What are they?

Neurotoxic substances are chemicals capable of producing adverse effects on the nervous system. These effects may affect the central nervous system (CNS), the peripheral nervous system (PNS) and the sense organs.

Neurotoxicity comprises functional, structural or biochemical alterations of the nervous system that may manifest themselves through different adverse effects. These may include alterations in sensory and motor functions, changes in memory and learning, behavioural changes, impaired coordination, paraesthesia, neuropathies and other neurological disorders. Some effects may be transient, while others may persist after exposure has ceased.

The manifestation of neurotoxic effects depends, among other factors, on the properties of the substance, the dose and duration of exposure, the route of entry and the individual characteristics of the people exposed. The INSST's NTP 487 also points out that differences in response may be related to individual factors, including age and sex.

Not all substances that produce effects on the nervous system are necessarily legally classified as “neurotoxic”. Neurotoxicity is a toxicological concept and does not, in itself, constitute an independent hazard class under Regulation (EC) No 1272/2008 (CLP).

Hazard identification

Regulation (EC) No 1272/2008 (CLP) establishes the hazard classes and categories to be used for the classification of substances and mixtures. There is no general category called “neurotoxic” under the CLP Regulation.

Certain substances that produce effects on the nervous system may be classified under the hazard class specific target organ toxicity (STOT).

The relevant hazard statements may include:

1. H336: May cause drowsiness or dizziness. This statement corresponds to certain narcotic effects within specific target organ toxicity following a single exposure (STOT SE, Category 3).
2. H370: Causes damage to organs.
3. H371: May cause damage to organs.
4. H372: Causes damage to organs through prolonged or repeated exposure.
5. H373: May cause damage to organs through prolonged or repeated exposure.

Where the affected organ is the nervous system, this information should be checked in the substance's classification and, where applicable, in the safety data sheet.

The text of the CLP Regulation can be consulted here:

Regulation (EC) No 1272/2008 (CLP) – EUR-Lex

What should be done?

Exposure to substances with neurotoxic potential should be subject to preventive risk assessment whenever they may be present in the workplace.

Royal Decree 374/2001 on the protection of the health and safety of workers against risks related to chemical agents at work establishes the minimum provisions for protection against risks arising from the presence of hazardous chemical agents in the workplace. Its scope covers hazardous chemical agents that are or may be present at work.

Prevention must follow the general principles of preventive action established in Law 31/1995 on Occupational Risk Prevention. Risk assessment must take into account the hazardous properties of the agent, the conditions of exposure and the characteristics of the work.

Where there is a risk of exposure to neurotoxic substances, priority should be given to:

1. Eliminating the hazardous substance or process, where possible.
2. Replacing the substance with a less hazardous one, whenever technically feasible and appropriate.
3. Applying technical and collective protection measures to reduce the generation and dispersion of the contaminant and prevent or reduce exposure.
4. Adopting organisational and hygiene measures to reduce the number of people exposed, as well as the intensity and duration of exposure.
5. Using personal protective equipment where the measures described above are not sufficient or while other preventive measures are being implemented.

Risk assessment should take into account the different routes of exposure and, where appropriate, the possibility of effects resulting from prolonged or repeated exposure.

The INSST provides a technical guide specifically addressing the assessment and prevention of risks related to chemical agents present in the workplace:

Technical Guide for the Assessment and Prevention of Risks Related to Chemical Agents Present in the Workplace – INSST, 2022

Guidance

1. Technical Guide for the Assessment and Prevention of Risks Related to Chemical Agents Present in the Workplace – INSST, 2022
2. NTP 487: Neurotoxicity: Neurotoxic Agents – INSST .

Classification

There is no single regulatory model for classifying all neurotoxic substances.

Regulation (EC) No 1272/2008 (CLP) does not establish an independent hazard class called “neurotoxicity”. Neurotoxic effects may primarily fall under specific target organ toxicity (STOT) when the nervous system is one of the affected organs.

The CLP distinguishes between:

1. STOT SE — Specific target organ toxicity, single exposure: covers non-lethal toxic effects occurring following a single exposure to a substance or mixture. It may include functional alterations of the central or peripheral nervous system, whether reversible or irreversible, immediate or delayed.
2. Within this class, Category 3 (STOT SE 3) covers only certain transient effects, specifically narcotic effects and respiratory tract irritation. In the case of narcotic effects, the corresponding hazard statement is H336: “May cause drowsiness or dizziness.”
3. STOT RE — Specific target organ toxicity, repeated exposure: covers toxic effects occurring following repeated exposure to a substance or mixture. Where the available evidence indicates that the nervous system is the target organ, the classification may include a statement such as H372: “Causes damage to organs through prolonged or repeated exposure” or H373: “May cause damage to organs through prolonged or repeated exposure”, indicating the affected organ where appropriate.

The Regulation itself states that the principal target organ of toxicity should be identified where possible and expressly refers, among other examples, to neurotoxic substances.

The classification of a substance as STOT SE or STOT RE must be carried out in accordance with the criteria and evidence established in the CLP Regulation. The presence of a specific hazard statement does not, on its own, make it possible to identify all possible forms of neurotoxicity.

Acute toxicity should not be considered a category of neurotoxicity. Acute poisoning may cause severe neurological effects, but the acute toxicity categories under the CLP constitute an independent hazard class. Therefore, hazard statements H300, H301, H310, H311, H330 and H331 should not, on their own, be used to identify neurotoxic substances.

Similarly, carcinogenicity, mutagenicity and reproductive toxicity (CMR) are independent hazard classes. A substance may simultaneously present neurotoxicity and one of these hazards — for example, where there are effects on nervous system development — but CMR categories do not constitute a classification of neurotoxicity.

Therefore, two concepts should be distinguished when identifying the substances:

1. Neurotoxicity as a toxicological property, which may be established on the basis of experimental, epidemiological or other evidence.
2. Legal hazard classification under the CLP, which may reflect certain neurotoxic effects mainly through the STOT SE and STOT RE categories when their criteria are met.

Regulation (EC) No 1272/2008 (CLP) – EUR-Lex

Legislation

1. Law 31/1995 of 8 November on Occupational Risk Prevention – BOE
2. 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 – BOE
3. Regulation (EC) No 1272/2008 (CLP) on the classification, labelling and packaging of substances and mixtures – EUR-Lex

References

1. INSST. Technical Guide for the Assessment and Prevention of Risks Related to Chemical Agents Present in the Workplace. 2022.
2. INSST. NTP 487: Neurotoxicity: Neurotoxic Agents. 1998.

Last uptade August 2026