Risk to human health related to the presence of perfluoroalkyl substances in food

Abstract

The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances (PFASs) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Panel decided to perform the assessment for the sum of four PFASs: PFOA, PFNA, PFHxS and PFOS. These made up half of the lower bound (LB) exposure to those PFASs with available occurrence data, the remaining contribution being primarily from PFASs with short half-lives. Equal potencies were assumed for the four PFASs included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and 'other children' showed a twofold higher exposure. Upper bound exposure was 4- to 49-fold higher than LB levels, but the latter were considered more reliable. 'Fish meat', 'Fruit and fruit products' and 'Eggs and egg products' contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL ₁₀ of 17.5 ng/mL for the sum of the four PFASs in serum was identified for 1-year-old children. Using PBPK modelling, this serum level of 17.5 ng/mL in children was estimated to correspond to long-term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake (TWI) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panel concluded that parts of the European population exceed this TWI, which is of concern.

Keywords: PBPK; PFAS; exposure; food; immune system; mixtures; risk assessment.

Figure 1

General structure of PFASs

Figure 2

Distribution of the limits of quantification (LOQs) of PFASs for reported results before (upper figure) and after (lower figure) applying the LOQ cut‐off

1. Box plot showing whiskers at minimum and maximum, box at P25 and P75 with line at P50, outliers shown as dots. The vertical green line shows the 1 μg/kg LOQ cut‐off, applied to most foods categories except drinking water (0.01 μg/kg) and ‘Edible offal, game animals’ and ‘Fish offal’ (no cut‐off).

Figure 3

Distribution of analytical results for PFASs divided by sampling country

Figure 4

Distribution of analytical results for PFASs divided by sampling year

Figure 5

Percent contribution of each perfluoroalkyl substance (PFAS) to total exposure to 17 PFASs in adults

Figure 6

Mean LB exposure from different food categories of adults (A, left) and toddlers (T, right) to PFOA, for various surveys

1. LB: lower bound; PFOA: perfluorooctanoic acid.

Figure 7

Mean LB exposure from different food categories of adults (A, left, inserted with different scale as toddlers) and toddlers (T, right) to PFNA, for various surveys

1. LB: lower bound; PFOA: perfluorooctanoic acid; PFNA: perfluorononanoic acid. Note: It should be stressed that the exposure from food for infants and small children was based on only one quantified level in 10 samples. This sample had a quantified PFNA level above the mean in liver from farmed animals, and PFOS or PFOA were not detected in the same sample, which is unexpected.

Figure 8

Mean LB exposure from different food categories of adults (A, left) and toddlers (T, right) to PFOS, for various surveys

1. LB: lower bound; PFOS: perfluoroheptane sulfonate.

Figure 9

Mean LB exposure from different food categories of adults (A, left) and toddlers (T, right) to PFHxS, for various surveys

1. LB: lower bound; PFHxS: perfluorohexane sulfonic acid.

Figure 10

The relative contribution of various perfluoroalkyl substances (PFASs) based on medians of median serum concentrations in biomonitoring studies in Europe for adults presented in Tables 16 and 17 and for children presented in Tables 18 and 19

Figure 11

Absolute liver weights in male rats exposed to various PFASs, based on applied dose (left) or serum levels (right)

1. PFAS: perfluoroalkyl substance; PFBS: perfluorobutane sulfonic acid; PFOS: perfluoroheptane sulfonate. For WY‐14,643 serum levels were not determined. There is a clear shift in the order of the different PFASs; compare e.g. PFBS (blue dots) and PFOS (red dots).

Figure 12

Estimated serum levels of perfluorooctanoic acid (PFOA) in a woman exposed in utero, via breastfeeding for 12 months and subsequently via food intake for 49 years to 0.187 ng/kg bw per day

1. The level peaks at 9 months of breastfeeding around 9.1 ng/mL, decreases and then increases to 2.0 ng/mL at 35 years and a steady state level at 50 years around 2.1 ng/mL.

Figure 13

Estimated serum levels of perfluoroheptane sulfonate (PFOS) in a woman exposed in utero, via breastfeeding for 12 months and subsequently via food intake for 49 years to 0.444 ng/kg bw per day

1. The level peaks at the end of breastfeeding around 8.7 ng/mL, decreases and then increases to 4.9 ng/mL at 35 years and a steady state level at 50 years around 5.5 ng/mL.

Figure 14

Estimated serum levels of perfluorooctanoic acid (PFOA) in a child exposed in utero, via breastfeeding for 12 months and subsequently via food intake for 9 years to 0.374 ng/kg bw per day (exposure from food twofold that of the mother)

1. The level peaks at 9 months before the end of breastfeeding around 9.1 ng/mL, decreases and then reaches levels of 8.8, 2.4 and 2.6 ng/mL at, respectively, 1, 5 and 10 years of age. Estimated levels of PFOA in children who are not breastfed are also shown (none).

