Reproductive toxicity

Reproductive toxicity means that any of the following apply to the industrial chemical: 

• the chemical is known, presumed or suspected to produce adverse effects on sexual function and fertility, as described in chapter 3.7 of the GHS, with the chemical classified as toxic to reproduction (category 1 or 2), or 
• the chemical is on the list of chemicals with high hazards for categorisation based on its reproductive toxicity, or 
• the chemical is an ester or salt of specified chemicals in the table below, which are on the list of chemicals with high hazards for categorisation based on reproductive toxicity, unless an exception as identified in the table below is met for that chemical, or 
• an in vivo study on the chemical conducted following an acceptable test guideline for reproductive toxicity, carcinogenicity, chronic toxicity, subchronic oral toxicity, subchronic dermal toxicity or subchronic inhalation toxicity results in adverse effects on sexual function and fertility, as described in chapter 3.7 of the GHS.

Information required to demonstrate the absence of the hazard characteristic, reproductive toxicity  

• If the chemical is a polyhalogenated organic chemical and the human health exposure band for the introduction is 4 - 
  • an in vivo test result on the chemical or suitable read across information conducted following an acceptable test guideline for reproductive toxicity, which results in none of the adverse effects on sexual function or fertility described in chapter 3.7 of the GHS;
• Otherwise – 
  • confirmation that the chemical is not on the list of chemicals with high hazards for categorisation, based on its reproductive toxicity
  • confirmation that the chemical is not an ester or salt of the specified chemicals shown in the below table, which are on the list of chemicals with high hazards for categorisation based on reproductive toxicity.

Reproductive toxicity - exception criteria

Check the following table - an ester or salt of the chemical has the reproductive toxicity hazard characteristic, unless one or more of the following exception criteria apply. 
 

Note – Low levels of low molecular weight species (in relation to a polymer) means less than 10% (by mass) of molecules with a molecular weight that is less than 500 g/mol and less than 25% (by mass) of molecules with a molecular weight that is less than 1,000 g/mol.

Developmental toxicity

Developmental toxicity means that any of the following apply to the industrial chemical:

• the chemical is known, presumed or suspected to produce adverse effects on the development of the offspring or effects on the offspring via lactation, as described in chapter 3.7 of the GHS, with the chemical classified as follows: 
  • toxic to reproduction (category 1 or 2), or 
  • effects on or via lactation, or 
• the chemical is on the list of chemicals with high hazards for categorisation based on its developmental toxicity, or
• the chemical is an ester or salt of specified chemicals in the table below, which are on the list of chemicals with high hazards for categorisation based on developmental toxicity, unless an exception as identified in the table below is met for that chemical, or 
• an in vivo study on the chemical conducted following an acceptable test guideline for developmental toxicity or reproductive toxicity results in adverse effects on the development of the offspring or effects on the offspring via lactation, as described in chapter 3.7 of the GHS.
   

Information required to demonstrate the absence of the hazard characteristic, developmental toxicity

• If the chemical is a polyhalogenated organic chemical and the human health exposure band for the introduction is 4 – 
  • an in vivo test result on the chemical or suitable read across information conducted following an acceptable test guideline for developmental toxicity or reproductive toxicity which results in none of the adverse effects on the development of the offspring or effects on the offspring via lactation, as described in chapter 3.7 of the GHS
• Otherwise – 
  • confirmation that the chemical is not on the list of chemicals with high hazards for categorisation, based on its developmental toxicity and
  • confirmation that the chemical is not an ester or salt of the specified chemicals shown in the below table, which are on the list of chemicals with high hazards for categorisation, based on developmental toxicity.

Developmental toxicity - exception criteria

Check the following table - an ester or salt of the chemical has the development toxicity hazard characteristic, unless one or more of the following exception criteria apply. 

Note – Low levels of low molecular weight species (in relation to a polymer) means less than 10% (by mass) of molecules with a molecular weight that is less than 500 g/mol and less than 25% (by mass) of molecules with a molecular weight that is less than 1,000 g/mol
  

Adverse effects mediated by an endocrine mode of action

Adverse effects of mediated by an endocrine mode of action means that any of the following apply to the industrial chemical: 

