
Baseline, mean (SD), ng/mL 10.7 (5.9) 10.9 (8.3) 11.7 (20.1) 11.1 (12.9) divided by height in meters squared); PFHxS,
[range, 2-190] perfluorohexane sulfonic acid; PFOS, perfluorooctane
PFHxS levelsa sulfonate.
a
Screening, mean (SD), ng/mL 4.5 (6.0) 4.3 (6.1) 5.9 (12.9) 4.9 (8.9) PFOS and PFHxS values include outliers in the
[range, 0-120] observed raw values reported here; outliers more
Baseline, mean (SD), ng/mL 3.9 (5.7) 3.6 (5.0) 5.2 (15.0) 4.2 (9.7) than 3 SDs from the mean were winsorized to 3 SDs
[range, 0-140]
for all other analyses.

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Serum PFHxS Levels
In the plasma donation group, mean PFHxS levels were significantly reduced (–1.1 ng/mL; 95% CI, –1.6
to –0.7 ng/mL; P < .001) (Figure 2B). In both the observation and blood donation groups, mean
PFHxS levels were not significantly different from baseline, increasing 0.4 ng/mL (95% CI, −0.01 to
0.7 ng/mL; P = .06) in the observation group and decreasing 0.1 ng/mL (95% CI, −0.4 to 0.2 ng/mL;
P = .54) in the blood donation group.
Compared with the observation group, mean PFHxS levels were reduced significantly more by
both plasma donation (–1.5 ng/mL; 95% CI, −1.9 to −1.1 ng/mL; P < .001) and blood donation (–0.6
ng/mL; 95% CI, −0.9 to −0.2 ng/mL; P = .001). Participants who donated plasma had mean PFHxS
levels that were 0.9 ng/mL (95% CI, −1.3 to −0.6 ng/mL; P < .001) lower than mean PFHxS levels in
those who donated blood. Key results from sensitivity analyses for the primary end points are
reported in the eMethods in Supplement 2.

Secondary PFAS End Point Levels
Secondary end points included 26 additional PFASs, but only PFOA had sufficient data for analysis;
nearly all (range, 93.0% [265] to 100%) participants had undetectable levels of the other 25 PFASs at
baseline. In the plasma donation group, mean PFOA levels were significantly reduced (–0.5 ng/mL;
95% CI, –0.7 to –0.3 ng/mL; P = .001) (Figure 3C). In the blood donation group, mean PFOA levels
were not significantly different from baseline at week 52, with a reduction of 0.1 ng/mL (95% CI, −0.2
to 0.1 ng/mL; P = .63). In the observation group, mean PFOA levels at week 52 had a small but
statistically significant increase of 0.2 ng/mL from baseline (95% CI, 0.1-0.3 ng/mL; P = .02).
Compared with the observation group, mean serum PFOA levels were reduced significantly
more in both the plasma donation group (–0.8 ng/mL; 95% CI, −0.9 to −0.6 ng/mL; P = .001) and the
blood donation group (–0.3 ng/mL; 95% CI, −0.4 to −0.1 ng/mL; P = .007) from baseline to week 52.
Participants who donated plasma had mean PFOA levels that were 0.5 ng/mL (95% CI, −0.7 to −0.3
ng/mL; P = .001) lower than PFOA levels among those who donated blood.
Mean (SD) PFOA levels were low at baseline (1.2 [1.1] ng/mL) and close to the detection limit of 1
ng/mL across the entire cohort; sensitivity analyses recoding all serum PFOA levels below the limits
of reporting at the upper bound of the threshold (<1 ng/mL recoded to 1 ng/mL) showed a smaller
mean reduction due to plasma donation from baseline to week 52 (–0.2 ng/mL; 95% CI, –0.4 to –0.1
ng/mL; P = .003) and an insignificant increase in the observation group (0.1 ng/mL; 95% CI, 0.0-0.2

Figure 2. Mean Change in Perfluoroalkyl and Polyfluoroalkyl Substances From Baseline to Week 52

A Mean change in PFOS level B Mean change in PFHxS level
All P <.001
All P <.001
12 5
P =.96

