Table B.1.

Time trends for PFASs in blood and breast milk

Period	Study population	Country	PFASs	Trend	Reference
European time trend studies
1987–2007	n = 80 plasma samples women, sampled in connection with breast reduction surgery (1987–1991), or as wives of men with cancer (2006–2007) mean age (range): 48 (36–56) years Cross sectional	Sweden	PFHxS, PFOS, PFOA, PFNA, PFDA, PFUnDA	PFHxS, PFOS and PFOA peaked during the period 1990–2000. PFHxS increased during the whole period. PFOS and PFOA decreased from around 2000, even though only PFOS was significant. PFNA, PFDA and PFUnDA increased during the whole period, largest increase after the year 2000	Axmon et al. (2014)
1972–2008	n = 20 pools of breast milk healthy native Swedish mothers at the Mothers’ milk center in Stockholm cross sectional	Sweden	PFOS, PFOA, PFHxS	Concentrations of PFOS, PFOA and PFHxS increased from 1972 to the 1990s. From around 2001 to 2008 the concentrations of all three PFASs decreased, while the trend for PFHxS was not significant	Sundström et al. (2011)
1996–2010	n = 36 pools of serum primiparous women living in Uppsala County, donated serum samples within the third week after delivery age: 19–41 years cross sectional	Sweden	PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFTeDA, PFBS, PFHxS, PFOS, PFDS, FOSA	PFBS, PFHxS, PFNA and PFDA increased during the period 1996–2010, while PFOS, PFDS, FOSA and PFOA decreased in the same period. For PFHpA and PFUnDA, no significant trend was observed. PFHxA, PFDoDA, PFTrDA and PFTeDA were not detected in any sample above LOQ. The increasing trends of PFBS and PFHxS have later been shown to be due to contamination of drinking water with these PFASs (Gyllenhammar et al., 2013)	Glynn et al. (2012)
1997–2012	n = 27 pools of serum (three pools at each time point) primiparous women living in Uppsala County, donated serum samples within the fourth week after delivery cross sectional	Sweden	PFBS, PFHxS (branched and linear), PFOS (branched and linear), FOSA (branched and linear), EtFOSA, PFHpA, PFOA (branched and linear), PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA,, 8:2/8:2 diPAP	Significant decreasing trends were observed for branched and linear PFOS, PFDS, branched and linear FOSA and for PFOA. Significant increasing trends were observed for branched and linear PFHxS, PFNA, PFDA, PFUnDA, PFDoDA and PFTrDA. No significant trends were observed for PFBS, and 8:2/8:2 diPAP. While EtFOSA, was detected in less than 60% of the samples and thus no statistical calculations were made	Gebbink et al. (2015)
1974–2010	Archived serum samples from Swedish primiparous women living in the Uppsala county (n = 36 pools between 1996 and 2010) Archived American serum or plasma samples from 1974, 1989, 2000/2001, 2006 and 2010 were collected from individuals residing in the Hagerstown, Maryland (n = 60) cross sectional	Sweden and USA	PFOS, PFOS isomers and 1‐m PFOS enantiomers	Swedish population: For ΣPFOS; No significant trend was seen up to 2000, but between 2000 and 2010 a downward trend was observed. For % branched PFOS; no significant trend was found between 1996 and 2000, but a significant upward trend was seen between 2000 and 2010. For the enantiomeric fraction of 1‐m PFOS; a significant decreasing temporal trend was observed between 1996 and 2000, but no significant trend was seen between 2000 and 2010 American population: For ΣPFOS; No significant temporal trend was found for from 1974 to 2000/2001, but in the 2000/2001–2010 period, the downward trend was seen. For % branched PFOS; no significant trend was found for the period 1974–2010. For the enantiomeric fraction of 1‐m PFOS; no significant temporal trend was observed	Liu et al. (2015)
1996–2004	n = 9 pools from Swedish primiparous women with a median age ranging from 27 to 30 years for the various pools cross sectional	Sweden	PFHxS, PFOS, FOSA, PFOA and PFNA	PFOA and FOSA were not observed above LOQ in any samples while PFNA was only found in three samples in similar concentrations. Quite stable concentrations were observed for both PFHxS and PFOS between 1996 and 2000, while a slight decrease was observed in 2003–2004 for PFHxS and in 2002–2004 for PFOS	Kärrman et al. (2007)
