How can chemicals cause harm?

How can chemicals cause harm? Let me count the ways.

This compendium identifies the regulatory hazard classes and miscellaneous hazards identified in chemicals legislation. It includes all the GHS categories, plus additional hazards noted in other legal texts, and as emerging hazards.

Hazard communication, through safety data sheets (SDSs) and labelling, depends on hazard classification – a shorthand description for the hazards that a chemical product can pose to human health and the environment. The GHS is a worldwide classification system, comprising 29 hazard classes into 100 sub-categories.

For more information on the GHS hazard classification, see here.

I have also listed common hazards that are not (yet!) subject to hazard classification. Most hazard communication legislation has a requirement that such hazards that have been identified are included as part of the safety data sheet. See the guide on the contents of the SDS.

The hazard classification system is based on pragmatic considerations, rather than any grand theory, so there are overlaps and anomalies. It can be divided into physical, toxicological and ecological hazards.

Physico-chemical hazards

Physico-chemical hazards mainly relate to fire and explosion. The hazard classes range from substances which spontaneously combust on exposure to air (pyrophoric substances) to those that produce heat slowly if stored in large quantities for long periods (self-heating substances).

The most common hazard class is for flammable liquids.

Oxidising substances may not be themselves be flammable, but accelerate the combustion of other materials. Peroxides are a type of oxidising substance.

The advent of the GHS in 2003, and its adoption in the EU in 2008 as the CLP Regulation, aligned physico-chemical hazard criteria with the UN Recommendations on the Transport of Dangerous Goods.

Toxicological hazards

Chemical hazard classification does not provide detailed toxicology that might be required for the evaluation of medicines. Instead there are broad hazard classes that can be understood with a few general principles.

Acute (short-term) toxicity relates to effect from a single, large dose of substance. If adverse effects occur at a low dose, the substance is highly toxic.

Repeated-dose (long-term) toxicity is relevant for worker exposure, where exposure is lower than the acute case, but repeated over longer periods. The hazard class for this is called ‘specific target organ toxicity – repeated exposure’ (STOT-RE).

Local effects are those produced where contact with the chemical occurs, particularly in skin or eye irritation. Often the hazard pertains to a type of chemical, for example acids or surfactants, rather than a specific substance.

Systemic effects occur after the chemical has been absorbed into the bloodstream and distributed around the organism. In this way adverse effects can be produced in organs distant from the initial exposure, eg via dermal absorption or inhalation.

Respiratory (eg asthma) and skin sensitisation (eg dermatitis) requires repeated exposure to cause sensitisation. Thereafter, allergic reaction can be produced from only small exposures. Fragrance ingredients have frequently been sensitisers, and have been more tightly controlled in recent years in cosmetic and other consumer products.

Some substances can alter the structure of DNA, giving mutated cells. In exposed organisms, this can result in serious adverse effects of carcinogenicity (tumour formation) or genetic defects passed on to offspring (germ-cell mutagenicity). Such substances, along with others causing reproductive or developmental effects by other mechanisms, are sometimes collectively called CMRs (carcinogens, mutagens, and toxics for reproduction), and are substances of very high concern (SVHC) in the EU and UK REACH legislation.

Ecological hazards

Ecological hazards are an increasingly important part of the regulatory landscape.

Hazard classification is based on effects in aquatic organisms at three levels of the food-chain: algae, Daphnia (water fleas), and fish.

Classification is assigned based on short-term (acute), high-dose effects that might occur in a spill, and long-term (chronic) effects that are more realistic for regular contamination from an industrial process.

Chemicals breakdown in the environment as a result of bacterial action in a process of biodegradation. Biodegradation also contributes to environmental hazard classification. Substances that biodegrade rapidly in the environment have a less severe chronic hazard classification.

Conversely, substances that persist in the environment are potentially more hazardous, and have received much attention from regulatory authorities.

Persistent substances that bioaccumulate or toxic are designated as substances of very high concern (SVHC), and subject to restriction and authorisation under the REACH Regulation.

Regulatory authorities are focussing on persistent substances that are mobile in the aquatic environment, and pose a threat to natural water systems. This comes after much media and public pressure concerning perfluoroalkyl and polyfluoroalkyl substances (PFAS).

Bioaccumulating chemicals have also seen strong regulatory action. Human and wildlife concentrate such chemicals in their bodies when they are exposed to lower levels from their environment. While bioaccumulation is not strictly part of the classification system, the EU has developed criteria and procedures for designating and controlling such chemicals.

Hazards not covered by the classification systems

The classification system covers most hazards and is fit for purpose of hazard communication.
Some hazard classes, particularly STOT-RE, cover a wide variety of effects but may be too general to capture some neurological of behavioural effects.

Endocrine effects may be captured by STOT-RE or reproductive and developmental toxicity, but there is increasing recognition that a separate hazard class is necessary.

The development of nanomaterials has been a challenge for regulators, as there is the possibility of increased physico-chemical and toxicological hazard from very small particles compared to the usual forms.

