ERF of PFAS

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Question

What are the exposure-response functions (ERF) of perfluorinated alkyl substances (PFAS) on several health endpoints?

Answer

Rationale

Data

ERF of PFAS(-)
ObsExposure agentResponseExposureExposure unitER functionScalingThresholdERFDescription
1PFASPFAS TWIMaternal exposure via ingestionng /kg /wkTWIBW04.4EFSA 2020
2PFASImmunosuppression2Maternal ingested intakeng /kg /wkERSBW00-0.0454Converted from the row above assuming linearity and steady state
3PFASImmunosuppressionInfant's blood concentratioinng /mlRRLog102.476.863 (1.473 - 36.01)Grandjean, 2012
4PFASCholesterol increaseIngestionng /kg /wkERSBW00EFSA?
5PFASDecreased birth weightIngestionng /kg /wkERSBW00EFSA?
6PFASIncreased ALTIngestionng /kg /wkERSBW00EFSA?

Immunosuppression is not well quantified. Here we assume that at the tolerable weekly intate (TWI) level, 0-20 % of respiratory infections are attributable to PFAS. Although age is not specified in the table, PFAS exposure is highest in infants due to pregnancy and breast feeding. Therefore we assume that immunosuppression occurs mainly at ages 0-9 a. The TWI comes from EFSA[1].

Several studies show that increased PFAS compounds reduce the immunoresponse of diphteria, tetanus, or other vaccines. Some ERFs are listed here. Grandjean (2012)[2] showed –39% (95%CI: –55, –17) and –21% (95%CI: –38, 1) decrease in diphtheria antibody concentrations at 5 years pre‐ and post‐booster, respectively, related to doubling of PFAS concentration (average 27.3 ng/ml in maternal serum). A twofold increase in maternal concentrations of combined PFOS, PFHxS, and PFOA during pregnancy was significantly associated with ‐48% (95%CI: –68, –16) and –42% (95%CI: –66, –1) decrease in serum antibody response to diphtheria at age 5 pre‐booster and age 7.5 post‐booster, respectively. No associations were observed for tetanus. The same analysis was done with offspring serum concentrations: A twofold increase in combined exposure at age 5.0 years pre‐booster was associated with a −44% (95%CI: −66, −11) and −55% (95%CI: −73, −25) decrease in serum antibody response to diphtheria and tetanus at age 7.5, respectively.

Not all PFAS compounds and not all vaccine responses showed systematic effect. However, several combinations do, so it is assumed here that the effect is real and is close to the ERF of infant's PFAS concentration on diphtheria. Percentage changes expressed as relative risks (RR) are 0.56 (0.34 - 0.89). Doubling of a concentration means log10(2) = 0.301 addition on a log10 scale. Therefore, the beta = ln(RR) should be multiplied by 1/0.301 to get change per one unit log10, i.e. ten-fold increase. This brings us to exp(ln(0.56)/log10(2)) = 0.146, exp(ln(0.34)/log10(2)) = 0.0278, and exp(ln(0.89)/log10(2)) = 0.679. If we assume that 10 % decrease in immunoglobulin produces 10 % risk in infection, we get the inverse of these numbers, i.e. 6.863 (1.473 - 36.01).

According to Infant's indirect exposure, 1 ng/d of mother's PFAS intake results in 0.056 ng/ml in infant's blood. Put the other way round, 1 ng/ml in infant's blood is a result of 17.8 ng/d intake by the mother. Similarly, the TWI intake of 4.4 ng/kg/wk * 70 kg / 7 d/wk = 44 ng/d results in 2.47 ng/ml in infant's blood. This may be a reasonable threshold for the response. A threshold is needed because the effects in EFSA report[3] are reported as X % decrease in the immunoglobulin concentration per doubling of the PFAS concentration. On a log x axis, this produces a straight line but, without a threshold, the immunoglobulin concentrations would theoretically increase to infinity as the PFAS concentration approaches zero. A practical threshold should be placed to an area that contains the lower levels of observed PFAS concentrations.

Calculations

Initiation 2021-01-29

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See also

References

  1. EFSA. (2020) Risk to human health related to the presence of perfluoroalkyl substances in food. https://doi.org/10.2903/j.efsa.2020.6223
  2. Grandjean P, Andersen EW, Budtz‐Jorgensen E, Nielsen F, Molbak K, Weihe P and Heilmann C, 2012. Serum vaccine antibody concentrations in children exposed to perfluorinated compounds. JAMA, 307, 391–397. https://doi.org/10.1001/jama.2011.2034
  3. Cite error: Invalid <ref> tag; no text was provided for refs named efsa2020