Our project proposes the replacement of Formalin with GAF, a non-toxic and non-cancerogenic fixative solution, with equivalent (if not better) histological efficacy, responding to the need to protect the health of workers involved and, at the same time, the health of patients.
Furthermore, the project is aimed at protecting the environment by reducing the use and disposal of a toxic product such as Formaldehyde. In fact, Formaldehyde’s carcinogenic and toxic vapours absorbed by the hoods are partially released into air, while the disposal of liquid Formalin is complex and expensive. It is desirable that the amount of toxic waste released in the environment, although somehow controlled, be strongly reduced.
Therefore, the replacement of Formalin is recommended for both environmental and health reasons. Furthermore, they are now normatively mandated by EU legislation. Glyoxal (a di-aldehyde similar to Formaldehyde) is not volatile nor toxic. When deprived of troublesome acids, Glyoxal Acid-Free (GAF) represents a safe histological fixative and a Formalin alternative, providing results as good (or even better) than Formalin. This has been proved by histological, immuno-histochemical and molecular analyses.
Tissue fixation, leading to preservation of structural components by fixation and permeabilization of cells and tissues, plays a critical role in histopathological diagnosis.
The fixative of choice is still represented by Formalin (a water solution of Formaldehyde).
This reagent is toxic and cancerogenic, but is still used worldwide in the lack of alternative fixative solutions guaranteeing similar results.
GAF (Glyoxal, acid free) fixative solution is an innovative reagent that allows optimal tissue fixation at the structural and molecular level, combined with the absence of toxicity and carcinogenic activity.
The validation of GAF fixative, as compared to Formalin, was conducted on parallel samples, obtained with core needles or punch devices from surgical specimens and fixed alternatively in Formalin and in GAF.
The first Validation trial was conducted in December 2017 at the San Giovanni Battista Hospital of Turin.
Validation of GAF fixative, as compared to Formalin, is conducted through national and international Trials evaluating results of parallel samples, obtained from surgical specimens, fixed alternatively in Formalin and in GAF. The first Validation trial was conducted at the San Giovanni Battista Hospital of Turin, Italy. The results confirmed the feasibility and validity of GAF fixation as alternative to Formalin fixation.
Representative slides (10 cases in parallel, fixed either in Formalin or in GAF) of this first Trial are shown below.
In recent years, the high toxicity and carcinogenicity of Formaldehyde has been increasingly recognized worldwide from both a scientific and regulatory point of view. The numerous examples of this recognition, and the following normative restriction on the use of Formaldehyde, include: in the United States (at the federal level) – the Formaldehyde Emission Standards for Composite Wood Products, the Toxic Substances Control Act, the Resource Conservation and Recovery Act, the Clean Water Act, and the Clean Air Act; in Canada – the Canadian Environmental Protection Act, and the Hazardous Products Act; in Brazil – the Resolução nº 37 of 03/06/2008. Value limits to airborne concentration of Formaldehyde were also introduced, inter alia, in China and Japan. In the European Union, Directive 2004/37/EC, Regulation 2006/1907/EC and Regulation 2008/1272/EC recognized Formaldehyde as a carcinogenic substance and prohibited its use, production and commercialization from August 2017. More recently, the European Parliament Resolution of 27 March 2019 recommended the Member States to minimize exposure to Formaldehyde, and the EU Directive 983/2019 stressed Formaldehyde’s classification as a carcinogenic substance, and recognized its nature as a contact allergen for the skin. The abovementioned EU normative system do envisage a system of authorization to produce and commerce Formaldehyde, where absolutely necessary. EU Directive 983/2019 recognized that, on the basis of this system of authorization, and due to its high degree of diagnostic accuracy, Formaldehyde is still routinely used in the healthcare sector across the Union. Indeed – at present, and not considering GAF – there is no valid (i.e. accepted by the scientific community) alternative to Formaldehyde to preserve cell or tissue specimen. For the health sector, Directive 983/2019 also introduced a transitional period of five years during which the allowed limit value of Formaldehyde in the workplace (airborne concentration) is increased. However, it should be stressed that normatively (at least in the EU) there is still a legal obligation on both the public sector and Formaldehyde manufacturers, importers and users to seek for alternatives (e.g. Regulation 1907/2006, Article 55, “all manufacturers, importers and downstream users applying for authorizations shall analyze the availability of alternatives and consider their risks, and the technical and economic feasibility of substitution.”) From a legal point of view, we are currently in a “transitional arrangement” phase, in which the use of Formaldehyde is tolerated, and subject to derogative authorization, only by virtue of the absence of valid substitutes. Formaldehyde is used in the impossibility of a primary prevention: i.e. the elimination of risks with the use of different substances. As a consequence, in particular in the healthcare system, thousands of workers (e.g. nurses, technicians, doctors, pathologists) are still exposed to Formaldehyde. Until now, the balancing point between the diagnostic (i.e. patient’s health) and the worker’s protection interests is based on the reduction of risks according to the principle of “As Low As Reasonably Achievable”. The risk deriving from exposure must be reduced by implementing an efficient technical, organizational and procedural framework (chemical fume cupboards, safety procedures, etc.). As a consequence, the use of Formaldehyde brings a consistent economic and legal burden for the employer and/or involved occupational physicians. Indeed, the number of lawsuits for employer’s liability concerning work-related diseases connected to the use of Formaldehyde is increasing (see, for instance, in the United States: the so-called “Lumber Liquidators Scandal” and the lawsuit filed against the FDA by Women’s Voices and the Environmental Working Group).
ADDAX Biosciences was born as a spin off of the University of Turin, which contribuited with support to the research activity.
Our company has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No 8157692.
The project “GAF – Towards a hospital without formalin” is realized thanks to the co-financing of POR FESR Piemonte 2014-2020, Ob.1 – “Research, technological development and innovation, I.1.b.4.1 “Support for creation and consolidation of innovative start-ups with a high intensity of application and knowledge and research spin-off initiatives”.
The project aims to validate, produce and market GAF, a histological fixative without carcinogenicity, that works as a substitute to Formalin. Achieving the project’s objectives will improve the working conditions of health and research professionals, protecting them from the risk of developing occupational diseases caused by inhaling Formalin vapours.