• the chemical meets all of the following: 
  • it shows an adverse effect in an intact organism or its progeny, which is a change in the morphology, physiology, growth, development, reproduction or lifespan of an organism, system or (sub)population that results in an impairment of functional capacity, an impairment of the capacity to compensate for additional stress or an increase in the susceptibility to other influences, and 
  • it has an endocrine activity, which is the capacity to alter the function(s) of the endocrine system, and 
  • the adverse effect is a consequence of the endocrine activity

or

• the chemical is on the list of chemicals with high hazards for categorisation, based on its adverse effects mediated by an endocrine mode of action or 
• the chemical is an ester or salt of specified chemicals in the table below, which are on the list of chemicals with high hazards for categorisation based on adverse effects mediated by an endocrine mode of action unless an exception, as identified in the table below, is met for that chemical, or 
• the chemical meets all of the following: 
  • information is available that is relevant to determining whether the chemical has the hazard characteristic, adverse effects mediated by an endocrine mode of action, and 
  • the information has been considered in a weight of evidence analysis based on the following guidance documents: 
    • the EU guidance for identifying endocrine disruptors*, and 
    • the guidance provided in OECD GD 150**; and 
  • the weight of evidence analysis concludes that the chemical has the hazard characteristic, adverse effects mediated by an endocrine mode of action. 

Information required to demonstrate the absence of the hazard characteristic, adverse effects mediated by an endocrine mode of action

• If the chemical has existing information relevant to determining whether it has the hazard characteristic, adverse effects mediated by an endocrine mode of action, information is required to demonstrate that the chemical does not have this hazard characteristic: 
  • this must involve a documented weight of evidence analysis based on the EU guidance for identifying endocrine disruptors* and the guidance in OECD GD 150**, and 
  • the analysis must conclude that the chemical does not have the hazard characteristic, adverse effects mediated by an endocrine mode of action.
• Otherwise– 
  • confirmation that the chemical is not on the list of chemicals with high hazards for categorisation, based on its adverse effects mediated by an endocrine mode of action and
  • confirmation that the chemical is not an ester or salt of the specified chemicals shown in the below table, which are on the list of chemicals with high hazards for categorisation, based on adverse effects mediated by an endocrine mode of action. 

Adverse effects mediated by an endocrine mode of action - exception criteria

Check the following table - an ester or salt of the chemical has the adverse effects mediated by an endocrine mode of action hazard characteristic, unless one or more of the following exception criteria apply. 

Note – Low levels of low molecular weight species (in relation to a polymer) means less than 10% (by mass) of molecules with a molecular weight that is less than 500 g/mol and less than 25% (by mass) of molecules with a molecular weight that is less than 1,000 g/mol.

*Guidance for the identification of endocrine disruptors in the context of 39 Regulations (EU) No 528/2012 and (EC) No 1107/2009, 2018 

**‘OECD Series on Testing and Assessment, No. 150 - Revised Guidance Document 150 on Standardised Test Guidelines for Evaluating Chemicals for Endocrine Disruption.’  OECD, OECD Series on Testing and Assessment, No. 150, 2018
 

Genetic toxicity

Genetic toxicity means that any of the following apply to the industrial chemical: 

• the chemical is known to induce or may induce mutations in the germ cells of humans, as described in chapter 3.5 of the GHS, with the chemical classified as germ cell mutagenicity (category 1 or 2), or 
• the chemical is on the list of chemicals with high hazards for categorisation, based on its genetic toxicity, or 
• the chemical is an ester or salt of specified chemicals in the table below, which are on the list of chemicals with high hazards for categorisation based on genetic toxicity unless an exception, as identified in the table below, is met for that chemical, or 
• an in vitro study on the chemical:
  • conducted following an acceptable test guideline for gene mutation or chromosomal abnormalities results in the prediction of mutagenic or genotoxic effects, as described in chapter 3.5 of the GHS, and 
  • the results of the study have not been negated by in vivo studies conducted on the chemical for gene mutation, chromosomal abnormalities or heritable germ cell mutagenicity, or 
• an in vivo study on the chemical conducted following an acceptable test guideline for gene mutation, chromosomal abnormalities or heritable germ cell mutagenicity results in mutagenic or genotoxic effects, as described by chapter 3.5 of the GHS.

Information required to demonstrate the absence of the hazard characteristic, genetic toxicity

The information required to demonstrate that a chemical does not have the hazard characteristic, genetic toxicity, is: 

