What are they?

A carcinogenic or cancer-causing substance is one that can cause cancer or increase its incidence. Exposure may occur, among other routes, through inhalation, ingestion or skin contact.

Cancer comprises a broad range of diseases characterised by uncontrolled growth and division of certain cells. Some cancer cells can invade nearby tissues and spread to other parts of the body.

The time between exposure to a carcinogenic agent and the onset of the disease can be very long. Therefore, the relationship between occupational exposure and cancer may not be evident, and the disease may appear years after exposure has ended

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Mutagens are substances or mixtures that can cause mutations, i.e. permanent changes in the genetic material of a cell. Some agents can cause genetic alterations in germ cells and may therefore have consequences for offspring.

Carcinogenic and mutagenic agents form part of the so-called CMR agents, together with agents toxic to reproduction. The Royal Decree 665/1997, in its current wording, regulates protection against carcinogenic, mutagenic or reprotoxic agents at work.

How are they identified?

The Regulation (EC) No 1272/2008 (CLP) classifies the hazards of substances and mixtures and establishes the corresponding hazard statements.

For carcinogenic agents:

1. Carc. 1A: known carcinogen to humans.
2. Carc. 1B: presumed carcinogen to humans.
3. Carc. 2: suspected carcinogen to humans.

The main hazard statements are:

1. H350: May cause cancer.
2. H350i: May cause cancer by inhalation.
3. H351: Suspected of causing cancer.

For mutagenic agents in germ cells:

1. Muta. 1A: substance known to induce heritable mutations in human germ cells.
2. Muta. 1B: substance considered to induce heritable mutations in human germ cells.
3. Muta. 2: substance suspected of inducing heritable mutations in human germ cells.

The main hazard statements are:

1. H340: May cause genetic defects.
2. H341: Suspected of causing genetic defects.

The official classification and applicable criteria can be found in Annex I of Regulation (EC) No 1272/2008 (CLP).

What should be done?

Occupational exposure to carcinogenic and mutagenic agents must be avoided or reduced to the minimum possible level.

The legislation establishes a hierarchy of preventive measures, giving priority to the elimination and substitution of the hazardous agent. When substitution is not technically possible, measures must be applied to prevent or reduce exposure, prioritising collective protection measures and control of exposure at source.

Among other measures, the following should be considered:

1. Avoid using the agent whenever possible.
2. Substitute it with a substance, mixture, procedure or process that is not hazardous or is less hazardous.
3. Use closed systems whenever technically possible.
4. Prevent or minimise the release of the agent in the workplace.
5. Limit the number of workers who are or may be exposed.
6. Design work procedures that reduce exposure.
7. Use appropriate extraction and ventilation systems.
8. Apply appropriate hygiene and cleaning measures.
9. Use personal protective equipment when necessary.
10. Delimit and signpost risk areas.
11. Prevent eating, drinking or smoking in areas where there is a risk of exposure.
12. Keep work or protective clothing adequately separated from ordinary clothing.
13. Ensure the cleaning and decontamination of work clothing and prevent workers from taking it home.
14. Provide suitable facilities for personal hygiene.

Royal Decree 665/1997 establishes specific obligations for employers where there is or may be exposure to carcinogenic, mutagenic or reprotoxic agents.

Substitution

Substitution should be the first preventive option whenever technically possible. The aim is to eliminate the hazardous agent from the process or replace it with another agent presenting a lower risk.

Occupational exposure limit values should not, on their own, be interpreted as a guarantee that there is no risk. Their function and significance must be interpreted in accordance with the specific legislation and the characteristics of the agent.

In the case of reprotoxic agents identified by Royal Decree 665/1997 as having no threshold, the legislation itself establishes that there is no safe level of exposure for workers' health.

Carcinogenic, mutagenic and reprotoxic agents (CMR)

Since the amendment introduced by Royal Decree 612/2024, Royal Decree 665/1997 protects against the following agents:

1. Carcinogenic agents, which can cause cancer.
2. Mutagenic agents, which can cause genetic alterations.
3. Reprotoxic agents, which can affect sexual function and fertility or the development of offspring.