10 P <.001 P =.06
4
P =.54
P <.001
PFHxS level, ng/mL
PFOS level, ng/mL

8
3 P =.001

6

2
4 Observation only
Blood donation
Plasma donation 1
2

0 0
0 4 8 12 16 20 24 28 32 36 40 44 48 52 0 4 8 12 16 20 24 28 32 36 40 44 48 52

No. of weeks No. of weeks

A, Mean change in perfluorooctane sulfonate (PFOS) level from baseline to week 52. B, either outcome (P = .96 for PFOS and P = .06 for PFHxS); change in the blood donation
Mean change in perfluorohexane sulfonic acid (PFHxS) level from baseline to week 52. group was significant for PFOS (P < .001) but not for PFHxS (P = .54); and change in the
Error bars indicate the SEM. Change in the observation group was not significant for plasma donation group was significant for both outcomes (all P < .001).

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ng/mL; P = .22). The differences between groups were correspondingly smaller but remained
statistically significant even after applying the false discovery rate.

Other Secondary End Points
Treatment differences between study groups were maintained from week 52 to week 64 for PFOS,
PFHxS, and PFOA levels (Figure 3). Across the entire study cohort, however, a slight increase was
observed in serum PFOS levels (0.2 ng/mL; 95% CI, 0.1-0.3 ng/mL; P = .001) and serum PFOA levels

Figure 3. Observed Mean Change in Perfluoroalkyl and Polyfluoroalkyl Substances, Including
the Follow-up Period

A Mean change in PFOS level

12

10
PFOS level, ng/mL

8

6

4 Observation only
Blood donation
2 Plasma donation

0
0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64

No. of weeks

B Mean change in PFHxS level
5

4
PFHxS level, ng/mL

3

2

1

0
0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64

No. of weeks

C Mean change in PFOA level
2.0

1.5
PFOA level, ng/mL

1.0

0.5 A, Mean change in perfluorooctane sulfonate (PFOS)
level, including the follow-up period. B, Mean change
in perfluorohexane sulfonic acid (PFHxS) level,
0 including the follow-up period. C, Mean change in
0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64
perfluorooctanoic acid (PFOA) level, including the
No. of weeks follow-up period. Error bars indicate the SEM.

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(0.1 ng/mL; 95% CI, 0.1-0.2 ng/mL; P = .006), with a slight decrease in PFHxS levels (−0.1 ng/mL;
95% CI, −0.2 to −0.1 ng/mL; P = .004).
Hemoglobin levels were reduced more in the blood donation group than in the plasma donation
group (−0.51 g/dL; 95% CI, −0.72 to 0.29 g/dL [to convert to grams per liter, multipy by 10.0];
P = .001) or the observation group (−0.45 g/dL; 95% CI, −0.64 to −0.25 g/dL; P = .001), but
otherwise no significant differences were observed for lipid profile, thyroid, liver, or kidney function
test results between groups at week 52 after controlling for baseline levels (eResults and eFigures
1-3 in Supplement 2).
Adverse events were more frequent in the plasma donation group (eTable in Supplement 2). A
total of 13 (4.6%) participants withdrew from the study, and 268 (94.0%) had complete data for
baseline and week 52 PFAS levels; their results are included in the intention-to-treat analysis
regardless of how many donations were completed. This intention-to-treat analysis provides a more
conservative view of the effect of the interventions because not every participant was able to
complete the study as planned. Per-protocol analyses of the subsample of participants with data at
week 52 who completed all blood donations (n = 68) or all plasma donations (n = 47) showed similar
results with slightly larger effect sizes (eFigure 4 in Supplement 2).
A post hoc descriptive analysis of treatment effects stratified by PFOS and PFHxS quartiles at
baseline indicated a potential pattern of larger treatment effects for participants with serum levels in
the top quartile, particularly for plasma donation. This difference was not apparent in the observation
group (Figure 4).

