ERF of PFAS

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Question

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

Rationale

Data

ERF of PFAS(-)

Obs	Exposure agent	Response	Exposure	Exposure unit	ER function	Scaling	Threshold	ERF	Description
1	PFAS	PFAS TWI	Maternal exposure via ingestion	ng /kg /wk	TWI	BW	0	4.4	EFSA 2020
2	PFAS	Immunosuppression2	Maternal ingested intake	ng /kg /wk	ERS	BW	0	0-0.0454	Converted from the row above assuming linearity and steady state
3	PFAS	Immunosuppression	Infant's blood concentratioin	ng /ml	RR	Log10	0.477 - 1.477	6.863 (1.473 - 36.01)	Grandjean, 2012
4	PFAS	Cholesterol increase	Ingestion	ng /kg /wk	ERS	BW	0	0	EFSA?
5	PFAS	Decreased birth weight	Ingestion	ng /kg /wk	ERS	BW	0	0	EFSA?
6	PFAS	Increased ALT	Ingestion	ng /kg /wk	ERS	BW	0	0	EFSA?

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.

Several studies show that increased PFAS compounds reduce the immunoresponse of diphteria, tetanus, or other vaccines. Some ERFs are listed here. Grandjean (2012) 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 the relationship between immunoglobulin concentration and and infection risk is linear, i.e. that 10 % decrease in immunoglobulin produces 10 % increase in risk of infection, we get the inverse of these numbers, i.e. the relative risk is 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, and this may be considered as a threshold for the effect. Another way to estimate a threshold is to look at NOAEC. A cohort with 101 infants from Germany found that the NOAECs for PFOA, estimated by dividing exposure into quintiles, ranged between 18.9 and 19.4 ng/mL, depending on the type of antibody titres. CONTAM panel identified an NOAEC at serum level at the age of 5 years for the sum of PFOA, PFNA, PFHxS and PFOS of 27.0 ng/mL. Therefore, there could be a threshold in a range of 3 - 30 ng/ml for sum of PFAS. That is equal to 0.477 - 1.477 on log10 scale. This may be a reasonable threshold for the response. A threshold is needed because the effects in EFSA report 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

+ Show code- Hide code # This is code Op_en7974/ERF_pfas on page [[ERF of PFAS]] # Note! This version has ERF and threshold in the same ovariable. library(OpasnetUtils) ERF_pfas <- Ovariable("ERF_pfas", ddata = "Op_en7974") colnames(ERF_pfas@data) <- gsub(" ", "_", colnames(ERF_pfas@data)) objects.store(ERF_pfas) cat("Ovariable ERF_pfas stored.\n")