Comment on “Maternal Exposure to Per- and Polyfluoroalkyl Substances (PFAS) and Male Reproductive Function in Young Adulthood: Combined Exposure to Seven PFAS”

Hærvig et al. report on inverse associations between maternal exposure to per-and polyfluoroalkyl substances (PFAS) during early pregnancy and parameters of semen quality in young adulthood, with a quite impressive number of participants (n = 864).1 However, I was surprised that Hærvig et al. 1 did not discuss co-exposures to other persistent organic pollutants (POPs), in particular polychlorinated dibenzo-p-dioxins and dibenzofurans (dioxins), given that a high correlation can be expected between internal dioxin and PFAS levels.Reduced sperm concentration in Western societies has been discussed for decades, but clear evidence with respect to causal factors is still missing.One of the hypothesized factors is an impact of POPs during critical windows of susceptibility for developmental effects in the perinatal period, for example, on Sertoli cells. 2 Dioxins, in particular, have been suspected agents ever since results began emerging from studies of cohorts exposed to very high levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin following the 1976 Seveso accident 3,4 ; a causal relationship is supported by animal data.5 In 2018, the European Food Safety Authority used data from a study of high ambient exposure in a Russian industrial city 6 to derive a tolerable weekly intake for dioxins below mean consumption levels observed in several countries.7 Both PFAS and dioxins accumulate in the food chain, and consumption of foods of animal origin especially leads to daily low-level background exposures, resulting in their accumulation in the human body.7,8 Therefore, a high correlation of PFAS and dioxin levels can be expected in the mother, fetus, and newborn, and most especially in the infant at the end of the first year of life, after several months of breastfeeding.However, published data are missing.In our study 9 of mother-child pairs when the children were 11 months of age, Spearman's rank correlation coefficients with plasma levels of dioxin International Toxicity Equivalents (I-TEq) were calculated to be 0.77 for perfluorooctanoic acid (PFOA) and 0.54 for perfluorooctane sulfonate (PFOS) (n = 74, p < 0:0001 in both cases).The correlation of levels of PFOA and dioxin I-TEq is displayed in Figure 1.The corresponding coefficients in the mothers were lower, but still highly significant (p < 0:0001).Levels of other lipophilic POPs, including polychlorinated biphenyls and legacy organochlorine pesticides, were also found to have a high correlation with levels of PFOA and PFOS.9 Notably, our study included maternal blood samples collected in the late 1990s,