New insights on reproductive toxicants

Alberto Mantovani discusses new findings regarding reproductive toxicants, which was debated at the European Teratology Society Conference in September

The public, policy makers and scientists pay increasing attention toward the chemical hazards affecting human reproduction, the development of the unborn and newborn child and  the hormone control of these processes. Reproductive health is pivotal in order to sustain societal development along time; in the meanwhile, new scientific knowkedge challenges the usual views on how to protect human repeoduction from chemical hazards. This evolving scenario has consequences on how chemicals are regulated, used and controlled, and involves such diverse stakeholders as industry, agriculture, regulators, public health services, and the media.

The evolving and multi-faceted scenario of  reproductive toxicology has been thoroughly debated at the 45th annual meeting of the European Teratology Society (ETS, www.etsoc.com, Budapest, 4th–7th September 2017); indeed, ETS has the mission to promote and stimulate an interdisciplinary debate among scientists from Europe (and elsewhere) on risk factors for reproductive health.

Let’s look to the “hot” issues for toxicologists that were discussed in Budapest.

Reproductive toxicants

One emerging concern is how hormonally-active chemicals can affect brain development. While this action is recognized for thyroid hormones, also agents affecting steroids and stress hormones can impinge on neurobehavioural ontogenesis, as indicated by the recent insights on brain pathophysiology. Even the effects of thyroid-disrupting substances still need investigation. Indeed, the European Commission has recently promoted (Paris, March 2017) a workshop to discuss open issues, such as thyroid hormone changes in laboratory animals tas reliable predictors of human developmental hazards.

While for decades attention has been given maonly to adverse effects that are evident at birth, like birth defects, strong evidence indicates that long-term effects resulting from altered programming in utero are a major issue. In particular, the transplacental exposure to tumorigenic agents might increase the risk of cancer in adulthood and/or of infrequent childhood tumours like pediatric leukemias. Chemicals of concern include classical carcinogenic contaminants (eg., air pollutants, combustion-derived substances), as well as agents acting at epigenetic and/or endocrine level. Upon recognition that such a problem does exist, the relevant questions are how a transplacental carcinogenesis potential should be identified in testing strategies for chemicals as well what molecular biomarkers could be used in epidemiological mother-child studies.

Chemical hazard investigation

Our societies require that investigation on chemical hazards must adress their assessment and regulation. In Europe, reproductive toxicants feature prominently amongst the “Substances of Very High Concern”  within the REACH  regulation on chemicals, implemented by the European Chemicals Agency. A robust assessment process fully exploiting scientific evidence is the ideal goal: therefore, the meaningful integration of the (often abundant) existing information is a key scientific challenge. The international scenario looks with great interest to the IATA (Integrated Approaches to Testing and Assessment) approach: IATA integrate the mechanistic information derived from large screening programmes, like the U.S. ToxCast, the predicted links between molecular/cellular targets and adverse effects (“Adverse Outcome Pathways”) and the information on internal exposure and metabolism (eg., how much a substance and/or its active metabolite(s) reach target fetal tissues). IATA are most attractive, but need implementation (learning by doing) in order to build a consistent, controlled and efficient process. Sure, IATA could be pivotal for using information from data-rich substances to predict (“read-across”) toxicological patterns of the, still numerous, data-poor chemicals.

The topics of ETS Conference were not limited to toxicology, featuring also research on pre-term births and the use of herbal drugs in pregnancy: ETS has also implemented the collaboration with ENTIS (the European Network of Teratology Information Services), in order to strengthen the links between experimental research and the clinical and epidemiological sectors. As every year,  Reproductive Toxicology, the ETS reference journal, has published a special issue (September 2017) dedicated to the Conference and its topics.

 

Alberto Mantovani,

Istituto Superiore di Sanità, Roma, Italy

alberto.mantovani@iss.it

Endocrine Disupters: http://www.iss.it/inte

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