Discussion
To our knowledge, this is the first randomized clinical trial to systematically quantify whether plasma
or blood removal is an effective strategy for reducing serum PFAS levels. Plasma donations resulted
in a more substantial decrease in serum PFAS levels than blood donations, and both treatments were
more effective than observation alone. This difference may arise because participants in the plasma
group were able to donate every 6 weeks rather than every 12 weeks for whole blood. Each plasma
donation can amount to as much as 800 mL compared with 470 mL for whole blood; the increased
volume may contribute to the faster reduction in serum PFAS levels found in the plasma donation
group. In addition, plasma donation may be more efficient at reducing the body’s burden of PFASs
because serum PFAS levels are approximately 2 times higher than blood PFAS levels.26 On the other
hand, plasma donation is more complex, and adherence to the protocol was lower for this group;
the mean number of plasma donations was 6.4 of the 9 planned compared with 4.3 of the 5 planned
whole blood donations during the study period. Future research should investigate the role of the
number, frequency, and volume of each donation to elucidate these likely mechanisms of
treatment change.
Mean serum PFOS, PFHxS, and PFOA levels at baseline were lower in this study than the mean
levels observed in another cohort of Australian firefighters.5 This difference may reflect a natural
decrease in PFAS levels over time, as has been described in American Red Cross blood donors,33
along with efforts to reduce PFAS exposure among firefighters. The mean PFAS levels found in our
study population were similar to those reported for the general Australian population.5
Blood donors who have elevated serum PFAS levels are not excluded from donating blood.
Perfluoroalkyl and polyfluoroalkyl substances are ubiquitous, and no threshold has been identified
that poses an increased risk to recipients of donated blood components. Our study does not inform
this risk, but blood authorities should continue to monitor the evidence on the possible health effects
of PFASs and consider the possible implications of elevated PFAS levels in blood donors.
We did not find a decrease in serum PFAS levels among participants assigned to the observation
group. We observed a small but statistically significant increase in PFOA levels over the 52 weeks
among participants assigned to the observation group, but serum PFOS and PFHxS levels were
unchanged. The half-lives for PFOS, PFHxS, and PFOA have previously been reported as 4.8, 7.3, and

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JAMA Network Open | Environmental Health Effect of Plasma and Blood Donations on PFAS Levels in Firefighters in Australia

3.5 years, respectively,1 so during a 12-month period, we would have expected PFAS levels to
decrease by approximately 10%. In our cohort, the baseline levels were substantially lower than
those in the previous study,5 which may explain the lower-than-expected changes in PFAS levels in
the control group. In addition, the observed changes may be due to ongoing environmental exposure
or redistribution between body compartments (eg, moving from liver to plasma), but the limit of
detection for the PFAS assays was 1 ng/mL, so any changes close to this threshold need to be
interpreted with caution.

Limitations
This study has some limitations. Serum PFAS levels were measured at screening, baseline, week 52,
and week 64 but were not assessed during the intervention (ie, between baseline and week 52), so
we are not able to comment further on the kinetics of PFAS clearance. However, the treatment
effects were maintained during the 12-week follow-up period from week 52 to week 64. Although
these study data provide evidence for sustained efficacy of plasma and blood donations to reduce
serum PFAS levels, extended follow-up of the cohort would be useful to assess changes in PFAS
serum levels over time.
Although elevated PFAS levels have previously been shown to be associated with
hyperlipidemia,15 elevated liver function test results,16 and thyroxine levels,12 we did not see any

Figure 4. Treatment Effects Stratified by Quartiles at Baseline

A Mean (SE) change in PFOS level, ng/mL Decreasing Increasing
PFOS level PFOS level
Q1 observation = 0.0 (0.26)
Q2 observation = –0.5 (0.55)
Q3 observation = 0.2 (0.45)
Q4 observation = 0.2 (0.75)
Total observation = 0.0 (0.25)
Q1 blood donation = –1 (0.22)
Q2 blood donation = –1.1 (0.31)
Q3 blood donation = –0.9 (0.48)
Q4 blood donation = –1.7 (0.71)
Total blood donation = –1.1 (0.21)
Q1 plasma = –1.7 (0.3)
Q2 plasma = –2.9 (0.48)
Q3 plasma = –2.7 (0.67)
Q4 plasma = –5.7 (1.03)
Total plasma = –2.9 (0.33)

