Alternative to formaldehyde in fluid preservation of biological specimens.

Number

092-EN

Section

General Section

Use

Sector

Scientific research and development

Function

Embalming agent

Process

Treatment of articles by dipping and pouring
Manual activities involving hand contact

Product category

laboratory chemicals

Application

Preserving biological specimen for pharmaceutical and cosmetic industry

Abstract

22 alternatives were assessed as alternatives to formaldehyde in preserving biological specimens. DMDM-hydantoin was regarded as a suitable alternative. DMDM-hydantoin is also used in pharmaceutical and cosmetic products.

Substituted substances

Formaldehyde

CAS No. 50-00-0 EC No. 200-001-8 Index No. 605-001-00-5

Chemical group

Aldehyde

Classification: hazard statements

H350 May cause cancer
H341 Suspected of causing genetic defects
H331 Toxic if inhaled
H311 Toxic in contact with skin
H301 Toxic if swallowed
H314 Causes severe skin burns and eye damage
H317 May cause an allergic skin reaction

Other adverse effects

The substance is: 1 carcinogen (IARC) as listed in the Substance Database according to SUBSPORT Screening Criteria (SDSC).

Ethanol

CAS No. 64-17-5 EC No. 200-578-6 Index No. 603-002-00-5

Chemical group

Alcohol

Classification: hazard statements

H225 Highly flammable liquid and vapour

Other adverse effects

The substance is: 1 carcinogen (IARC), as listed in the Substance Database according to SUBSPORT Screening Criteria (SDSC).

Alternative Substances

DMDM hydantoin

CAS No. 6440-58-0 EC No. 229-222-8 Index No.

Chemical group

Lactams; urea derivatives

Reliability of information

Internet information: data are from an internet document and only a basic and partial evaluation could be performed

Reason substitution

CMR
skin/respiratory sensitizing

Hazard Assessment

Substances to be substituted: Formaldehyde and Ethanol are in the database of hazardous substances according to SUBSPORTplus criteria. Formaldehyde is a sensitiser, may cause cancer, is toxic if swallowed, is toxic in contact with skin, causes severe skin burns and eye damage, is toxic if inhaled and is suspected of causing genetic defects. Ethanol is flammable and a group 1 carcinogen (IARC), as listed in the Substance Database according to SUBSPORTplus Screening Criteria (SDSC). Alternative substance: The proposed alternative DMDM-hydantoin is not classified and is not in the database of hazardous substances according to SUBSPORTplus criteria. It is a formaldehyde releasing substance allowed in pharmaceutical and cosmetic products.

Description of Substitution

Despite that new antiseptic mixtures are introduced in the pharmaceutical and cosmetic industry every year fluid preservation of biological specimens is still based on formaldehyde and ethanol. Ethanol is highly flammable and formaldehyde is recognised as a highly toxic substance. The aim of the study was to determine the suitability of biocides used in the pharmaceutical and cosmetic industry to preserve biological specimens. The biocide was assessed according to six parameters: antiseptic range, water/fat solubility coefficient, pH range, stability/reactivity, toxicity and flammability. A biocide out of range of the present parameters was not considered to be a suitable alternative. First the substances were assessed according to the technical parameters. The substances that passed these were assessed according to the safety parameters. 22 substances were reviewed according to this process: ethanol, isopropanol, formaldehyde, glutaraldehyde, sodium benzoate, methylparaben, ethylparaben, propylparaben, butylparaben, chlorhexidine, triclosan, triclocarban, hexachlorophene, DMDM-hydantoin, chloroxylenol, silver nitrate, bronopol, phenol, phenoxetol, sodium propionate, benzalkonium chloride, potassium sorbate. Only DMDM-hydantoin was considered to be a suitable alternative, although DMDM-hydantoin is a formaldehyde-releasing agent. A 55% solution contains 2% released free formaldehyde and 17-18.5 % bound formaldehyde. Only the free formaldehyde is volatile. In products such as shampoos and skin lotions it is regarded as safe in concentration of 1%. Ethanol passed all technical parameters but was discarded because of the flammability. The study concludes, that most biocides used in food, cosmetic and pharmaceutical products are not considered to be suitable for preservation of biological specimens. DMDM-hydantoin passes all 6 parameters. DMDM-hydantoin has never been used for this purpose and therefore its long term effect on the integrity of the specimens is not known.

Case/substitution evaluation

Most of the 22 evaluated alternatives were not technical suitable. Ethanol is a group 1 carcinogen (IARC), as listed in the Substance Database according to SUBSPORTplus Screening Criteria (SDSC). Formaldehyde is classified both concerning carcinogenic and sensitising effect and therefore DMDM-hydantoin is a better alternative. This case study shows a successful substitution of sensitizing and carcinogenic substances with an alternative which has no harmonised classification according to Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation). However, formulators must be careful to limit the concentration of free formaldehyde, as this is a 2A carcinogen (IARC), 1A or 1B carcinogen (CLP Regulation), a sensitiser (H317, H334; CLP Regulation) as listed in the Substance Database according to SUBSPORT Screening Criteria (SDSC).

State of implementation

Pilot study

Availability of Alternative

Alternative is available on the market.

Type of information supplier

Research

Type of publication and availability

Only abstract freely available

Publication source: author, company, institute, year

Dam, Andries. (2003). DMDM-Hydantoin: The Promising Result of a Search for an Alternative in Fluid Preservation of Biological Specimens. Collection Forum. 18. 104-115.

Publication source

Type of publication and availability

https://www.researchgate.net/publication/242369545_DMDM-Hydantoin_The_Promising_Result_of_a_Search_for_an_Alternativ

Date, reviewed

December 11, 2020