• if the human health exposure band for the introduction is 4 - at least one of the following: 
  • information to demonstrate that the chemical is included on the Select Committee on GRAS Substances (SCOGS) Database as a Type 1 conclusion, and that the human health exposure expected from the industrial use of the chemical is no higher than the human health exposure expected from food use, or 
  • information to demonstrate that the chemical has been notified to the US FDA GRAS notification program and FDA had no questions about the notifier’s conclusion of GRAS status, and that the human health exposure expected from the industrial use of the chemical is no higher than the human health exposure expected from food use, or 
  • information that demonstrates that the chemical is a substance covered by Entry 9 of Annex V of the REACH Regulation, or 
  • information to demonstrate that the chemical is a high molecular weight polymer, and if you are seeking to demonstrate that the introduction meets the criteria for very low risk and is not one of the 'special cases' mentioned in step 4.5 - test results from an in vitro study on the polymer or from suitable read across information conducted following an acceptable test guideline for gene mutation, which demonstrates the absence of mutagenic effects, or 
  • test results that demonstrate the absence of mutagenic or genotoxic effects from both: 
    • study on the chemical or from suitable read across information conducted following an acceptable test guideline for gene mutation, and 
    • study on the chemical or from suitable read across information conducted following an acceptable test guideline for chromosomal abnormalities. 
• if the human health exposure band for the introduction is 3, and you are seeking to demonstrate that the introduction meets the criteria for very low risk and is not one of the 'special cases' mentioned in step 4.5 - at least one of the following: 
  • inclusion of the chemical in the Select Committee on GRAS Substances (SCOGS) Database as a Type 1 conclusion, as long as the human health exposure expected from the industrial use of the chemical is no higher than the human health exposure expected from food use, or 
  • the chemical has been notified to the US FDA GRAS notification program and FDA had no questions about the notifier’s conclusion of GRAS status, as long as the human health exposure expected from the industrial use of the chemical is no higher than the human health exposure expected from food use, or 
  • information that demonstrates that the chemical is a substance covered by Entry 9 of Annex V of the REACH Regulation, or
  • if the polymer is a high molecular weight polymer, test results from an in vitro study on the polymer or from suitable read across information conducted following an acceptable test guideline for gene mutations, which demonstrates the absence of mutagenic effects, or 
  • information that demonstrates the absence of mutagenic or genotoxic effects from both: 
    • information on the chemical or from suitable read across information that addresses gene mutations - this could be: 
      • a suitable in silico prediction, both with and without metabolic activation, or 
      • test results from a study conducted following an acceptable test guideline for gene mutations; and
    • test results from a study on the chemical or from suitable read across information conducted following an acceptable test guideline for chromosomal abnormalities.
• Otherwise– 
  • confirmation that the chemical is not on the list of chemicals with high hazards for categorisation, based on its genetic toxicity and
  • confirmation that the chemical is not an ester or salt of the specified chemicals shown in the below table, which are on the list of chemicals with high hazards for categorisation, based on genetic toxicity.

Note – Low levels of low molecular weight species (in relation to a polymer) means less than 10% (by mass) of molecules with a molecular weight that is less than 500 g/mol and less than 25% (by mass) of molecules with a molecular weight that is less than 1,000 g/mol. 

Genetic toxicity - exception criteria

Check the following table - an ester or salt of the chemical has the genetic toxicity hazard characteristic, unless one or more of the following exception criteria apply. 

• in addition, if the human health exposure band for the introduction is 4 and the chemical is a UV filter, information is required to justify why the chemical would not cause genetic toxicity mediated by UV light. This may include one or more of the following: 
  • the chemical has a molar extinction coefficient/absorption coefficient of less than 1,000 Lmol^-1cm^-1 at wavelengths between 290 and 700 nm (based on the results of a study following OECD test guideline 101), or 
  • results from in vitro phototoxicity studies, or 
  • results from in vitro or in vivo genetic toxicity studies where the methods have been modified to include photoactivation.

More information: Categorisation of UV filters

Example 1 – chemical is a salt of a specified chemical which is on the list of chemicals with high hazards for categorisation, based on carcinogenicity 

Peter wants to introduce the chemical glycine, N,N-bis[2-[bis(carboxymethyl)amino]ethyl]-, sodium salt (1:?) (CAS: 7578-43-0), which is a salt of Glycine, N,N-bis(carboxymethyl)- (CAS: 139-13-9) that is in the table of specified chemicals for carcinogenicity. The proposed introduction has a molecular weight of 415.33 g/mol and therefore does not meet the exception criterion “the salt/ester is a high molecular weight polymer, with low levels of low molecular weight species” nor the exception criterion “the molecular weight of the salt/ester is greater than or equal to 1,000 g/mol”. Thus, Glycine, N,N-bis(2-(bis(carboxymethyl)amino)ethyl)-, sodium salt (CAS: 7578-43-0) is considered to have the human health hazard characteristic carcinogenicity.

Peter’s introduction's human health hazard band is C so he should move on to the next step – step 4.5 Work out your human health risk for categorisation.

