What are they?

Reproductive toxicants or reproductive toxic agents are substances or mixtures that may cause adverse effects on the sexual function and fertility of adult men and women, as well as on the development of offspring.

Reproductive toxicity may affect sexual function and fertility, the production and transport of reproductive cells, the normal development of the reproductive cycle and pregnancy outcomes. It may also cause adverse effects on the development of offspring before or after birth.

Effects on reproduction do not only concern pregnancy. A substance may impair fertility in men and women, affect offspring as a result of exposures occurring before conception, or cause effects during prenatal or postnatal development.

Regulation (EC) No 1272/2008 (CLP) distinguishes between:

1. Adverse effects on sexual function and fertility.
2. Adverse effects on the development of offspring.
3. Effects on or via lactation.

For classification purposes, effects on or via lactation are considered a separate hazard category.

Hazard statements

The main hazard statements related to reproductive toxicity are:

H360: May damage fertility or the unborn child.

This statement may be specified according to the effect identified:

1. H360F: May damage fertility.
2. H360D: May damage the unborn child.
3. H360FD: May damage fertility. May damage the unborn child.
4. H360Fd: May damage fertility. Suspected of damaging the unborn child.
5. H360Df: May damage the unborn child. Suspected of damaging fertility.

For substances classified in Category 2:

H361: Suspected of damaging fertility or the unborn child.

Depending on the effect identified, the following may be used:

1. H361f: Suspected of damaging fertility.
2. H361d: Suspected of damaging the unborn child.
3. H361fd: Suspected of damaging fertility. Suspected of damaging the unborn child.

For effects on or via lactation:

H362: May cause harm to breast-fed children.

It is important to distinguish between hazard classification and occupational risk prevention. The CLP Regulation establishes how the hazard of a substance or mixture is classified and communicated. Occupational health and safety legislation establishes the obligations and measures that must be applied when there is exposure at work.

Since July 2024, Royal Decree 665/1997 expressly includes reproductive toxicants in Categories 1A and 1B within its scope of application. For the purposes of this Royal Decree, a reproductive toxicant is a substance or mixture that meets the classification criteria for reproductive toxicity Category 1A or 1B established in Annex I to the CLP Regulation.

What should be done?

Exposure to reproductive toxicants must be avoided or reduced by applying the principles of preventive action.

When dealing with reproductive toxicants falling within the scope of Royal Decree 665/1997, the specific measures established by this legislation must be applied.

Substitute the reproductive toxicant

Substitution is the first preventive measure. Whenever technically possible, the company must avoid using the reproductive toxicant by replacing it with a substance, mixture or process that is not hazardous or is less hazardous to health and safety.

Use a closed system

When substitution is not technically possible, the production and use of the agent must take place in a closed system.

Reduce exposure

When it is also not technically possible to use a closed system:

1. For reproductive toxicants without a threshold, exposure must be reduced to a level as low as technically possible.
2. For reproductive toxicants with a threshold, the risk must be reduced to a minimum.
3. For reproductive toxicants that have not been identified as having or not having a threshold, the risk assessment must consider the possibility that there is no safe level of exposure and appropriate measures must be adopted.

Exposure must also not exceed the limit values established in the Annex III of Royal Decree 665/1997. Not exceeding a limit value does not exempt the company from applying the other preventive measures.

Technical and organisational measures

When reproductive toxicants are used, the company must implement the necessary measures to:

1. Limit the quantities present in the workplace.
2. Design processes to avoid or minimise the formation of reproductive toxicants.
3. Limit to the lowest possible number the people exposed or liable to be exposed.
4. Extract the agents at source by local exhaust ventilation or, where this is not technically possible, by adequate general ventilation.
5. Use appropriate measurement methods, particularly to detect abnormal exposures.
6. Apply appropriate work procedures and methods.
7. Give priority to collective protective measures and use personal protective measures when exposure cannot be avoided by other means.
8. Maintain appropriate hygiene conditions.
9. Delimit and signpost risk areas and restrict access to them.
10. Keep containers, packaging and installations containing these agents properly labelled.
11. Have warning systems for emergency situations that could result in abnormally high exposures.
12. Ensure the safe storage, handling and transport of the agents, as well as the safe management of waste.

