Half-lives of PFOS, PFHxS and PFOA after end of exposure to contaminated drinking water
Ying Li Tony Fletcher Daniel Mucs Kristin Scott Christian H Lindh Pia Tallving Kristina Jakobsson
Background Municipal drinking water contaminated with perfluorinated alkyl acids had been distributed to one-third of households in Ronneby, Sweden. The source was firefighting foam used in a nearby airfield since the mid-1980s. Clean water was provided from 16 December 2013.

Objective To determine the rates of decline in serum perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), and their corresponding half-lives.

Methods Up to seven blood samples were collected between June 2014 and September 2016 from 106 participants (age 4–84 years, 53% female).

Results Median initial serum concentrations were PFHxS, 277 ng/mL (range 12–1660); PFOS, 345 ng/mL (range 24–1500); and PFOA, 18 ng/mL (range 2.4–92). The covariate-adjusted average rates of decrease in serum were PFHxS, 13% per year (95% CI 12% to 15%); PFOS, 20% per year (95% CI 19% to 22%); and PFOA, 26% per year (95% CI 24% to 28%). The observed data are consistent with a first-order elimination model. The mean estimated half-life was 5.3 years (95% CI 4.6 to 6.0) for PFHxS, 3.4 years (95% CI 3.1 to 3.7) for PFOS and 2.7 years (95% CI 2.5 to 2.9) for PFOA. The interindividual variation of half-life was around threefold when comparing the 5th and 95th percentiles. There was a marked sex difference with more rapid elimination in women for PFHxS and PFOS, but only marginally for PFOA.

Conclusions The estimated half-life for PFHxS was considerably longer than for PFOS and PFOA. For PFHxS and PFOS, the average half-life is shorter than the previously published estimates. For PFOA the half-life is in line with the range of published estimates.
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Occupational & Environmental Medicine
Introduction

Perfluorinated and polyfluorinated substances (PFASs) comprise a group of many different synthetic substances that have been produced and widely used for approximately 50 years. They are found in industrial applications and household products mainly due to their properties of withstanding heat, oil, dirt and water. PFASs are also used as surfactants in firefighting foam of the aqueous film forming foam (AFFF) type.1

In the general population, the dominating sources of exposure are through diet and consumer products.2 However, during the past decade it has become apparent that localised PFAS contamination to surface and groundwater occurs around military and civilian firefighting training facilities, where large quantities of AFFF foams have been used. These substances are further disseminated by means of groundwater flows, and may also reach drinking water wells.

PFASs are excreted via urine and faeces. In animals half-lives (T½) for PFASs vary markedly between species and are usually much shorter than in humans, with elimination half-life counted in hours or days.3 Reabsorption by organic anion transporters (OATs) in the kidneys and extensive uptake from enterohepatic circulation for PFASs are believed to be more active processes in humans, slowing down the excretion of these substances. In observational studies, based on observations in individuals followed over time, T½ between 2 and 3 years was reported for perfluorooctanoic acid (PFOA), while longer half-lives for perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), 4 and 7 years, respectively, have been observed (table 1). Time-trend general population studies during periods of observed decay have reported half-lives in similar ranges.

However, it should be noted that the interindividual variation in elimination of PFASs can be substantial in both high and low exposure ranges, as observed in retired fluorochemical workers and after drinking water exposure.4 5 Observational data and pharmacokinetical modelling indicate that PFAS half-life is likely to be shorter in women, explained partly by menstrual blood losses, but there may also be other sex-specific elimination mechanisms.6 Except for perfluorobutane sulfonic acid, which has a much shorter half-life, around 1 month,7 there are no human data after end of exposure for other PFASs.

Ronneby: a case study from Sweden

In autumn 2013 a survey of groundwater quality in Blekinge county in southern Sweden showed alarmingly high levels of PFASs in groundwater from a glaciofluvial water reservoir, the Bredåkra delta, which has a military and civil airfield located in its centre. Extended water sampling revealed very high levels of PFASs in outgoing drinking water from Brantafors, one of the two municipal waterworks in Ronneby, a municipality with 28 000 inhabitants (table 2). This waterworks provided drinking water to one-third of the households in Ronneby. The contaminated waterworks was closed on 16 December 2013, and clean water was promptly provided by Kärragården, the second waterworks in the municipality. After a few days no elevated levels of PFASs could be detected in the distribution network. Brantafors waterworks was reopened in May 2014, supplied with new coal filters and using water only from wells with low PFASs levels, but the trial was ended in October 2014. During this trial the levels of PFASs (sum of 11) were closely monitored, reaching at most 40 ng/L (ie, well below 90 ng/L, the present Swedish recommended action level).

It was soon confirmed that the fire drill site at the nearby military airport localised within the aquifer area had leached PFASs to the environment. Despite considerable efforts from the Armed Forces, it has not been possible to reconstruct the detailed historical use of AFFF at the airfield, but the best estimate as to the start of the use of these foams is the mid-1980s. Very little information on past or current PFAS content in the foams used at the facility was available, only that PFOS-containing foams were not purchased since 2004. For a general overview of AFFFs, see refs 1 and 8.

Extensive biomonitoring in the municipality population started in June 2014, approximately 6 months after end of exposure through drinking water, by open invitations and free of cost. Subjects living and working in the contaminated as well as in the uncontaminated district were invited. During the period 2014–2016 a total of 3418 persons from Ronneby participated. Considerable efforts were made to recruit persons with little exposure to the contaminated water, in order to ensure a broad range of serum PFASs levels for further research on health effects. A reference group of 242 subjects from a nearby unexposed municipality (Karlshamn) was also examined in 2016.

