Strengthening the classification of diphenylguanidine used to manufacture rubber
La diphénylguanidine est une substance utilisée principalement dans la fabrication du caoutchouc. Suite à son évaluation, l’Anses propose de renforcer sa classification au niveau européen pour mieux protéger la santé humaine contre les troubles neurologiques et les atteintes à la fertilité et au développement en particulier. Cette proposition de classification dans le cadre du règlement CLP (classification, étiquetage et emballage) est en consultation publique depuis le 18 mars sur le site de l’agence européenne des produits chimiques (ECHA), afin que toutes les parties prenantes puissent commenter ou apporter les informations complémentaires dont elles disposent sur cette substance.
A substance used as an intermediate in the manufacture of rubber
Diphenylguanidine (DPG) is a synthesis intermediate used mainly as a vulcanisation accelerator in the manufacture of rubber, making it more resistant to pressure and stress. Residues of this substance can be found in rubber articles such as floor coverings, footwear, toys and tyres. It has also been detected in drinking water and household dust. Its presence has been reported in the aquatic environment and seems to be associated with particles released due to tyre wear.
Strengthened classifications to protect human health
Diphenylguanidine currently has a harmonised classification at European level under the CLP Regulation. During the process to assess DPG under the REACH Regulation, ANSES concluded that this harmonised classification needed to be revised. In particular, the Agency determined that the level of evidence concerning the substance's reprotoxic nature justified an increase in its classification, following an updated assessment of the substance's various effects in light of the latest available data.
The Agency is therefore proposing changes to the classifications for human health, particularly regarding acute effects on the skin and eyes, as well as on reproduction and development. In several studies, DPG has been shown to be toxic by ingestion and corrosive to the eyes of rodents. In addition, numerous human studies have revealed cases of allergy to DPG. Most of these data are from retrospective studies carried out in the workplace that investigated sensitisation to DPG in patients with a suspected allergy to rubber gloves. Lastly, studies have shown the effects of DPG on fertility and development in rats and mice, as well as neurological disorders in rats.
"Classification as a Category 1B reprotoxic substance will have direct repercussions on the protection of worker health because of the obligations to implement reinforced preventive measures for carcinogenic, mutagenic and reprotoxic substances set out in the French Labour Code," explains Alice Mateus, who assessed DPG. ANSES is also continuing its work on the substance as part of an analysis of the best regulatory management option (RMOA). It aims to verify the need for additional regulatory measures, taking a strengthened classification into account.
Lastly, with regard to its environmental effects, ANSES is proposing a less stringent classification. Based on the most recent and reliable biodegradation study, DPG is considered to be rapidly biodegradable, with a low bioaccumulation potential. Studies show chronic toxicity for aquatic organisms, with algae being the most sensitive species tested.
For all these reasons, ANSES is recommending that DPG be classified and labelled as follows under the CLP Regulation:
Acute toxicity (ingestion); Category 3 (H301: Toxic if swallowed). ANSES has proposed using the value of 110 mg/kg as the Acute Toxicity Estimate (ATE) for the classification of mixtures, based on a study in rats;
Skin irritation; Category 2 (H315: Causes skin irritation);
Serious eye damage; Category 1 (H318: Causes serious eye damage);
Skin sensitisation; Category 1A (H317: May cause an allergic skin reaction);
Reproductive toxicity; Category 1B (H360FD: May damage fertility. Suspected of damaging the unborn child);
Specific target organ toxicity (repeated exposure); Category 2 (H373: May cause damage to the central nervous system through prolonged or repeated exposure);
Hazardous to the aquatic environment; chronic toxicity Category 3 (H412: Harmful to aquatic life with long lasting effects).
Classification proposal submitted for public consultation
The harmonised classification proposal for DPG was submitted for public consultation on the ECHA website on 18 March 2024 for a period of two months. The aim of this consultation is to give all stakeholders the opportunity to comment on these proposals, by providing any additional scientific arguments and information they may have. Comments can be sent via a dedicated form on the ECHA website.
Following this consultation stage, ANSES will be asked to respond to the comments received. The initial proposal, comments and ANSES's responses to them will be submitted for analysis to ECHA’s Committee for Risk Assessment, which will then issue its opinion on updating the classification of DPG.
Based on this opinion, the European Commission will draft regulatory texts allowing the proposed classification to be included in the CLP Regulation.
The Regulation on Classification, Labelling and Packaging (CLP)
Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures, known as the CLP Regulation, is the legislation in force in the European Union to ensure the protection of workers, consumers and the environment with regard to chemicals. In particular, it aims to identify any hazards posed by a substance or substance mixture due to its physico-chemical properties and its effects on health and the environment.
This Regulation defines how these substances and mixtures must be classified, labelled and packaged. It also has an impact on other European regulations able to translate hazard characteristics into stricter requirements, which may go as far as prohibition decisions or substitution obligations.
Once a substance or mixture has been classified with regard to the identified hazards, appropriate labelling informs the user about these hazards through pictograms and safety data sheets. ECHA is responsible for implementing the CLP Regulation.