Hygiene and protective equipment

Where there is a risk of contamination by reproductive toxicants, the company must adopt appropriate hygiene and protective measures.

These include prohibiting eating, drinking or smoking in work areas where there is a risk of contamination, using appropriate protective clothing, and keeping work or protective clothing separate from personal clothing. The company must be responsible for washing and decontaminating work clothing, and such clothing must not be taken home for washing.

Personal protective equipment must be used when exposure cannot be avoided by other means and as a complement to collective protective measures.

Risk assessment

Where there is exposure or a possibility of exposure to reproductive toxicants, the risk assessment must determine the nature, degree and duration of exposure.

All routes of entry into the body must be taken into account, including absorption through the skin, as well as the characteristics of the activities, possible accidental exposures and people who may be particularly sensitive to certain risks.

Information and training

The company must ensure that people who work and their representatives receive sufficient and appropriate information and training on the risks and preventive measures.

The information must include, among other aspects:

1. Potential health risks.
2. Precautions to prevent exposure.
3. Hygiene measures.
4. The use of protective equipment and clothing.
5. Measures to be taken in the event of an incident and to prevent incidents.

Training must be updated when knowledge develops, new risks arise or working conditions change.

Health surveillance

The company must ensure appropriate and specific health surveillance of people who work in relation to exposure to carcinogenic, mutagenic or reproductive toxic agents, carried out by competent healthcare professionals.

Health surveillance must be offered:

1. Before exposure begins.
2. At regular intervals, taking into account the agent, type of exposure and available medical knowledge.
3. When a health alteration is detected that may be related to exposure.
4. When a biological limit value has been exceeded, in the cases provided for by legislation.

Where a biological limit value is established in the Annex III bis to Royal Decree 665/1997, health surveillance is mandatory in accordance with the conditions established in that Annex.

Pregnancy and lactation

The prevention of risks during pregnancy and lactation must be integrated into the risk assessment.

Law 31/1995 establishes that the assessment must determine the nature, degree and duration of exposure of pregnant workers or workers who have recently given birth to agents, procedures or working conditions that may have a negative effect on their health or that of the foetus. The same law establishes specific measures where there is a risk to pregnancy or lactation.

The risk assessment must also take into account factors that may affect the reproductive function of people who work, including those arising from exposure to chemical agents that may cause effects on fertility or on the development of offspring.

Where there is a specific risk to pregnancy or lactation, the preventive measures provided for by legislation must be applied, beginning with adapting working conditions or working time and, where this is not possible, changing the person to a compatible job or function under the terms established by law.

Protection during pregnancy and lactation does not replace the general obligation to prevent exposure of all people who work to reproductive toxicants.

Guidance

1. Reproductive Toxicants. INSST, 2025. Specific leaflet on the identification, risks and preventive measures relating to these agents.
2. Technical Guide for the Assessment and Prevention of Risks Related to Chemical Agents Present in the Workplace. INSST, 2022. Non-binding technical guide associated with Royal Decree 374/2001.
3. Technical Guide for the Assessment and Prevention of Risks Related to Occupational Exposure to Carcinogenic or Mutagenic Agents. INSST, 2022. It may be used as a technical reference for the provisions of Royal Decree 665/1997 that are applicable, bearing in mind that this edition was published before reproductive toxicants were expressly included in 2024.
4. Occupational Exposure Limits for Chemical Agents in Spain 2026. INSST. Provides the occupational exposure limit values adopted for 2026 and updates the INSST OEL application.
5. Substitution Support Sheets: Substitution as the Most Effective Measure. INSST, 2025. Collection intended to facilitate and promote the substitution of carcinogenic, mutagenic or reproductive toxic agents.