Persistent chemicals have caused significant environmental contamination that is implicated in adverse effects in wildlife. There is no hazard classification for terrestrial wildlife or plant toxicity. Endocrine effects in wildlife from environmental contaminants are poorly understood.

Classifications listing for EU and UK CLP Regulation, with notes for UN GHS

Physico-chemical hazards

CLP and GHS reference	Hazard Class	Hazard Categories and notes
Section 2.1	Explosives	Unstable explosive; Divisions 1.1 to 1.6
Section 2.2	Flammable gases	Cat 1A, 1B and 2. Cat 1A includes flammable gases, pyrophoric gases and chemical unstable gases; Cat 1B includes flammable gases, and chemically unstable gases.
Section 2.3	Aerosols	Cat 1, 2 and 3 (EU and UK do not include GHS chemicals under pressure, Cat 1, 2, and 3)
Section 2.4	Oxidizing gases	Cat 1
Section 2.5	Gases under pressure	Compressed gas, liquefied gas, refrigerated liquefied gas, dissolved gas
Section 2.6	Flammable liquids	Cat 1, 2, and 3 (EU and UK do not include GHS Cat 4)
Section 2.7	Flammable solids	Cat 1 and 2
Section 2.8	Self-reactive substances and mixtures	Types A, B, C, D, E, F and G
Section 2.9	Pyrophoric liquids	Cat 1
Section 2.10	Pyrophoric solids	Cat 1
Section 2.11	Self-heating substances and mixtures	Cat 1 and 2
Section 2.12	Substances and mixtures which, in contact with water, emit flammable gases	Cat 1, 2 and 3
Section 2.13	Oxidizing liquids	Cat 1, 2 and 3
Section 2.14	Oxidizing solids	Cat 1, 2 and 3
Section 2.15	Organic peroxides	Types A, B, C, D, E, F and G
Section 2.16	Corrosive to metals	Cat 1
Section 2.17	Desensitised explosives	Cat 1, 2, 3 and 4

Toxicological hazards

CLP and GHS reference	Hazard Class	Hazard Categories and notes
Section 3.1	Acute toxicity (oral, dermal, inhalation – gases, vapours, dust/mist)	Cat 1, 2, 3 and 4 (EU and UK do not include GHS Cat 5)
Section 3.2	Skin corrosion/irritation	Cat 1, 1A, 1B, 1C and 2. Cat 1 used where sub-characterisation into Cat 1A, 1B, or 1C not possible. (EU and UK do not include GHS Cat 3)
Section 3.3	Serious eye damage/eye irritation	Cat 1 and 2 (EU and UK do not use GHS sub-categories Cat 2A and 2b)
Section 3.4	Respiratory or skin sensitisation	Both Cat 1, 1A, 1B. Cat 1 used where sub-characterisation into Cat 1A, 1B not possible.
Section 3.5	Germ cell mutagenicity	Cat 1A, 1B and 2
Section 3.6	Carcinogenicity	Cat 1A, 1B and 2
Section 3.7	Reproductive toxicity	Cat 1A, 1B and 2 (+ effects on or via lactation)
Section 3.8	Specific target organ toxicity – single exposure (STOT-SE)	Cat 1, 2 and 3 (Cat 3 narcotic effects and respiratory tract irritation)
Section 3.9	Specific target organ toxicity – repeated exposure (STOT-RE)	Cat 1 and 2
Section 3.10	Aspiration hazard	Cat 1 (EU and UK do not include GHS Cat 2)

Ecological hazards

CLP and GHS reference	Hazard Class	Hazard Categories and notes
Section 4.1	Hazardous to the aquatic environment	Cat Acute 1; Cat Chronic 1, 2, 3 and 4 (EU and UK do not include GHS Cat Acute 2 and 3)
Section 5.1	Hazardous to the ozone layer	Hazardous to the ozone layer, Cat 1

Supplemental chemical hazards identified in the EU and UK

The following chemical hazards have been identified in the CLP Regulation (Article 25 and Annex II) for the EU and UK, and should be communicated in the supply chain in the SDS and on the label. These phrases are not part of the UN, EU or UK classification system, but are regarded as supplementary information. The are identified by the EUH coding.

Hazard Code	Hazard phrase
EUH014	Reacts violently with water
EUH018	In use, may form flammable/explosive vapour–air mixture
EUH019	May form explosive peroxides
EUH029	Contact with water liberates toxic gas
EUH031	Contact with acids liberates toxic gas
EUH032	Contact with acids liberates very toxic gas
EUH044	Risk of explosion if heated under confinement
EUH066	Repeated exposure may cause skin dryness or cracking
EUH070	Toxic by eye contact
EUH071	Corrosive to the respiratory tract

Other chemical hazards recognised in EU legislation as ‘substances of very high concern’

EU and UK REACH aim to identify and substitute substances of very high concern (SVHCs) identified in REACH Article 57. SVHCs are included in a candidate list and require authorisation before use. SVHCs include carcinogens, mutagens, and reproductive toxicants, which are defined in the CLP hazard classification system. Below are other hazard types that are not included in the classification system, but considered to be SVHCs.