Example 2 – chemical is an ester of a specified chemical which is on the list of chemicals with high hazards for categorisation, based on carcinogenicity and genetic toxicity 

Rose wants to introduce an ester of [1,1’-Biphenyl]-2-ol, which has a molecular weight ≥1,000 g/mol. The ester itself is not on the List, but her chemical is an ester of [1,1’-Biphenyl]-2-ol, which is in the tables of specified chemicals for carcinogenicity and genetic toxicity. So she needs to consider whether an exception applies to this chemical. If an exception does not apply, the ester would be considered to have the same high hazard characteristics as [1,1’-Biphenyl]-2-ol (carcinogenicity and genetic toxicity). But because Rose’s chemical has a molecular weight greater than or equal to1,000 g/mol, it meets the exception criteria. 

Rose’s ester is not considered to have the human health hazard characteristics of carcinogenicity and genetic toxicity. 

Rose continues through step 4.4 of the categorisation process and next needs to follow our guidance on checking human health hazard band B hazard characteristics.

Example 3 – polymer is an ester of a specified chemical which is on the list of chemicals with high hazards for categorisation, based on genetic toxicity

Paul wants to introduce a branched polymer containing phenol, 2-amino- bound to side chains via ester linkages. 
The polymer itself is not on the List, but it contains phenol, 2-amino-, which is in the table of specified chemicals for genetic toxicity. So he needs to consider whether an exception applies to this chemical. If an exception does not apply, the polymer would be considered to have the same high hazard characteristics as phenol, 2-amino- (genetic toxicity). 

The number average molecular weight (NAMW) of Paul’s polymer is 4,500 g/mol with 17% by mass having a molecular weight less than 1,000 g/mol and 8% by mass having a molecular weight less than 500 g/mol. The exception criteria for polymers states that there must be low levels of low molecular weight species which means less than 10% (by mass) of molecules with a molecular weight that is less than 500 g/mol and less than 25% (by mass) of molecules with a molecular weight that is less than 1,000 g/mol. Therefore, the polymer meets the exception criteria and is not considered to have the genetic toxicity hazard characteristic. 

Paul continues through step 4.4 of the categorisation process and next needs to follow our guidance on checking human health hazard band B hazard characteristics. 
 

Human health hazard characteristics are split into hazard bands. Hazard characteristics of most concern are in hazard band C, while those of lower concern are in hazard band A. You must always start at hazard band C. Step 4.4 tells you when you can stop working through your chemical's human health hazard characteristics and when you need to check each of them - ie C, B and A.

Hazard band B has 9 hazard characteristics you need to consider:

• High molecular weight polymer that is water absorbing
• Respiratory sensitisation
• Corrosive to the respiratory tract
• Specific target organ toxicity and a single exposure (significant toxicity)
• Skin corrosion
• Eye damage
• Skin sensitisation
• Acute toxicity (fatal or toxic)
• Specific target organ toxicity after repeated exposure

Instructions

You must always start at hazard band C. 

You only need to work through the hazard characteristics on this page if your introduction is in: 

• human health exposure band 3, and you are trying to get to an outcome of very low indicative human health risk or 
• human health exposure band 4, and you are trying to get to an outcome of low or very low indicative human health risk.

Work your way through each hazard characteristic on this page. Look at whether your chemical meets the hazard characteristic definition based on the information that you have.

If it does meet the hazard characteristic definition, stop there - your introduction's human health hazard band is B. Move on to the next step - step 4.5 Work out your human health risk for categorisation.

If it does not meet the hazard characteristic definition, you’ll need to try and prove that your chemical does not have this hazard characteristic. The information that you need to prove this for each hazard characteristic is shown below. If you do not have this information, stop there - your introduction’s human health hazard band is B. Move onto the next step – step 4.5 Work out your human health risk for categorisation.

If you do have this information (so you can prove that the chemical does not have the hazard characteristic), move onto the next hazard characteristic on this page. 

After you have considered all the hazard characteristics on this page and have proven that the chemical does not have any of them, decide whether you can stop there or continue to human health hazard band A This depends on the exposure band of your introduction. 

If your introduction is in human health exposure band 3, continue to human health hazard band A. 

If your introduction is in human health exposure band 4, you can choose to stop (and go to step 4.5 to work out your human health risk for categorisation), or continue to human health hazard band A.

High molecular weight polymer that is water absorbing

High molecular weight polymer that is water absorbing means that all of the following apply to the industrial chemical: 

• it is a high molecular weight polymer, and 
• it has a number average molecular weight that is greater than or equal to 10,000 g/mol, and 
• it is capable of absorbing its own weight, or more, in water, and 
• it contains particles with a particle size less than 10 micrometres (microns).