–8 –7 –6 –5 –4 –3 –2 –1 0 1 2
PFOS change, ng/mL

B Mean (SE) change in PFHxS level, ng/mL Decreasing Increasing
PFHxS level PFHxS level
Q1 observation = 0.4 (0.09)
Q2 observation = 0.3 (0.34)
Q3 observation = 0.5 (0.22)
Q4 observation = 0.3 (0.74)
Total observation = 0.4 (0.18)
Q1 blood donation = 0.2 (0.12)
Q2 blood donation = –0.3 (0.26)
Q3 blood donation = 0.0 (0.11)
Q4 blood donation = –0.7 (0.7)
Total blood donation = –0.1 (0.15)
Q1 plasma = –0.5 (0.14)
Q2 plasma = –0.4 (0.26)
Q3 plasma = –0.9 (0.25)
Q4 plasma = –2.9 (0.76)
A, Mean (SE) change in perfluorooctane sulfonate
Total plasma = –1.1 (0.23)
(PFOS) level from baseline to week 52. B, Mean (SE)
–4 –3 –2 –1 0 1 2 change in perfluorohexane sulfonic acid (PFHxS) level
PFHxS change, ng/mL from baseline to week 52. Q indicates quartile.

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JAMA Network Open | Environmental Health Effect of Plasma and Blood Donations on PFAS Levels in Firefighters in Australia

significant change in lipid levels or other clinical blood test results, with the exception of lower
hemoglobin levels from blood donations, as a result of these interventions. This outcome is perhaps
not surprising in a relatively small heterogenous cohort. Larger studies examining these clinical end
points should be performed.
As for PFOA levels in the observation group, minor changes were noted in PFAS levels during
this follow-up period; PFOS and PFOA levels increased slightly, whereas PFHxS levels decreased
slightly. It is not clear whether these postintervention changes reflect ongoing exposures, shifts from
body tissue stores of PFAS into plasma, or variation in the PFAS assay. Further follow-up of this study
cohort would be helpful to address this question as well as to explore the potential mechanisms for
treatment effects from baseline to week 52.
In 2016, the Human Biomonitoring Commission of the German Environment Agency
determined human biomonitoring (HBM)–I plasma levels of 5 ng/mL for PFOS and 2 ng/mL for PFOA,
below which no adverse health effects are expected.34 More recently, the Human Biomonitoring
Commission derived HBM-II plasma thresholds for the general population, excluding women of
childbearing age, of 20 ng/mL for PFOS and 10 ng/mL for PFOA, which, when exceeded, may lead to
health impairments.35,36 Given the long half-life of PFASs both for bioelimination and environmental
persistence, ongoing exposures will persist for decades. Regulations to reduce widespread PFAS
exposure are needed, but an intervention that can reduce PFAS levels in exposed populations would
be a useful adjunct.

Conclusions
This randomized clinical trial showed that regular blood or plasma donations result in a significant
reduction in serum PFAS levels for participants with a baseline PFOS level of 5 ng/mL or more; plasma
donations reduced levels more quickly than blood donations. Blood and plasma removal are
relatively straightforward procedures, and, provided they are performed under medical supervision,
the risks to the patient are minimal. Further research is warranted to investigate the clinical effects
of reducing PFAS levels and to better define the cohorts who would benefit most from these
interventions.

ARTICLE INFORMATION
Accepted for Publication: February 19, 2022.
Published: April 8, 2022. doi:10.1001/jamanetworkopen.2022.6257
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022
Gasiorowski R et al. JAMA Network Open.
Corresponding Author: Robin Gasiorowski, PhD, Faculty of Medicine, Health and Human Sciences, Macquarie
University, Balaclava Road, Macquarie Park, NSW 2109, Australia (robin.gasiorowski@mq.edu.au).
Author Affiliations: Faculty of Medicine, Health and Human Sciences, Macquarie University, New South Wales,
Australia (Gasiorowski, Forbes, Silver, Krastev, Hamdorf); Department of Haematology, Concord Repatriation
General Hospital, New South Wales, Australia (Gasiorowski); Centre for Emotional Health and School of
Psychological Sciences, Macquarie University, New South Wales, Australia (Forbes); Now with Research,
Innovation & Enterprise, Office of the Deputy Vice Chancellor, Research, Macquarie University, New South Wales,
Australia (Hamdorf); High Consequence Chemical Response Capability Project, Fire Rescue Victoria (FRV),
Victoria, Australia (Lewis); FRV Advocacy, FRV, Victoria, Australia (Tisbury); Laboratory Haematology Department,
St Vincent’s Hospital, Melbourne, Victoria, Australia (Cole-Sinclair); Faculty of Health Sciences, Simon Fraser
University, Vancouver, British Columbia, Canada (Lanphear); Retired, Cambridge, United Kingdom (Klein);
Christian Regenhard Center for Emergency Response Studies, City University of New York, New York (Klein);
Incident Response Unit, Environmental Services and Regulation, Queensland Department of Environment and
Science, Queensland, Australia (Holmes); Environment Protection Authority Victoria, EPA Science, Centre for
Applied Sciences, Macleod, Melbourne, Victoria, Australia (Taylor); Earth and Environmental Sciences, Faculty of
Science & Engineering, Macquarie University, New South Wales, Australia (Taylor).