For the purposes of Royal Decree 665/1997, carcinogenic, mutagenic or reprotoxic agents include, among others, substances or mixtures that meet the criteria for classification as carcinogenic, germ cell mutagenic or toxic to reproduction in categories 1A or 1B under the CLP Regulation.

Specific information on effects on fertility, pregnancy, development and breastfeeding should also be consulted in the risks to reproduction, pregnancy and breastfeeding section of RISCTOX.

Pregnancy, breastfeeding and reproductive health

The prevention of risks arising from CMR agents must take into account possible effects on fertility, pregnancy, development and breastfeeding.

Risk assessment must take into account the characteristics and circumstances of exposed workers and adopt the necessary preventive measures.

Royal Decree 665/1997 also establishes specific obligations to report cases of cancer and certain adverse effects on sexual function, fertility and development that are recognised as occupational contingencies and are related to exposure to carcinogenic, mutagenic or reprotoxic agents.

Where known differences in toxicity or exposure according to sex exist, these must be taken into account in the risk assessment. It should not be assumed that all workers have the same susceptibility or the same exposure conditions.

IARC classification

The International Agency for Research on Cancer (IARC), a specialised agency of the World Health Organization, evaluates agents, mixtures and circumstances of exposure on the basis of the available scientific evidence regarding their carcinogenicity to humans.

The classification currently used by IARC comprises:

The IARC classification expresses the strength of the evidence concerning the carcinogenic hazard and does not, by itself, establish the risk associated with a particular occupational exposure.

The absence of an agent from the IARC lists does not mean that it has been demonstrated to be harmless or that it cannot cause cancer.

Consult: IARC, Agents Classified by the IARC Monographs. The current list includes evaluations from volumes 1–142.

Other sources of information

In addition to the classification under the CLP Regulation and IARC evaluations, there are other official sources that can provide toxicological and preventive information.

These include:

1. ECHA (European Chemicals Agency): harmonised classification and labelling, information on substances and the REACH Regulation.
2. INSST (National Institute for Occupational Safety and Health, Spain): information and technical documentation on occupational risk prevention.
3. NTP (National Toxicology Program, United States): toxicological information and assessments.
4. OSHA (Occupational Safety and Health Administration, United States): information on occupational risks and prevention.
5. California Proposition 65: official list of substances recognised by the State of California as causing cancer, birth defects or other reproductive harm.

These classifications and lists have different criteria, purposes and fields of application and should not be considered equivalent to the legal classification established by the CLP Regulation.

Legislation

1. Law 31/1995, of 8 November, on Occupational Risk Prevention.
2. Regulation (EC) No 1272/2008 (CLP), on the classification, labelling and packaging of substances and mixtures, and its amendments in force.
3. Royal Decree 665/1997, of 12 May, on the protection of workers against risks related to exposure to carcinogenic, mutagenic or reprotoxic agents at work, in its current wording.
4. Royal Decree 374/2001, of 6 April, on the protection of the health and safety of workers against risks related to chemical agents at work.
5. Royal Decree 39/1997, of 17 January, approving the Regulation on Prevention Services.
6. Regulation (EC) No 1907/2006 (REACH), concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals.

The consolidated text of Royal Decree 665/1997 currently records the amendment made by Royal Decree 612/2024, of 2 July as the latest published amendment.

Directive (EU) 2024/869

Directive (EU) 2024/869, of 13 March 2024, amends Directives 2004/37/EC and 98/24/EC with regard to occupational exposure limit values for lead and its inorganic compounds and for diisocyanates. The Directive is in force and established 9 April 2026 as the deadline for its transposition.

Guidance and reference publications

INSST

Technical Guide for the assessment and prevention of risks related to exposure to carcinogenic or mutagenic agents at work. INSST, 2022.

This is the specific INSST technical guide for the application of Royal Decree 665/1997 concerning carcinogenic and mutagenic agents.

Technical Guide for the assessment and prevention of risks related to chemical agents present in workplaces. INSST, 2022.

It complements the information on the assessment and prevention of occupational chemical risks.

IARC

IARC Monographs on the Identification of Carcinogenic Hazards to Humans.

An international reference source for the assessment of scientific evidence on carcinogenicity. The list of classified agents is updated periodically.

References

Last updated: August 2026