Information required to demonstrate the absence of the hazard characteristic, high molecular weight polymer that is water absorbing 

If the chemical is a high molecular weight polymer, the information required to demonstrate that it does not have the hazard characteristic, high molecular weight polymer that is water absorbing, is at least one of: 

• molecular weight information that demonstrates the number average molecular weight (NAMW) is less than 10,000 g/mol, or 
• information that demonstrates that the polymer is not introduced in a particulate form, or 
• particle size information that demonstrates that the particle size is greater than or equal to 10 micrometres (microns), or
• information that demonstrates that the polymer does not absorb its own weight or more in water, such as experiments that show that it does not form a gel in water, or that if it does, the gel dissolves upon addition of more water.

Respiratory sensitisation

Respiratory sensitisation means that any of the following apply to the industrial chemical: 

• the chemical is known or presumed to produce hypersensitivity of the airways in humans, as described in chapter 3.4 of the GHS, with the chemical classified as respiratory sensitisation (category 1), or 
• the chemical is named: 
  • on the EU SVHC Candidate list for authorisation, based on respiratory sensitising properties (https://echa.europa.eu/candidate-list-table), or 
  • in the Danish EPA (Q)SAR Database as a predicted respiratory sensitiser (http://qsar.food.dtu.dk/), or 
  • the chemical is an enzyme, or 
  • the chemical is a polymer that contains one or more free isocyanate groups, or 
  • an in vivo study on the chemical indicates hypersensitivity of the airways, as discussed in chapter 3.4 of the GHS, or 
  • an in vitro study on the chemical: 
    • indicates hypersensitivity of the airways, as discussed in chapter 3.4 of the GHS, and 
    • the result of the study has not been negated by in vivo studies conducted on the chemical for hypersensitivity of the airways.

Information required to demonstrate the absence of the hazard characteristic, respiratory sensitisation  

There are no information requirements to demonstrate the absence of the hazard characteristic, respiratory sensitisation. If you do not have any of the information listed above that demonstrates that the chemical has this hazard characteristic then you can assume it does not for the purposes of categorisation.

Note: The information can include that the chemical is an enzyme or a polymer that contains one or more free isocyanate groups. 

Corrosive to the respiratory tract

Corrosive to the respiratory tract means that any of the following apply to the industrial chemical: 

• the chemical is known to cause destruction of the respiratory tract tissue, as described in chapter 3.1 of the GHS, with the chemical classified as corrosive to the respiratory tract (AUH071 - non-GHS hazard statement), or 
• an in vivo study on the chemical conducted following an acceptable test guideline for acute inhalation toxicity, subacute inhalation toxicity or subchronic inhalation toxicity results in destruction of the respiratory tract, as described in chapter 3.1 of the GHS.

Information required to demonstrate the absence of the hazard characteristic, corrosive to the respiratory tract  

There are no information requirements to demonstrate the absence of the hazard characteristic, corrosive to the respiratory tract. If you do not have any of the information listed above that demonstrates that the chemical has this hazard characteristic, then you can assume it does not for the purposes of categorisation.

Specific target organ toxicity after a single exposure (significant toxicity)

Specific target organ toxicity after a single exposure (significant toxicity) means that any of the following apply to the industrial chemical: 

• the chemical is known or presumed to produce significant toxicity in humans, as described in chapter 3.8 of the GHS, with the chemical classified as specific target organ toxicity – single exposure (category 1), or 
• an in vivo study on the chemical: 
  • conducted following an acceptable test guideline for acute oral toxicity results in significant toxic effects of relevance to human health, as discussed in chapter 3.8 of the GHS, at less than or equal to 300 mg/kg bw, or 
  • conducted following an acceptable test guideline for acute dermal toxicity results in significant toxic effects of relevance to human health, as discussed in chapter 3.8 of the GHS, at less than or equal to 1,000 mg/kg bw, or
  • conducted following an acceptable test guideline for acute inhalation toxicity results in significant toxic effects of relevance to human health, as discussed in chapter 3.8 of the GHS:
    • gases - less than or equal to 2,500 ppmV/4h, or 
    • vapours -  less than or equal to mg/L/4h, or 
    • for dusts/mists/fumes - less than or equal to 1 mg/L/4h.

Information required to demonstrate the absence of the hazard characteristic, specific target organ toxicity after a single exposure (significant toxicity) 

There are no information requirements to demonstrate the absence of the hazard characteristic, specific target organ toxicity after a single exposure (significant toxicity). If you do not have any of the information listed above that demonstrates that the chemical has this hazard characteristic, then you can assume it does not for the purposes of categorisation.