2001–2014	n = 579, men and women, 70 years (2001–2004), 75 years (2006–2009) and 80 years (2011–2014) at the three sampling time points, serum longitudinal sampling	Sweden	Fourteen PFASs, whereof trends were evaluated for the following: PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFHxS, PFOS, FOSA	The concentrations of all PFASs except FOSA and PFOS increased from the first to the second sampling. Between the two last samplings, the concentrations decreased for all PFASs	Stubleski et al. (2016)
1972–2016	n = 20 pools from Stockholm (9–116 individuals per pool), women, breast milk	Sweden	PFPeA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFTeDA, PFPeDA, PFBS, PFHxS, PFOS, PFDS, FOSA, MeFOSAA, EtFOSAA	PFOS, PFOA, PFHxS and PFNA increased from 1972 but decreased from 1988, 2000, 2004 and 2010, respectively. PFUnDA increased throughout the whole period, while PFTrDA, PFBS and PFHxA decreased from 1972 to 2004, 2011 and 2011, respectively, before increasing until 2016. No trends were observed for PFHpA and PFDoDA	Nyberg et al. (2018)
2007–2015	n = 11 pools from Gothenburg (5–11 individuals per pool), women, breast milk	Sweden	PFPeA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFTeDA, PFPeDA, PFBS, PFHxS, PFOS, PFDS, FOSA, MeFOSAA, EtFOSAA	PFHxS, PFOS and PFDoDA decreased significantly from 2007 to 2015. None of the other PFASs showed any statistically significant trends	Nyberg et al. (2018)
1977–2006	n = 24 pools of serum males 40–50 years cross sectional	Norway	Nineteen PFASs, whereof trends were evaluated for the following 13: PFPeA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFBS, PFHxS, PFHpS, PFOS, FOSA	PFOA, PFNA, PFDA, PFUnDA, PFHxS, PFHpS and PFOS all increased from the mid‐1970s up to the mid‐1990s, while FOSA reached a plateau between 1985 and 1993. The concentrations of PFOS, PFOA and PFHpS decreased from around 2,000, while for FOSA the decrease started somewhat earlier. No particular trends were observed for PFNA, PFDA and PFUnDA after around 2,000. The concentrations of PFPeA, PFHpA, PFDoDA and PFTrDA were quite stable during the whole study period	Haug et al. (2009)
1979–2007	n = 254 serum samples from 53 males from Northern Norway median age at first and last sampling was 43 and 71 years, respectively repeated sampling and measurements at up to five time points (1979, 1986, 1994, 2001 and 2007) longitudinal sampling	Norway	Ten PFASs were quantified, from which trends were assessed for eight: PFOA, PFNA, PFDA, PFUnDA, PFHxS, PFHpS, PFOS, FOSA	Increasing trends were observed for all the eight PFAS from 1979 and onwards. For PFOS, PFOA and FOSA, significant decreasing concentrations were observed from 2001 to 2007. In contrast, increasing concentrations were observed throughout the whole study period for PFNA, PFDA and PFUnDA, while only the trends for PFNA and PFDA were statistically significant for all time periods. Similar concentrations of PFHxS were observed in 2001 and 2007. Somewhat lower concentrations of PFHpS were observed in 2007 when compared to 2001, but this trend was not significant	Nøst et al. (2014)
2008–2013	n = 1,533 serum samples pregnant nulliparous women from the Aarhus Birth Cohort Biobank most participants gave a blood sample between 11 weeks and 14 weeks of gestation median age 29 years cross sectional	Denmark	Sixteen PFASs; whereof trends were assessed for PFASs detected in > 50% of the samples, i.e. PFHxS, PFHpS, PFOS, PFOA, PFNA, PFDA, PFUnDA	All seven PFASs decreased in the period 2008–2013	Bjerregaard‐Olesen et al. (2016)
1982–2010	n = 258 plasma samples from the German Environmental Specimen Bank males and females, approximately 50% of each age range 20–29 years cross sectional	Germany	PFBA, PFPeA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFTeDA, PFBS, PFHxS, PFHpS, PFOS, PFDS	PFTrDA, PFTeDA, PFBS, PFDS not found in any samples. For PFBA, PFPeA, PFHxA, PFUnDA and PFDoDA, only very few samples had concentrations above LOQ. PFHpA, PFDA and PFHpS were quantifiable in 20–30% of the samples PFOS increased from 1982 to 1986, and remained quite stable up to 2001. From 2001 to 2010, a steadily decrease has been observed. PFOA concentrations also increased from 1982 to 1986 were quite stable up to 2008 and decreased from 2008 to 2010. PFHxS increased from 1982 to 2001, was stable up to 2005 and decreased after that. For PFNA, no trend was observed	Schröter‐Kermani et al. (2013)