Hazard	Description and notes
Endocrine disruptor	A substance that causes adverse effects in organisms via interference with its hormonal system. The effect occurs in humans and wildlife. There is a legal definition, but as yet no set criteria for testing and classification.
PBT	Persistent, bioaccumulative and toxic substance, according to REACH Annex XIII criteria. These are persistent pollutants that accumulate in humans and wildlife, particularly in their fatty tissues, causing adverse effects. It may be impossible to avoid exposure to such substances as they distribute widely in the environment.
vPvB	Very persistent and very bioaccumulative substances, according to REACH Annex XIII criteria. These are persistent pollutants that accumulate in humans and wildlife, particularly fatty tissues, causing a body burden of the substance often with unknown long-term effects. It may be impossible to avoid exposure to such substances as they can distribute widely in the environment.

Other chemical hazards recognized in legislation in the USA

US hazard classification legislation (HazCom 2012) recognises additional hazards, not covered in the classification system, as show below.

Hazard	Description and notes
Combustible dust	May form combustible dust concentrations in air. Finely divided solid particles of a substance or mixture that are liable to catch fire or explode on ignition when dispersed in air or other oxidizing media [GHS, and part of US HazCom 2012 classification system].
Simple asphyxiant	May displace oxygen and cause rapid suffocation. A substance or mixture that displaces oxygen in the ambient atmosphere, and can thus cause oxygen deprivation in those who are exposed, leading to unconsciousness and death.

Emerging hazards

These hazards are attracting regulatory attention and may become part of hazard evaluation and classification.

Hazard	Description and notes
Mixtures	Normal mixtures are a standard part of hazard classification. However, there is concern over the combination effects of chemicals. Even if each chemical is below the threshold for causing harm, there is potential adverse effects for humans and wildlife exposed to a ‘cocktail of chemicals’ via the environment. Endocrine disrupters are of particular concern for combination effects. Related to this is synergistic effects, where combined exposure of substances causes effects more severe that would be predicted from a simple additive effect. The irritation or corrosive effects of a substance can magnified if a surfactant is also present. STOT-RE hazard may also show synergistic effects from combined exposures.
Nanomaterials	Nanomaterials are a form of substance supplied in very fine particles and have far higher surface area than conventional materials. These properties may alter the physico-chemical reactivity, and absorption by organisms. As of 1 January 2020, REACH requires explicit legal reporting for nanomaterials in the SDS.
PMT	Persistent, mobile and toxic. An emerging hazard in the EU, that may become recognised as a ‘substance of very high concern‘ (SVHC) according to Article 57 of REACH. Water solubility may make such substances a hazard to remote aquatic environments and sources of drinking water. May include perfluoroalkyl and polyfluoroalkyl substances (PFAS).
vPvM	Very persistent, very mobile. An emerging hazard in the EU, that may become recognised as a ‘substance of very high concern’ (SVHC) according to Article 57 of REACH. Water solubility may make such substances a hazard to remote aquatic environments and sources of drinking water. A hazard to remote aquatic environments and sources of drinking water. May include perfluoroalkyl and polyfluoroalkyl substances (PFAS).

Hazards not part of chemical hazard classification

The UN GHS hazard classification system does not cover all chemical hazards. Some hazards are too specialised for general chemicals, but are important in other regulatory schemes, such as for plant protection products, biocides, or cosmetics.

Hazard	Description and notes
Global warming potential	Greenhouse gases warm the atmosphere by absorbing energy. Their hazard relates to their ability to absorb energy (radiative efficiency), and their persistence in the atmosphere (half-life). Halogenated hydrocarbons such as chlorofluorocarbons (CFCs) and perfluorocarbons (PFCs), and sulfur hexafluoride (SF6) have global warming potentials thousands of times higher than carbon dioxide.
Photo-irritation and photo-sensitisation	Some chemicals only exert adverse effects, such as irritation or sensitisation after irradiation with UV light. Such effects are important for UV absorbers in cosmetic products.
Toxicity to terrestrial organisms	Toxicity to terrestrial plants is not part of the hazard classification system. Toxicity testing for effects on terrestrial and soil and sediment dwelling organisms is only required by the REACH Regulation when the chemical is supplied at high tonnages. Such testing depends on the outcome of the chemical safety assessment. Such testing is required in biocide and plant protection product authorisation, along with specialised testing for beneficial insects and wildlife, which might include endocrine effects.
Toxicity to terrestrial plants	Direct toxicity to terrestrial plants is not part of the hazard classification system. Acid rain has been a problem, and is caused by the dissolving of acidic gases, particularly nitrogen oxides and sulphur dioxide, causing harm to forests either directly or through soil effects.