Skin corrosion

Skin corrosion means that any of the following apply to the industrial chemical: 

• the chemical is known to produce irreversible damage to the skin, as described in chapter 3.2 of the GHS, with the chemical classified as skin corrosion (category 1), or 
• an in vitro study on the chemical conducted following an acceptable test guideline for skin corrosion results in the prediction of skin corrosion effects, or 
• an in vivo study on the chemical conducted following an acceptable test guideline for skin irritation results in destruction of skin tissue, as described for skin corrosion in chapter 3.2 of the GHS, or 
• the chemical is a pyrophoric liquid or a pyrophoric solid, as described in chapters 2.9 and 2.10 of the GHS respectively. 

Information required to demonstrate the absence of the hazard characteristic, skin corrosion  

The information required to demonstrate that a chemical does not have the hazard characteristic, skin corrosion, is at least one of the following: 

• if the human health exposure band for the introduction is 3 or 4
  • information that demonstrates that the chemical is a high molecular weight polymer that does not contain any of the following reactive functional groups: 
    • anhydride, or
    • epoxide, or 
    • sulfonic acid, or 
    • amine, or 
  • information that demonstrates that the chemical is a high molecular weight polymer that contains any of the following reactive functional groups and the polymer has a combined functional group equivalent weight of greater than or equal to 1,000 g/mol: 
    • anhydride, or 
    • epoxide, or 
    • sulfonic acid, or 
    • amine, or 
  • test results from an in vitro study on the chemical or from suitable read across information, conducted following an acceptable test guideline for skin corrosion, with a non-corrosive prediction, or 
  • test results from an in vitro study on the chemical or from suitable read across information, conducted following an acceptable test guideline for skin irritation, with a non-irritant prediction, or 
  • test results from an in vivo study on the chemical or from suitable read across information, conducted following an acceptable test guideline for skin irritation, which does not result in destruction of skin tissue, as described for skin corrosion in chapter 3.2 of the GHS.
• if the human health exposure band for the introduction is 3 - a suitable in silico prediction indicating that the chemical is not irritating to skin or has no alerting groups for skin irritation.

Eye damage

Eye damage means that any of the following apply to the industrial chemical: 

• the chemical is known to produce serious eye damage, as described in chapter 3.3 of the GHS, with the chemical classified as eye damage (category 1), or 
• an in vitro study on the chemical conducted following an acceptable test guideline for eye damage results in the prediction of serious eye damage effects, or 
• an in vivo study on the chemical conducted following an acceptable test guideline for eye irritation results in effects on the eye, as described for serious eye damage in chapter 3.3 of the GHS, or 
• the chemical is a pyrophoric liquid or a pyrophoric solid, as described in chapters 2.9 and 2.10 of the GHS, respectively. 

Information required to demonstrate the absence of the hazard characteristic, eye damage 

The information required to demonstrate that a chemical does not have the hazard characteristic, eye damage, is at least one of the following: 

• if the human health exposure band for the introduction is 3 or 4
  • information that demonstrates that the chemical is a high molecular weight polymer that does not contain any of the following reactive functional groups: 
    • anhydride, or 
    • epoxide, or 
    • sulfonic acid, or 
    • amine, or
  • information that demonstrates that the chemical is a high molecular weight polymer that contains any of the following reactive functional groups with a combined functional group equivalent weight of greater than or equal to 1,000 g/mol: 
    • anhydride, or 
    • epoxide, or 
    • sulfonic acid, or 
    • amine, or 
  • test results from an in vitro study on the chemical or from suitable read across information, conducted following an acceptable test guideline for eye damage, which predicts the chemical would not induce serious eye damage 
  • test results from an in vivo study on the chemical or from suitable read across information, conducted following an acceptable test guideline for eye irritation, which does not result in effects on the eye, as described for eye damage in chapter 3.3 of the GHS.
• if the human health exposure band for the introduction is 3 - a suitable in silico prediction indicating that the chemical is not irritating to the eye.

Skin sensitisation 

Skin sensitisation means that any of the following apply to the industrial chemical: 

• the chemical is known to cause an allergic response following skin contact, as described in chapter 3.4 of the GHS, with the chemical classified as skin sensitisation (category 1), or 
• human testing or epidemiological studies on the chemical result in evidence of an allergic response, as described in chapter 3.4 of the GHS, or 
• an in vitro study on the chemical: 
  • conducted following an acceptable test guideline for skin sensitisation, results in the prediction of skin sensitisation effects, and 
  • the results of the study have not been negated by in vivo studies conducted on the chemical for skin sensitisation, or 
• an in chemico study on the chemical: 
  • conducted following an acceptable test guideline for skin sensitisation, results in the prediction of skin sensitisation effects, and 
  • the results of the study have not been negated by in vivo studies conducted on the chemical for skin sensitisation, or 
• an in vivo study on the chemical conducted following an acceptable test guideline for skin sensitisation, results in the induction of an allergic response, as described in chapter 3.4 of the GHS.