1982–2009	n = 420, students, male and female 20–29 years from Halle and Munster cross sectional	Germany	PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFTeDA, 8:2 diPAP	From 2000 to 2009, the concentrations of PFOA decreased, while the concentrations of PFNA, PFDA and PFUnDA increased in the same period. No significant trend was observed for 8:2 di‐PAPs throughout the same period	Yeung et al. (2013a)
1982–2009	n = 420, students, male and female 20–29 years from Halle and Münster cross sectional	Germany	PFOS, PFHxS	For some of the compounds increasing concentrations were observed during the first years of the study. From around 1995 to 2009, decreasing concentrations were observed for PFOS, while no clear trend was seen for PFHxS	Yeung et al. (2013b)
1977–2004	n = 30, students, 19 males and 11 female, 20–29 years from Arnsberg cross sectional	Germany	PFBS, PFHxA, PFPeA, PFOA, PFOS, PFHxS	PFOS and PFOA levels remained fairly stable throughout the period, while PFHxS concentrations increased during the whole study period	Wilhelm et al. (2009)
Examples of time trend studies in other countries
2003–2013	n = 71 persons. 81% of the participants were female Gullah African Americans participating in the SLEIGH study serum The age ranged from 6.1 to 77.6 years at the first visit longitudinal study; two time points	USA	Trends reported for PFHxS, PFOS, PFOA, PFNA, PFDA, PFUnDA	At a population level, an overall decrease in the concentration of PFOA, PFOS, PFHxS and PFUnDA was seen. No significant trend was observed for PFDA Some individuals had a considerable increase of PFHxS concentration from the first to the second blood sample, but for the overall population, the PFHxS concentration decreased	Gribble et al. (2015)
2003–2011	30 random samples from 2003, 2005, 2007, 2009 and 2011 (n = 150) pregnant women, between 28 and 32 weeks of gestation, who were enrolled in a prospective birth cohort study in Hokkaido (the Hokkaido Study on Environment and Children's Health) mean age: 30.3 years cross sectional	Japan	PFHxS, PFOS PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA and PFTeDA	Concentrations of PFOS and PFOA decreased during the period 2003–2011, while the levels of PFNA and PFDA increased in the same period. The trends for the remaining compounds were not significant	Okada et al. (2013)
2002–2011	n = 158 pools of serum males and females, aged from 0 to > 60 years four time points 2002/2003, 2006/2007, 2008/2009 and 2010/2011 cross sectional	Australia	PFDA, PFHxS, PFNA, PFOA, PFOS, FOSA	Decreasing trends were observed for PFOS and PFOA, while more variable trends were observed for the other PFASs and the various age groups	Toms et al. (2014)
2002–2013	n = 54 pools from 4,920 individuals, men and women, 0–> 60 years, serum cross sectional	Australia	8:2 diPAP, EtFOSA, EtFOSE, PFBA, PFPeA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFTeDA, PFHxDA, PFODA, PFHxS, PFOS, PFDS	Decreasing trends were observed throughout the entire period for PFHxS, PFHpS, PFOS and PFOA, while PFNA, PFDA and PFUnDA concentrations started to decrease from 2006. PFDoDA increased from 2006 and onwards	Eriksson et al. (2017)
1999–2008	n = 7,876 samples from the NHANES study age: ≥ 12 years, males and females cross sectional	USA	PFOS, PFHxS, PFOA, PFNA	The PFOS concentrations decreased significantly during the period, while the PFNA concentrations had a significant upward trend. The highest concentrations of PFOA were observed in 1999–2000, while the concentrations were quite stable from 2003 to 2008. Decreasing concentrations were observed for PFHxS in the period 1999–2006, but an increase has been observed in 2007–2008	Kato et al. (2011)