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Author Contributions: Dr Forbes had full access to all of the data in the study and takes responsibility for the
integrity of the data and the accuracy of the data analysis.
Concept and design: Gasiorowski, Forbes, Silver, Krastev, Hamdorf, Lewis, Tisbury, Cole-Sinclair, Klein, Taylor.
Acquisition, analysis, or interpretation of data: Gasiorowski, Forbes, Silver, Lewis, Tisbury, Cole-Sinclair, Lanphear,
Holmes, Taylor.
Drafting of the manuscript: Gasiorowski, Forbes, Silver, Lewis, Tisbury, Taylor.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Forbes.
Obtained funding: Krastev, Hamdorf, Lewis, Tisbury, Taylor.
Administrative, technical, or material support: Silver, Krastev, Hamdorf, Lewis, Tisbury, Cole-Sinclair,
Holmes, Taylor.
Supervision: Gasiorowski, Krastev, Lewis, Tisbury, Lanphear.
Conflict of Interest Disclosures: Drs Gasiorowski, Forbes, Krastev, Hamdorf, and Taylor and Mr Tisbury reported
receiving grants from Fire Rescue Victoria (formerly Victorian Metropolitan Fire Brigade) during the conduct of the
study. Mr Tisbury reported being an employee of Fire Rescue Victoria and previously being the Vice President of
the United Firefighters Union, Victorian Branch. Dr Taylor reported that part of his work involves working with
emergency services, including Fire Rescue Victoria. No other disclosures were reported.
Funding/Support: This study was funded by Fire Rescue Victoria, Australia.
Role of the Funder/Sponsor: Two Fire Rescue Victoria staff were involved in the design and implementation of
this clinical trial. The final protocol, oversight of the trial, and analysis and reporting of the data were the
responsibility of the Macquarie University research team.
Data Sharing Statement: See Supplement 3.
Additional Contributions: St Vincent’s General Practice Clinics, Melbourne, Victoria, Australia, performed
screening and consenting of participants and some phlebotomy services. Envirolab Services Pty Ltd, Sydney, New
South Wales, Australia, performed the perfluoroalkyl and polyfluoroalkyl substance testing. Jenison Violet
Consulting Pty Ltd, Avalon, New South Wales, Australia, performed data monitoring. Power Stats, West Ryde, New
South Wales, Australia, provided statistical peer review.

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31. Heinrich Heine Universität Düsseldorf. G*Power. Accessed February 28, 2022. https://www.psychologie.hhu.
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36. Schümann M, Lilienthal H, Hölzer J. Human biomonitoring (HBM)-II values for perfluorooctanoic acid (PFOA)
and perfluorooctane sulfonic acid (PFOS)—Description, derivation and discussion. Regul Toxicol Pharmacol.
2021;121:104868. doi:10.1016/j.yrtph.2021.104868

SUPPLEMENT 1.
Trial Protocol

SUPPLEMENT 2.
eMethods.
eResults.
eFigure 1. Association Between Screening and Week 52 Levels of TSH
eFigure 2. Association Between Screening and Week 52 Levels of ALT
eFigure 3. Association Between Screening and Week 52 Levels of Platelets
eTable. Adverse Events
eFigure 4. Per-Protocol Analysis
eAppendix.

SUPPLEMENT 3.
Data Sharing Statement

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Organisational Policy

Per- and Polyfluoroalkyl Substances (PFAS)

1. Purpose
The purpose of this policy is to ensure the continued advocacy works across the
whole of FRV in the removal and mitigation of PFAS contamination being
conducted by the FRV PFAS Project Team.