Information required to demonstrate the absence of the hazard characteristic, skin sensitisation  

• There are no information requirements to demonstrate the absence of the hazard characteristic, skin sensitisation, if the chemical is corrosive to the skin (GHS category 1) as the in vivo tests cannot be conducted 
• otherwise, if the human health exposure band is 3 or 4, the information required to demonstrate that a chemical does not have the hazard characteristic, skin sensitisation, is at least one of the following:  
  • information that demonstrates that the chemical is a high molecular weight polymer for which at least one of the following applies: 
    • it contains only low concern reactive functional groups, or 
    • it contains only low concern reactive functional groups and unsubstituted positions ortho and para to phenolic hydroxyl groups, or  
    • the only reactive functional groups it contains are unsubstituted positions ortho and para to phenolic hydroxyl groups, or 
    • it contains only low and moderate concern reactive functional groups , with a combined functional group equivalent weight of greater than or equal to 1000 g/mol, or 
    • it contains only moderate concern reactive functional groups, with a combined functional group equivalent weight of greater than or equal to 1000 g/mol, or 
    • it has a number average molecular weight that is greater than or equal to 10,000 g/mol and both: 
      • less than 2% by mass of molecules with molecular weight that is less than 500 g/mol, and 
      • less than 5% by mass of molecules with molecular weight that is less than 1,000 g/mol, or 
  • information that demonstrates that the chemical is a substance covered by Entry 9 of Annex V, of the REACH Regulation, or 
  • results from a defined approach (combination of tests) described in OECD TG 497, with a non-sensitising prediction*, or
  • all of the following: 
    • test results from an in chemico test on the chemical or from suitable read-across information, conducted following an acceptable test guideline for the 1st key event in the adverse outcome pathway for skin sensitisation, with a non-sensitising prediction, and 
    • test results from an in vitro study on the chemical or from suitable read across information, conducted following an acceptable test guideline for the 2nd key event in the adverse outcome pathway for skin sensitisation, with a non-sensitising prediction, and 
    • test results from an in vitro study on the chemical or from suitable read across information, conducted following an acceptable test guideline for the 3rd key event in the adverse outcome pathway for skin sensitisation, with a non-sensitising prediction
  • test results from an in vivo study on the chemical or from suitable read-across information, conducted following an acceptable test guideline for skin sensitisation, which does not result in induction of an allergic response, as described in chapter 3.4 of the GHS 
• in addition, if the human health exposure band for the introduction is 4 and the chemical is a UV filter or is introduced for an end use in a tattoo ink, information is required to justify why the chemical would not cause skin sensitisation mediated by UV light. This may include one or more of the following : 
  • the chemical has a molar extinction coefficient/absorption coefficient of less than 1,000Lmol-¹cm-¹ at wavelengths between 290 and 700nm (based on the results of a study following OECD test guideline 101), or 
  • results from in vitro phototoxicity studies, or 
  • results from in vitro or in vivo skin sensitisation studies where the methods have been modified to include photoactivation.

Low concern reactive functional groups - see our polymer of low concern criteria page.

Moderate concern reactive functional groups - see our polymer of low concern criteria page. 

*Note that negative results only with key event 1 and key event 2 adverse outcome pathway (AOP) assays will not rule out skin sensitisation potential for some weak skin sensitisers and pre-/pro-hapten fragrance chemicals when using the "2 out of 3" (2o3) defined approach and hence this should be considered when determining an appropriate testing methodology. For further information see: ENV/CBC/MONO(2021)11. Supporting Document to the OECD Guideline 497 on Defined Approaches for Skin Sensitisation

Acute toxicity (fatal or toxic) 

Acute toxicity (fatal or toxic) means that any of the following apply to the industrial chemical: 

