DIRECCIÓN GENERAL DE SALUD PUBLICA, CALIDAD
E INNOVACION
SUBDIRECCIÓN GENERAL DE SANIDAD AMBIENTAL Y SALUD LABORAL
Comments on the draft Commission Delegated Regulation setting out scientific criteria for the determination of endocrine-disrupting properties pursuant to Regulation (EU) Nº 528/2012
The Spanish Competent Authority for Biocide Regulation welcomes the possibility to comment the draft Commission Regulation on the scientific criteria for the determination of endocrine-disrupting properties and support the use of the WHO/IPCS definition for setting these scientific criteria. However, we have the following comments:
With regard to ANNEX, Section A 1., which includes the criteria for determining endocrine disrupting properties, we have the following observations:
According to the WHO definition, "an ED is a substance or mixture exogenous altering the function or functions of the endocrine system and consequently causes adverse effects in an intact organism, or its progeny, or (sub) populations" ( IPCS / WHO, 2002).
A substance may cause impaired function or functions of the endocrine system by many "modes of action" different. The term "mode of action" has been used by the IPCS to refer to how a substance interacts with a biological system to produce an adverse effect. In this context, the mode of action is defined as "biologically plausible sequence of key events, beginning with the interaction of a substance with a cell, through functional and anatomical changes that lead to a manifest effect, supported by strong experimental observations and data on the mechanism "(Boobis et al, 2009).
The concept of adversity in toxicology and the time when an observed change should be considered adverse is a subject of ongoing debate and the IPCS has adopted the following general non-specific definition of ED "a change in the morphology, physiology, growth, development, reproduction or life span of an organism, system or (sub) population that results in an impairment of functional capacity, impairment of the capacity to compensate for additional stress or an increase in susceptibility to other influences "(IPCS / WHO, 2009).
In the definition of ED WHO, the causal association between an impaired function of the endocrine system and the adverse effect it is provided by the term "and consequently causes". The expert advisory group on endocrine disrupters (ED EAG) recognized that, as arises in defining the requirement of absolute proof of causality would be a requirement too high to establish a substance as ED, and agreed that the convincing evidence of a biologically plausible link between the activity of the substance to cause endocrine disruption and an adverse effect observed was accepted.
In short, the ED EAG agreed that the elements for identifying an ED were demonstration of an adverse effect for which there was convincing evidence of a biologically plausible causal link to an endocrine disrupting mode of action and for which disruption of the endocrine system was not a secondary consequence of other non endocrine-mediated systemic toxicity. It is assumed that in the absence of appropriate data demonstrating no relevance, data of adverse effects in animals are relevant to humans.
In view of the above, we believe that this section should look like:
"An active substance shall be deemed to have endocrine disrupting properties with respect to humans if it is a substance that meets all the following criteria:
(1) causes an adverse effect in an intact organism, or its progeny, or (sub) populations, meaning adverse effect "a change in the morphology, physiology, growth, development, reproduction or life span of an organism, system or (sub) population that results in an impairment of functional capacity, an impairment of the capacity to compensate for additional stress or an increase in susceptibility to other influences "(IPCS / WHO, 2009)
(2) it has an endocrine mode of action;
(3) there is a plausible link between the observed adverse effect and the endocrine mode of action.
This change in wording would make the Commission proposal were in line with the WHO / IPCS definition, which has been used by the Commission as a basis for setting the scientific criteria for ED Substances.
With respect to Section A 2., on how to identify endocrine disrupting properties, we have the following observations:
• We agree on the wording of sub-paragraph (1) but in (1a) "and" appearing before "mechanistic studies" should go before "in vitro"
• In paragraph 2. (3) (b), change "Adverse effects or endocrine modes of action" by "adverse effects related to endocrine modes of action"
Madrid, 22nd July 2016