These works include the following:
▪ Removal of fluorinated foams
▪ Decontamination of FRV Appliances
▪ FRV PFAS Blood Reduction Study
▪ PFAS Remediation works at FRV sites and surrounding properties
▪ Trial of self-contained garden beds
▪ Any other PFAS related matter.
The use of best practice and industry innovation in conducting environmental
remediation and mitigation works. The FRV PFAS Project Team will continue to
work with both internal and external stakeholders and/or agencies to ensure best
practice for all FRV employees is adhered to when conducting PFAS remediation
works.

2. Scope and Application
This policy applies to all FRV Operational and Corporate Personnel.

This policy is to be read in conjunction with the relevant doctrine within the FRV
Doctrine Framework.

3. Definitions
Definitions for commonly used terms can be found in the FRV Doctrine Glossary
of Terms. The following definitions are specific to this policy only:

▪ AFFF – Aqueous Film Forming Foam
▪ PFAS – Per- and polyfluoroalkyl substances (PFAS) are a diverse group
of compounds resistant to heat, water, and oil. Perfluorohexane
sulfonate (PFHxS), perfluoroctane sulfonate (PFOS) and
perfluorooctanoic acid (PFOA) are the most prominent and commonly
detected PFAS. For many years, they have been used in hundreds of
industrial applications and consumer products such as carpeting,
apparel, upholstery, food paper wrappings, firefighting foams and metal
coatings.
▪ Precautionary principle - The concept that establishes it is better to
avoid or mitigate an action or policy that has the plausible potential,
based on scientific analysis, to result in major or irreversible negative
consequences to the environment or public even if the consequences of
that activity are not conclusively known, with the burden of proof that it
is not harmful falling on those proposing the action. It is a major principle
Page 2 of 5

of international environmental law and is extended to other areas and
jurisdictions as well.

4. Responsibilities
Overarching responsibilities are defined in the FRV Doctrine Framework Policy.
The specific responsibilities for various personnel are defined below:

4.1 Fire Rescue Commissioner
The Fire Rescue Commissioner will support Fire Rescue Victoria employees, the
Victorian Government, Emergency Management Victoria (EMV) and other
emergency services/agencies to ensure the ongoing support for PFAS
Remediation works.
4.2 Executive Leadership Team
The Executive Leadership Team will continue to support a precautionary principle
regarding PFAS Remediation works identified by the FRV PFAS Project Team.
4.3 Executive Managers/ACFOs
The FRV Executive Managers/ACFOs will continue to support a precautionary
principle regarding PFAS Remediation works identified by the FRV PFAS Project
Team.
4.4 Line Managers/Commanders
Line Managers/Commanders are responsible for enforcing all current policy and
procedures regarding the PFAS remediation works, while reporting any potential
exposures in the workplace which may be identified while performing their duties
in both operational and functional roles within FRV.
4.5 Corporate Personnel
Employees and contractors are responsible for carrying out their duties in a manner
which minimises and improves our compliance with the current PFAS mitigation
policies and strategies.
4.6 Operational Personnel
All FRV Operational Personnel are required to be aware of the PFAS Policy while
responding and protecting the community, including the following:
▪ Potential cross contamination from non FRV appliances
▪ Possible contamination using fluorinated foams from major hazardous
facilities (MHF)
▪ No storage of fluorinated foams on any FRV sites
▪ No storage of ‘A’ Class foam on any FRV fire stations or workplaces. If
identified on such sites, CFA is to be contacted for ownership and
removal.
Note: Exception to this applies for the amount of foam stored on the
CFA appliance.
Operational Personnel are to work in conjunction with the PFAS Project Team
during any Fire Station remediation works.

Per- and Polyfluoroalkyl Substances (PFAS) – 14 Oct 2022 – V1.0
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Page 3 of 5

4.7 PFAS Project Team
The PFAS Project Team remediate and remove PFAS from FRV work sites,
appliances, and equipment to ensure the continued application of the
precautionary principle regarding PFAS across the whole of organisation. The
PFAS Project Team also work with the community to reduce any PFAS exposure
and contamination by FRV.
The PFAS Project Team will coordinate and advise any PFAS remediation work to
any FRV Fire Station/Workplace including appliances and equipment. The PFAS
remediation works will be conducted in partnership with our identified industry
experts to ensure that best practice is achieved while conducting these works.
Such works include:
▪ Testing of soil
▪ Appliances
▪ Equipment
▪ PPC
▪ Adjoining properties
▪ Fire stations
▪ Storm water systems
▪ Ground water systems
▪ Environmental receptors
▪ Human Health Risk Assessments.
Remediation is to be completed as required when identified by the PFAS
Project Team.
For further information, the PFAS Project Team can be contacted via email at
PFAS@frv.vic.giv.au or the intranet page PFAS Remediation Program

