Number

012-EN

Section

General Section

Use

Abstract

Formaldehyde is an organic compound used as a tissue fixative for microscopy and histology. Formaldehyde was substituted by a product containing: ethyl alcohol, isopropyl alcohol and acetic acid under the commercial name Fixall-his.

Substituted substances

Alternative Substances

Reliability of information

Evidence of implementation: there is evidence that the solution was implemented and in use at time of publication

Reason substitution

CMR
skin/respiratory sensitizing

Hazard Assessment

Formaldehyde is a carcinogen cat. 1 according to IARC and 1B to CLP (H350). It is also a sensitizer: may cause sensitization by skin contact (H317). Because of these two important risks, formaldehyde is listed in the hazardous Substance Database according to SUBSPORT Screening Criteria (SDSC). Alternative Substances: Ethanol substance is 1 carcinogen (IARC), as listed in the Substance Database according to SUBSPORT Screening Criteria (SDSC). However, this applies to alcoholic beverages. Propan-2-ol and Acetic acid meet the SUBSPORT criteria.

Description of Substitution

Introduction A significant volume of highly toxic formaldehyde wastes was detected during the development of a plan for the reduction of healthcare wastes with the participation of the trade union (CC.OO.). Formaldehyde is classified as carcinogen by IARC and CLP. The heads of the regional trade union’s environmental and health and safety departments (Aragon) commissioned ISTAS to carry out a study on the viability of substituting formaldehyde by a less toxic chemical. Researchers sought alternatives to formaldehyde for the preservation and preparation of tissue samples in pathology labs of healthcare centers. Eventually the compound named Fixall-his was chosen for substitution. Fixall-his is the commercial name of a product containing: ethyl alcohol, isopropyl alcohol and acetic acid. The compound was chosen for its relatively low level of health risks and the successful experience of substitution in French hospitals. The fact that substitution had already occurred in other hospitals is a significant driver in convincing social players of its validity as a substitute of Formaldehyde as a fixative of tissue samples. Description of procedure or technology (including pre-/post-processing) Way of application: e.g. spraying, dipping, open/closed system etc. Risk management measures (technical, organizational and personal) Risk reduction by alternative: Human health: e.g. more/less safety measures e.g. technical/operational/personal protection measures Hat keinen unangenehmen Geruch. The alternative does not have an unpleasant smell. Risk reduction by alternative: Environment: e.g. waste reduced/increased Reduction of a significant volume of highly toxic formaldehyde waste.

Case/substitution evaluation

Comments The alternative contains isopropanol which vapors may cause drowsiness and dizziness besides being irritating to eyes. However the original substance has much higher risks as formaldehyde is a sensitizer and a carcinogenic for human beings. The alternative is safer, but it should be handle with care, with proper ventilation and respiratory protection. Advantage or Disadvantage of alternative

Aspect	Advantage/disadvantage to conventional process
Technical requirements	Weniger toxisch für den Anwender.
Implementation	Disadvantages Certain problems were found in immunohistochemical detections. No bio-molecular tests have been conducted. The mix is distributed in tanks of fluorinated polyethylene. The mix is classified as highly flammable (H225).
Operational expenses
etc.

State of implementation

In use

Date and place of implementation

France

Enterprise using the alternative

www.ch-avignon.fr

">http://www.ch-avignon.fr">www.ch-avignon.fr

Producer/Provider

www.carloerbaragents.com

">https://www.carloerbareagents.com/en/">www.carloerbaragents.com

Type of information supplier

Producer / distributor

Other solutions

The conclusions of a ISTAS's study on the alternatives are summarized below. There is no universal method of fixation. Fixatives adequate for certain types of tissues might not be suitable for others. Besides, not all fixative compounds preserve tissues indefinitely. Alternatives include:
Physical methods of tissue fixation
- Freezing
- Freeze drying (cryodesiccation) or lyophilization
- Cryosubstitution

During the transfer of samples to laboratories formaldehyde can be substituted by a vacuum packing equipment which can also be used for processing big samples.

Methods of chemical fixation

- Acetone
- Acetic Acid
- Sulfosalicylic acid
- Glutaraldehyde
- Osmium tetraoxide
- Ionic liquids (ILs).

- 1-methyl-3 octyloximethylimidazolium tetrafluoroborate, which achieve the best results.

- Tissues fixed with alcohol-based non-crosslinking fixatives (RCL2)

The intrinsic risks of chemical alternatives compounds were assessed.

Further information

Fixative FIXALL-HIS liquid RS https://www.carloerbareagents.com/en/catalog/product/view/id/424623/category/28637

MSDS">https://www.carloerbareagents.com/en/catalog/product/view/id/424623/category/28637">https://www.carloerbareagents.com/en/catalog/product/view/id/424623/category/28637

MSDS https://www.carloerbareagents.com/en/msds/search/index/q/FIXALL

">https://www.carloerbareagents.com/en/msds/search/index/q/FIXALL">https://www.carloerbareagents.com/en/msds/search/index/q/FIXALL

Date, reviewed

February 9, 2022