Classification

The CLP Regulation establishes the hazard class reproductive toxicity and distinguishes effects on sexual function and fertility, effects on development, and effects on or via lactation.

Category 1A

Substances known to be toxic to human reproduction.

Classification is based primarily on evidence from human studies.

Signal word: Danger.

Hazard statement: H360, specified according to the known effect.

Category 1B

Substances presumed to be toxic to human reproduction.

Classification is based primarily on data from animal studies providing sufficient evidence to consider an effect on human reproduction likely.

Signal word: Danger.

Hazard statement: H360, specified according to the identified effect.

Substances or mixtures classified as reproductive toxicants in Category 1A or 1B fall within the scope of Royal Decree 665/1997.

Category 2

Substances suspected of being toxic to human reproduction.

There is evidence from human or animal studies indicating possible adverse effects on sexual function, fertility or development, but the evidence is not sufficiently convincing to classify them in Categories 1A or 1B.

Signal word: Warning.

Hazard statement: H361, specified according to the identified effect.

Substances classified exclusively as Category 2 reproductive toxicants are not included, on the basis of that classification, in the definition of a reproductive toxic agent under Royal Decree 665/1997. However, they remain hazardous chemical agents and their exposure must be assessed and prevented in accordance with the applicable legislation.

Effects on or via lactation

Effects on or via lactation constitute an additional and separate hazard category.

H362: May cause harm to breast-fed children.

This classification is made independently of whether a substance is also classified as a Category 1A, 1B or 2 reproductive toxicant.

H362 must not be confused with H373. H373 refers to specific target organ toxicity following prolonged or repeated exposure and is not the hazard statement for effects on or via lactation.

Reproductive toxicants with and without a threshold

Royal Decree 665/1997 distinguishes between:

1. Reproductive toxicant without a threshold: an agent for which there is no safe level of exposure for the health of people who work and which is identified as such in the remarks column of Annex III.
2. Reproductive toxicant with a threshold: an agent for which there is a safe level of exposure below which there are no health risks for people who work and which is identified as such in the remarks column of Annex III.

This distinction is relevant when determining exposure reduction measures where substitution and the use of a closed system are not possible.

Legislation

1. Law 31/1995, of 8 November, on Occupational Risk Prevention, particularly Articles 15, 16 and 26, on the principles of preventive action, risk assessment and protection during pregnancy and lactation. The consolidated text published by the BOE was updated on 9 April 2026.
2. Royal Decree 665/1997, of 12 May, on the protection of people who work against risks related to exposure to carcinogenic, mutagenic or reproductive toxic agents at work, in its current wording.
3. Royal Decree 612/2024, of 2 July, amending Royal Decree 665/1997 and expressly including reproductive toxicants within its scope of application.
4. Regulation (EC) No 1272/2008 (CLP), on the classification, labelling and packaging of substances and mixtures, particularly Annex I, Section 3.7, on reproductive toxicity.
5. Royal Decree 374/2001, of 6 April, on the protection of the health and safety of people who work against risks related to chemical agents at work. The INSST maintains its associated technical guide in the 2022 edition.
6. Royal Decree 39/1997, of 17 January, approving the Regulation on Prevention Services, including provisions relating to risk assessment and protection during pregnancy and lactation.
7. Royal Decree 298/2009, of 6 March, amending Royal Decree 39/1997 in relation to measures to promote improvements in the safety and health at work of pregnant workers, workers who have recently given birth or workers who are breastfeeding.
8. Directive (EU) 2022/431, of 9 March 2022, amending Directive 2004/37/EC to include reproductive toxicants in the European framework for protection against occupational exposure. It was transposed into Spanish law through Royal Decree 612/2024.

References

The main official sources used to update this section are:

Last content update: August 2026