5. Policy Principles
5.1 Use of firefighting foam
▪ Only utilise non-fluorinated foams approved for use by FRV.
5.2 FRV Appliance PFAS Decontamination Process
▪ All FRV appliances have completed the PFAS decontamination process.
Appliances have been labelled with a blue or green sticker following
the decontamination process which indicates the level of residual
PFAS as per the following table:
Endorsed FRV Appliance PFAS Residual Sum of PFHxS and PFOS
Threshold Limits
Derived Human Health Threshold Levels 413 ug/l (Parts per Billion)
FIREFIGHTING
OPERATIONS LEVEL
(Green Sticker)
VEMTC Craigieburn Level FIREFIGHTING 70 ppt
TRAINING LEVEL (Parts Per Trillion)
(Blue Sticker) 0.07 ug/l

Per- and Polyfluoroalkyl Substances (PFAS) – 14 Oct 2022 – V1.0
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Page 4 of 5

5.3 Relay pumping from appliances
▪ Relay pumping may be conducted from any FRV appliance.
▪ Relay pumping may be conducted from any Aviation Rescue Firefighting
(ARFF) appliance.
▪ Water supplies suspected to be PFAS contaminated should not be used
unless there is an imminent threat to life or rapid escalation of fire growth.
▪ Where an OIC is unable to confirm the status of the water used during an
incident, all appliances must be flushed on the completion of operations.
▪ In circumstances where cross contamination may have occurred, upon
return to station:
o Notify PFAS Project Team via email PFAS@frv.vic.gov.au
o Flush the appliance fully and thoroughly in accordance with
the PFAS Remediation requirements
Note: The PFAS Project team will determine if it is necessary for further
testing and decontamination.
5.4 Major Hazard Facilities (MHFs) and other locations with on-site foam
▪ On-site foam is not to be used unless one of the following applies:
o an immediate threat to life
o risk of rapid fire growth
o current certification of fluorine free foam.
▪ Static water at Major Hazard Facilities (MHFs) may be used on the
assumption that the static water does not contain PFAS levels above
the accepted thresholds.
5.5 Strike Teams
▪ Static water may be used on the assumption that the static water does
not contain PFAS levels above the accepted thresholds.
5.6 Training
▪ Static water supplies should not be used for open water training unless
the training is conducted at VEMTC or with the use of FRV Recycled
Water PODS or mains water. Any other agreed training or training
facility will need to be endorsed through the Consultation Committee in
accordance with the Enterprise Agreement.
5.7 Water and soil sampling
▪ Water and soil sampling will be conducted when deemed required by the
PFAS Project Team.
▪ Water and soil sampling is only to be conducted by qualified FRV
personnel who have successfully completed the industry recognised
standard training course.

6. Authorising Documents
Authorising documents related to FRV can be found on the FRV Doctrine intranet
site.

▪ Nil

Per- and Polyfluoroalkyl Substances (PFAS) – 14 Oct 2022 – V1.0
This document is uncontrolled when printed. Refer to the FRV Doctrine intranet page for the most current version.
Page 5 of 5

7. Supporting Documents/Links
7.1 Report
▪ FRV Appliance PFAS Cross Contamination Assessment

8. Document Information
8.1 Document Control

Doctrine Number POL 020
Doc ID 0017-382875174-109
Approval Authority Operational Consultation Committee
Issue Date 14 Oct 2022
Effective Date 14 Oct 2022
Review Frequency Biennially
Custodian ACFO – Fire Safety Advocacy

8.2 Version Control

Date Date Next Review Nature of
Version
Amended Approved Date Amendment
12 Oct 2022 14 Oct 2024 Document
1.0
published

Per- and Polyfluoroalkyl Substances (PFAS) – 14 Oct 2022 – V1.0
This document is uncontrolled when printed. Refer to the FRV Doctrine intranet page for the most current version.