Figure 15

Estimated serum levels of perfluoroheptane sulfonate (PFOS) in a child exposed in utero, via breastfeeding for 12 months and subsequently via food intake for 9 years to 0.888 ng/kg bw per day (exposure from food twofold that of the mother)

1. The level peaks at the end of breastfeeding around 8.7 ng/mL, decreases and then reaches levels of 4.2 and 5.1 ng/mL at, respectively, 5 and 10 years of age. Estimated levels of PFOS in children who are not breastfed are also shown (none).

Figure 16

Estimated daily intake of PFOA/PFNA, PFHxS/PFOS or the sum of 4 PFASs during the first 2 years considering exposure breastfeeding for the first 12 months of life and thereafter from food

1. Exposure from food during the second year was 0.374 and 0.888 ng/kg bw per day for PFOA/PFNA and PFHxS/PFOS, respectively, being twice that of the mothers. Serum levels of the mother at 35 years were 2.00 and 4.89 ng/mL for PFOA/PFNA and PFHxS/PFOS, respectively. Based on milk/serum ratios of 0.015 and 0.03, this resulted in initial milk levels of 0.073 and 0.060 ng/mL for PFOA/PFNA and PFHxS/PFOS, respectively. These levels were modelled to decline with 7.7 and 3.1% each month for PFOA/PFNA and PFHxS/PFOS, respectively.

Figure H.1

PFC response in male B6C3F1 mice treated with 0, 0.005, 0.05, 0.1, 0.5, 1 or 5 mg PFOS/kg bw (TAD) for 28 days by oral gavage (n = 5)

1. * Significantly different from control (p < 0.05). (Mean and SEM). Two independent experiments.

   PFC: perfluorinated compound; PFOS: Perfluorooctanesulfonic acid; SEM: standard error of mean; TAD: total applied dose.

Figure H.2

PFC response in female B6C3F1 mice treated with 0, 0.005, 0.05, 0.1, 0.5, 1 or 5 mg PFOS/kg bw (TAD) for 28 days by oral gavage (n = 5)

1. * Significantly different from control (p < 0.05). (Mean and SEM). Two independent experiments.

   PFC: perfluorinated compound; PFOS: Perfluorooctanesulfonic acid; SEM: standard error of mean; TAD: total applied dose.

Figure H.3

PFC response in female C57Bl/6 mice (WT) and PPARα targeted mutation mouse model (MUT; Taconic), treated with PFOS for 28 d by gavage, with N = 5 (mean, SEM)

1. * Significantly different from control (p < 0.05). Samples were blinded to person reading slides. Doses of 0, 0.5 and 5 mg/kg bw (TAD).

   PFC: perfluorinated compound; PFOS: Perfluorooctanesulfonic acid; SEM: standard error of mean; TAD: total applied dose.

Figure K.1–K.3

Scatter plot of levels of vaccine antibodies (K.1 Hib, K.2 Tetanus, K.3 Diphtheria) adjusted for the number of vaccinations (in the case of tetanus only) and for the time since the last vaccination for Hib (K.1, n = 98), tetanus IgG1 (K.2, n = 100) and diphtheria (K.3, n = 100), in relation to the PFAS sum (PFOA, PFNA, PFHxS and PFOS) levels

1. Titres are presented as log 10 transformed values. Broad grey band: moving average; red line: Fitted ‘knee’ function; horizontal green line: mean minus one standard deviation of the antibody levels below the ‘knee’; vertical grey line: PFAS sum level of the ‘knee’; vertical blue line: PFAS sum level of the ‘knee’ function with antibody levels averagely diminished by one standard deviation.

Figure K.4

Relative contribution of PFOA, PFOS, PFNA and PFHxS to the PFAS sum in the quintiles

Figure K.5

Empirical cumulative distribution functions of PFAS sum (PFOA, PFNA, PFHxS and PFOS) quintiles together with the respective fitted normal distribution curves

1. Titres on the X‐axis presented as log 10 transformed values.

Figure M.1

Body weight curves influence on PFOA serum concentration (ng/mL)

1. CA1 corresponds to equation used in the current opinion (French survey), CA2 to the WHO curve (P50 in boys), CA3 to the WHO curve (P50 in girls).

Figure M.2

Body weight curves

1. BW1 represents the body weight curve from the French survey (used in the current opinion), BW2 the body weight curve from P50 WHO curve for boys and BW3 the body weight curve from P50 WHO curve for girls.

Figure M.3

Body weight curves influence on PFOA serum concentration (ng/mL)

1. CA1 corresponds to equation used in the current opinion (French survey), CA2 to the WHO curve (P50 in boys), CA3 to the WHO curve (P50 in girls).

Figure M.4

Comparison of model PFOA simulation with experimental data from Emmett et al. (2006) used by Loccisano et al. (2011) for validation