Chemicals and decreased immune response


Can certain chemicals weaken our resistance to infection, and perhaps pave the way for epidemics? Yes, it is possible: a growing number of both experimental and epidemiological studies indicate this to us. (1)

A very recent scientific paper, published by a group of U.S. researchers in March 2021 in the International Journal of Environmental Research and Public Health takes a further step in this direction. (2)

The study examined the use of the ToxCast system to identify substances that inhibit immunity. ToxCast, developed by the U.S. Environmental Protection Agency (USEPA), is a screening system that identifies the key toxicity mechanisms of chemicals, thereby allowing priorities to be identified for evaluation of possible health risks.

The case of the widespread additive in oils and fats

The team of researchers first examined a food additive, tert-butyl hydroquinone (TBHQ), used as a preservative for oils and fats. The substance was evaluated in 2004 by the European Food Safety Authority (EFSA), which, based on laboratory animal data available at the time, identified several toxic effects, but only at very high doses and without giving particular emphasis to some immune effects. (3)

However, screening using the ToxCast identifies the immune system as a potentially critical target for TBHQ, calling for a more up-to-date assessment.

PFAS immune response inhibitors

The study also considered perfluoalkyl substances (PFAS), unfortunately known for the serious case of contamination in Veneto, on which the Istituto Superiore di Sanità has also intervened. (4)

PFAS have been widely used in the past (fabric additives, in Teflon, etc.) and are very persistent contaminants. Unlike TBHQ, PFAS were recently evaluated by EFSA, which pointed to theinhibition of the immune response, observed in both laboratory and epidemiological studies, as the effect seen at the lowest doses and of greatest concern overall.

EFSA also concluded that PFAS levels in food in Europe are of concern. (5) Therefore, it is expected that-at last-controls for these contaminants will be initiated.

ToxCast fails on PFASs

Despite the evidence obtained in laboratory animals and in humans, screening using the ToxCast system surprisingly did not provide important signals of immunotoxicity for PFAS.

The researchers who authored the study draw two important conclusions:

1) The immunotoxic effects of chemicals are important and deserve more attention;

2) the ToxCast represents a state-of-the-art and potentially very useful screening for chemical toxicity, but it needs to be updated to more accurately capture immunotoxicity: its ineffectiveness against PFASs demonstrates this.

One Health Goal

This study further reinforces the new concept of One Health, in which chemical pollution risk and infectious risk should be viewed as factors that can, unfortunately, interact and develop synergies in environmental settings that do not adequately control these risks.

In addition, effects on the immune response must receive the attention they deserve in the safety evaluation of chemicals.

Alberto Mantovani


(1) Alberto Mantovani. Contaminants and infections: a link to explore. Open Access Government, 17.4.2020

(2) Naidenko, Olga V.; Andrews, David Q.; Temkin, Alexis M.; Stoiber, Tasha; Uche, Uloma I.; Evans, Sydney; Perrone-Gray, Sean. 2021. ‘Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food’. Int. J. Environ. Res. Public Health 18, no. 7: 3332.

(3) SEE

(4) Superior Institute of Health (ISS). Contamination by perfluoroalkyl substances in Veneto. Dietary exposure assessment and risk characterization

(5) See PFAS in food: EFSA assesses the risks and sets the safe limit. 17.9.20

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Toxicologist, research director of the Istituto Superiore di Sanità (ISS), former president of the European Society of Teratology. As well as historical member, for 15 years, of the scientific panel on feed and pesticides at EFSA (European Food Safety Authority) where he continues to work as an external expert.