Result card

  • SAF12: How can one increase safety of professionals applying uPA/PAI-1, Oncotype DX or MammaPrint® (including technology-, user-, and patient-dependent aspects)?

How can one increase safety of professionals applying uPA/PAI-1, Oncotype DX or MammaPrint® (including technology-, user-, and patient-dependent aspects)?

Authors: Iris Pasternack, Emilio Chiarolla, Narine Sahakyan, Leonor Varela

Internal reviewers: Pseudo100 Pseudo100, Pseudo163 Pseudo163, Pseudo169 Pseudo169, Pseudo219 Pseudo219, Pseudo90 Pseudo90, Pseudo94 Pseudo94

A search was done by IP on 21 February 2012 in PubMed. Search strategy

  • 23 Add Search (#22) AND #21 35
  • 22 Add Search hospital[Title/Abstract] 550947
  • 21 Add Search (#20) AND #17 1505
  • 20 Add Search (#19) OR #18 546515
  • 19 Add Search work[Title/Abstract] 483270
  • 18 Add Search occupational[Title/Abstract] 79830
  • 17 Add Search (#16) OR #15 39041 04:41:15
  • 16 Add Search formaldehyde[Title/Abstract] 14641
  • 15 Add Search formalin[Title/Abstract] 24748

The search yielded 35 articles {Appendix SAF-3}. The National Toxicology Program Final Report on Carcinogens 2010 was taken as the basis for carcinogenicity information. As there are sufficient EU sources for safety epidemiology and safety management, all guidelines prepared for the non-European context were excluded.

Information was also retrieved from web pages of manufacturers, the EU-OSHA, the draft NICE report 2012, the European Commission Joint Research Centre’s European Chemical Substances Information System (ESIS), and the WHO IPCS. As there is no free database for MSDS, the best way to find the data sheets is to Google MSDS and formaldehyde.

T = Any tissue sample requiring formalin fixation

I = Staff in surgical theatres and pathological laboratories

C = Procedures by which formalin is eliminated or substituted

O = Cancers, respiratory symptoms

The concentrations of formaldehyde and its metabolite in blood or urine have proven to be inefficient measures of exposure (13). Occupational exposure limits (OELs) are the major control instruments for workers’ exposure assessment and management. There are two types of OELs: atmospheric and biological, and two main legal levels: constraining (binding) and indicative. More information about national exposure limits and monitoring regulation, as well as possible statutory health surveillance can be found through the national Focal Points of the European Agency for Safety and Health at Work, which are official government-nominated representatives of EU-OSHA (

Minimum requirements for the protection of workers from risks to their safety and health arising, or likely to arise, from the effects of chemical agents that are present at the workplace or as a result of any work activity involving chemical agents are presented in Directive 98/24/EC—risks related to chemical agents at work (

EU regulations* define the preventive measures at work places:

  • assess the risk
  • eliminate or substitute the agent
  • prevent exposure
  • inform and train workers
  • monitor exposure and health problems
  • record the findings
  • consult workers or their representatives

see details in OSHA Factsheet

  • Council Directive 98/24/EC of 7 April 1998 on the protection of the health and safety of workers from the risks related to chemical agents at work and
  • Directive 2000/54/EC of the European Parliament and of the Council of 18 September 2000 on the protection of workers from risks related to exposure to biological agents at work.

Checklist for laboratory accidents

Eliminating exposure:

Several attempts have been made to find a substitute for formalin in hospitals and laboratories but all alternatives have failed (23). Another approach has been to change the work flow so that no formalin is needed in the surgical theatre and the samples are transported to the pathological laboratory for formalin fixation. This would reduce exposure to formaldehyde in the surgical theatre where advanced preventive and exposure limiting solutions, such as hoovers, are missing. A system using cooling and pressure-vacuum sealing of the fresh tissue sample in the surgical theatre before moving it to the pathology laboratory for formalin fixation has been used in a hospital in Turin. According to one before–after study, the quality of tissue conservation improved and the odds of having respiratory symptoms in surgical staff who used formalin fixation in the theatre was 12 times as large as that among staff who use the vacuum sealing method (24, 25).

Preventing exposure:

Several countries have their own standards for limiting exposure to formalin and monitoring procedures. The Industrial Health Foundation experts’ panel identified in 1997 an OEL that would prevent irritation. The panel concluded that for most people, eye irritation that is clearly due to formaldehyde does not occur below at least 1.0 ppm. Information from controlled studies involving volunteers indicated that moderate to severe eye, nose, and throat irritation does not occur for most people until airborne concentrations exceed 2.0–3.0 ppm. The data indicated that below 1.0 ppm, if irritation occurs in some people, the effects rapidly subside due to "accommodation." Based on the weight of evidence from published studies, the panel found that those exposed to 0.3 ppm for 4–6 h in chamber studies generally reported eye irritation at a rate no different than that observed when people were exposed to clean air. It was noted that at a concentration of 0.5 ppm (8-h time-weighted average [TWA]) eye irritation was not observed in the majority of workers (about 80%) (21).

Formalin spills are not that rare and they require attention. Material safety data sheets present protocols for avoiding spills. They should be stated in the laboratory’s standard operating procedures. The amount of formaldehyde gas that evaporates depends on the surface area, not the volume spilled, so the aim should be to minimise the surface area of the spill. Cleaning should therefore start immediately. A dike made of wet paper can be used to prevent the surface area of the formalin from increasing. A spill kit should be reserved, with disposable gowns, gloves, and safety glasses. Goggles and a wet mask should be worn while cleaning up. The wet mask should be changed often while it gets saturated with formalin. Ventilation should be increased and water taps left running to increase the humidity in the room. For irritation of the throat, milk or alkaline drinks are optimal for immediate drinking and gargling. Eye washing for some minutes with cold water after formalin splashing is obligatory and every histology laboratory must have an eyewash fountain.

Checklist for laboratory accidents

Pasternack I et al. Result Card SAF12 In: Pasternack I et al. Safety In: Jefferson T, Vicari N, Raatz H [eds.]. Prognostic tests for breast cancer recurrence (uPA/PAI-1 [FEMTELLE], MammaPrint, Oncotype DX ) [Core HTA], Agenzia nationale per i servizi sanitari regionali (, Italy ; 2013. [cited 3 December 2022]. Available from: