The serum levels in the present study are similar to or lower than the levels found in a previous study on 17 Swedish human plasma samples collected in 1998–2000 from men and women (Karrman et al. 2004
). The Swedish PFOS and PFOA blood levels are similar to levels in, for example, Canada, Australia, and some less-industrialized regions in Japan, but somewhat lower than reported blood levels in the United States (Harada et al. 2004
; Karrman et al. 2006a
; Kubwabo et al. 2004
; Olsen et al. 2003
Only one study originating from China has previously reported levels of several PFCs in human milk. The Swedish levels are comparable to human milk from China except for those for PFOSA, which was not included in the Chinese study (So et al. 2006
). In addition to detected PFCs in the present study, PFHpA, PFDA, and PFUnDA were also found in human milk from China.
PFOSA was frequently detected in the milk samples, unlike PFNA, PFDA and PFUnDA, even though the latter were detected at higher concentrations in the serum samples. This is most likely caused by the fact that PFOSA concentrations in plasma have been found to be only about 20% of the whole blood concentration on a volume basis (Karrman et al. 2006b
). The total blood concentration of PFOSA available for excretion to milk is therefore about five times higher than the measured concentration in serum. The M:S ratio for PFOSA should therefore be close to that of PFOS if nearly all PFOSA were distributed to serum. The serum and milk pattern suggests that PFHxS is excreted to milk in a higher degree than PFOS and PFOSA. A preferential excretion of shorter, less hydrophobic PFCs is a possible explanation of the observed pattern, but could not be concluded in the present study because of the limited number of matched milk and serum samples.
The presented linear relationship between serum and milk levels suggests a partitioning process, which can be predicted from the PFC blood concentration on a volume basis. The steeper slope of PFHxS demonstrates the higher partition than PFOS to milk (). The association between milk and serum concentrations could not be seen for PFOSA (r2
< 0.1). The PFOSA ratio between milk and serum can be influenced by several parameters. First, it has been suggested that PFOSA can degrade to PFOS in biologic systems (Tomy et al. 2003
), which might affect the ratio between milk and serum. Second, PFOSA is partly lost during the separation of the red blood cells, which makes serum a poor matrix for determining PFOSA blood concentrations. Finally, relatively more milk and serum samples had levels of PFOSA close to the detection limit.
For more fat-soluble, persistent organohalogens, the levels in blood and milk are about the same when calculated on a fat basis and with a steady state assumption. On a volume basis, the ratio of lipophilic compounds in whole blood and milk is approximately 1:10, because of the higher lipid content in milk than in blood (Jensen and Slorach 1991
). The lactational transfer of PFCs may be more similar to that of heavy metals. For example, the concentration of lead in milk has been found to be 5–10 times lower than that in blood (Jensen and Slorach 1991
). Perfluorinated acids are generally believed to bind to serum albumin (Jones et al. 2003
). It has been demonstrated that serum albumin in plasma has a large binding capacity for PFOA (6–9 binding sites per molecule and millimolar concentration in plasma) and the free fraction of PFOA in plasma was estimated to be < 5% (Han et al. 2003
). The reason for the relatively higher PFC concentration in human serum than in milk is unknown.
Excretion of PFCs into milk may be accomplished by two ways that have been identified as transport mechanisms for chemical contaminants: binding to milk protein (protein content ~ 1 g/100 mL milk) or to the surface of fat (fat content ~ 4 g/100 mL milk) (Jensen and Slorach 1991
). The fat content in milk fluctuates but does not vary significantly during the course of lactation, unlike the total protein content, which was shown to decrease rapidly during the first month of lactation. The serum albumin content of milk was, however, stable during a 6.5-month period of lactation (Lönnerdal et al. 1976
). Assessing the amount of PFCs transferred and adsorbed by an infant during the course of lactation involves several assumptions—for instance, the variation of PFC concentration in milk with time and the uptake efficiency of PFCs from milk by the infant. The total mean PFC concentration of all detected compounds in the present study was 32 ng/mL in serum and 0.34 ng/mL in milk. Hypothetically, a lactation of 600 mL/day and 100% uptake would produce an exposure burden for an infant (and maternal excretion) of 203 ng PFCs per day, corresponding to 34 μg PFCs after 6 months, given a constant PFC concentration in milk during 6 months. A risk assessment is unfeasible because of the lack of human hazard assessment of each of the detected PFCs and of relevant reference intake levels or concentrations to compare with. However, So et al. (2006)
used a reference dose (25 ng/kg/day) for PFOS estimated by the Environmental Working Group, based on the end point of increase in mammary fibroadenomas in a rat chronic toxicity study (Thayer and Houlihan 2002
). Using the same assumptions (milk consumption 600 g/day, body weight 7 kg), two milk samples with the highest PFOS concentration in our study (0.465 and 0.337 ng/mL) exceed the reference dose and would therefore constitute a risk to the infant. However, there are several uncertainties that need clarification before any conclusions can be made.
This study contributes to PFC exposure risk assessments for infants, and the evaluation of lactation as an exposure pathway as well as a way for maternal excretion. Several studies indicate that females have lower blood concentrations of several PFCs than do males (Calafat et al. 2006a
; Karrman et al. 2006a
; Olsen et al. 2003
). Elimination through lactation could be one explanation for this observation. However, a sex difference was observed also for 2- to 12-year-old children in the United States (Olsen et al. 2004
PFOS and PFHxS were detected in composite milk samples collected each year between 1996 and 2003–2004 from four different regions in Sweden (). The variation of PFOS and PFHxS in the composite samples is remarkably small (a total variation of 20% and 32% CV, respectively), indicating that milk levels of PFOS and PFHxS have been constant in the last 8 years. Consequently, no clear temporal trend could be distinguished (). However, the samples from 2001, 2003, and 2003–2004 were from regions different from the rest of the samples. Possible regional differences in human PFC levels in Sweden remain yet to be established. PFOS has been present in the Swedish environment at least since 1968, and the levels increased dramatically up to 1997 in guillemot eggs (Holmström et al. 2004
). PFOS-related products were imported in Sweden until 2002 and will probably be used for a long period of time [KEMI (Swedish Chemicals Agency) 2004
]. The global production of perfluorooctanesulfonyl fluoride started to decrease in 2001 after the phase-out decision by the major producer 3M (3M 2000
). A possible effect of the actions taken by governments and producers in terms of declining environmental and human concentrations needs to be monitored for several years to come because of the persistence of PFCs [PFOS half-life is approximately 5 years in humans (Olsen et al. 2005a
Temporal trend for (A) PFOS and (B) PFHxS in human composite milk samples from different regions in Sweden, 1996–2004.
The relatively low levels of PFCs present in the human milk samples challenged the analysis. By reducing the volume of the milk sample extracts by a factor of 100, required detection limits were achieved. As a consequence, traces in the procedural blanks were seen for several of the compounds monitored (). A confident quantification of PFOA in the milk samples was hampered by a high procedural blank contamination. PFOA is usually the second highest PFC found in human blood, except in Korea where PFOA levels have been reported to exceed those of PFOS (Kannan et al. 2004
). PFOA contributed up to 36% of the total PFC content in human milk from China (So et al. 2006
). The selectivity of the single quadrupole MS method was successfully verified with triple quadrupole MS/MS analysis. Qualitative comparison indicated that MS/MS analysis demonstrated on average 50% higher concentrations compared with the single quadrupole MS analysis. However, different preconcentration methods were used for the different instruments, and the differences seen between the methods can be multifactorial.