Discussion

Among 106 persons observed between 6 and 33 months after end of exposure to PFAS-contaminated drinking water, the shortest half-life was observed for PFOA with a mean of 2.7 years. The half-life for PFHxS was twice as long, 5.3 years, and for PFOS the mean was 3.4 years. These results are somewhat shorter than the prior results for PFOS and PFHxS, based on observations in 24 retired fluorocarbon workers, to our knowledge the only other study that hitherto has reported apparent half-lives for PFOS and PFHxS after end of exposure that was substantially higher than the general population background.4 The retired workers, all but two men, were older than our population, had higher serum levels of PFOA and PFOS, and were followed for a longer period, 5 years. For PFHxS, the apparent half-life has been estimated to be 15.5 years in a recent study from a community with residential exposure to PFAS.11 The PFHxS levels in serum in that study were much lower than in our study, that is, 6.4 ng/mL vs 152 ng/mL. Furthermore, their population still had ongoing exposure, and a pharmacokinetic modelling approach based only on water intake was used to account for ongoing exposure. In our study, the background exposure was not subtracted when modelling half-life since the exposure levels in the general population from all sources were negligible compared with earlier drinking water intake in the study population. Our estimate of apparent half-life, which was obtained after a documented abrupt end of the dominating source of exposure, is thus a reliable estimate of the actual half-life of PFHxS.

Our estimate of apparent half-life for PFOA is in the range of values reported from five studies with averages ranging from 2.3 to 3.94 years, observed in fluorocarbon workers4; studies in populations living in PFOA-polluted areas around production plants, followed for 1–2 years after provision of clean drinking water5 12; occupationally exposed ski waxers13; and a study in a community exposed residentially to PFAS.11 For PFOS, the population half-life has been estimated to be 4.3 years from studies in US blood donors reflecting general population reduction in exposure.14 After an abrupt end of a dominating source of exposure, as in Ronneby, the finding of a shorter apparent half-life is as expected.

The interindividual variation in half-life was substantial, with a threefold difference between the 5th and 95th percentiles in each of the three PFAS, plus a few extreme outliers with extremely long half-lives. Large interindividual differences were also observed in retired fluorocarbon workers4 and in the general population after end of drinking water exposure.5 12 The variability between individuals, and between men and women, has not yet been adequately explained.

Blood loss due to menstruation accounts partly for a shorter elimination half-life in women, and was estimated to account for 30% of the discrepancy in elimination of PFOS between men and women.6 In this respect, the marked gender difference in elimination of PFHxS, as observed in our study and by Brede et al 5 but not for PFOA (our study and Bartell et al 12), with PFOS in between, is intriguing. Elimination pathways that are sex-specific and substance-specific appear to exist.

Reabsorption by OATs in the kidneys and extensive uptake from enterohepatic circulation for PFOS and PFOA are active processes that may differ between individuals, but also between different PFASs. An increased renal PFAS elimination at high doses indicates a capacity-limited, saturable renal resorption process via high-efficiency OATs,15 16 which may have sex-different expression.17 Moreover, in a PFOA-exposed US population, the excretion rate was related to polymorphisms (single-nucleotide polymorphisms; SNPs) in tubular transporter proteins.18 Faecal elimination is little studied in humans, with the exception of some case reports that indicate that cholestyramine, a lipid-lowering pharmaceutical, may enhance elimination.19

In addition to differences between individuals as to excretion capacity, recent data using paired human serum and urine samples for estimation of T½ have indicated marked differences between excretion of PFASs with different chain-length and isomers.20 It is likely that linear isomers are preferentially retained,21 but observational longitudinal human data on the excretion of linear versus branched chain isomers are absent. Thus, variation of T½ between populations and between individuals using total PFOS, PFOA and PFHxS determinations (as in this study) may in part reflect body burdens with different isomer composition.

Such differences are likely to be found in humans, given the varying production methods of PFAS over time. Synthesis of PFAS is by electrochemical fluorination or fluorotelomerisation. Electrochemical fluorination was used from the 1950s until the early 2000s and yielded branched and linear isomers. By contrast, fluorotelomerisation, which was later introduced, produces almost exclusively linear compounds.22 The firefighting foams used over time have differed in composition, but there may also be varying fate of different PFAS structural isomers during soil and groundwater transportation. Thus, it is of importance to include determination of both linear and branched isomers of PFOS, PFHxS and PFOA in order to understand differences in observed half-lives. Refined estimates of the half-lives of PFAS compounds and the important denominators of variance are needed to reconstruct historical exposure for epidemiological studies as well as to project future exposures for risk assessment.

Out of the hundreds of PFAS compounds now available, only PFOS is internationally regulated according to the Stockholm Convention, and PFOA is on the candidate list. The human data on PFHxS uptake and elimination are hitherto very limited. The present observations confirm the long persistence of this compound after end of external exposure—a rough extrapolation based on the mean half-life indicates that 10-year-old children from the contaminated water district cannot expect to attain the same PFHxS levels as their peers in the neighbouring town of Karlshamn until the age of 60–70. Thus, even after prompt end of external exposure, AFFF contamination of drinking water can result in very high exposure levels in a life-course perspective in local general populations. Hence, the need for precautionary regulations for classes of PFASs is imperative.

Limitation

The main limitation of the present first analysis is that the serum samples were analysed during a 2-year period and each individual’s samples were not analysed in the same batch. All samples were analysed at the same laboratory with the same methods and work-up procedure. However, there is a need to reanalyse all samples from each individual in the same batch to reduce laboratory variation, especially when determinants for variation in half-lives are investigated. This is planned as a next step in our studies.