• the chemical is known to exhibit acute toxicity effects, as described in chapter 3.1 of the GHS, with the chemical classified as acute toxicity (category 1 or 2 or 3), or
• an in vitro study on the chemical: 
  • conducted following an acceptable test guideline for acute oral toxicity, results in a predicted acute oral toxicity LD50 value of less than or equal to 300 mg/kg bw, and 
  • the results of the study have not been negated by in vivo studies conducted on the chemical for acute toxicity, or 
• an in vivo study on the chemical: 
  • conducted following an acceptable test guideline for acute oral toxicity results in an acute oral LD50 value of less than or equal to 300 mg/kg bw, or 
  • conducted following an acceptable test guideline for acute dermal toxicity results in an acute dermal LD50 value of less than or equal to 1,000 mg/kg bw, or 
  • conducted following an acceptable test guideline for acute inhalation toxicity results in an acute inhalation LC50 value of:
    • for gases - less than or equal to 2,500 ppmV/4h, or 
    • for vapours - less than or equal to 10 mg/L/4h, or 
    • for dusts/mists/fumes - less than equal to 1 mg/L/4h , or 
• evidence in humans of systemic toxicity after eye contact, with the chemical classified with the non-GHS hazard statement – AUH070, or 
• an in vivo study, conducted following an acceptable test guideline for eye irritation, results in overt signs of systemic toxicity or mortality, which is likely to be attributed to absorption of the chemical through the mucous membranes of the eye, with the chemical classified with the non-GHS hazard statement – AUH070.

Information required to demonstrate the absence of the hazard characteristic, acute toxicity (fatal or toxic) 

• there are no information requirements to demonstrate the absence of the hazard characteristic, acute toxicity (fatal or toxic), if the chemical is corrosive to the skin (GHS category 1), or likely to be corrosive to the skin (that is, the chemical is a strong acid (pH less than or equal to 2.0) or base (pH greater than or equal to 11.5), and has high buffering capacity (if relevant)), as the in vivo tests cannot be conducted
• otherwise, the information required to demonstrate that a chemical does not have the hazard characteristic, acute toxicity (fatal or toxic), is at least one of the following: 
  • if the human health exposure band for the introduction is 3 - both of the following: 
    • a suitable in silico prediction for acute toxicity (LD50) of the chemical of greater than 2,000 mg/kg bw/day, and 
    • test results from an in vitro study on the chemical or from suitable read across information for acute toxicity (LD50), conducted following an acceptable test guideline for acute oral toxicity, of greater than 300 mg/kg bw,  or 
  • if the human health exposure band for the introduction is 3 or 4
    • information that demonstrates that the chemical is a high molecular weight polymer that has:
      • less than 5% by mass of molecules with molecular weight less than 1,000 g/mol, and 
      • less than 2% by mass of molecules with molecular weight less than 500 g/mol, or 
  • inclusion of the chemical in the Select Committee on GRAS Substances (SCOGS) Database as a Type 1 conclusion, as long as the human health exposure expected from the industrial use of the chemical is no higher than the human health exposure expected from food use, or 
  • the chemical has been notified to the US FDA GRAS notification program and FDA had no questions about the notifier’s conclusion of GRAS status, as long as the human health exposure expected from the industrial use of the chemical is no higher than the human health exposure expected from food use, or 
  • the chemical is permitted to be used as a food additive according to Schedule 15 of the Australia New Zealand Food Standards Code - Standard 1.3.1 - Food Additives, as long as the human health exposure expected from the industrial use of the chemical is no higher than the human health exposure expected from food use, or 
  • information that demonstrates that the chemical is a substance covered by Entry 9 of Annex V of the REACH Regulation, or 
  • a test result from at least one in vivo study on the chemical or from suitable read across information, as detailed below, with the administration route dependent on the most relevant route of exposure (or the oral route if information on the most relevant route is not available): 
    • conducted following an acceptable test guideline for acute oral toxicity with an LD50 greater than 300 mg/kg bw, or
    • conducted following an acceptable test guideline for acute dermal toxicity with an LD50 greater than 1,000 mg/kg bw, or 
    • conducted following an acceptable test guideline for acute inhalation toxicity, with an LC50: 
      • for gases -  greater than 2,500 ppmV/4h, or
      • for vapours - greater than 10 mg/L/4h, or 
      • for dusts/mists/fumes - greater than 1 mg/L/4h, or 
  • test results from an in vivo study via the oral route on the chemical or from suitable read across information, conducted following an acceptable test guideline for subacute oral toxicity, with a NOAEL greater than or equal to 1,000 mg/kg bw/day.

Specific target organ toxicity after repeated exposure

Specific target organ toxicity after repeated exposure means that any of the following apply to the industrial chemical:

• the chemical is known to exhibit significant toxicity or be potentially harmful to human health following repeated exposure, as described in chapter 3.9 of the GHS, with the chemical classified as specific target organ toxicity – repeated exposure (category 1 or 2), or 
• an in vivo study on the chemical: 
  • conducted following an acceptable test guideline for subacute oral toxicity results in significant toxic effects of relevance to human health, as discussed in chapter 3.9 of the GHS, and a NOAEL (oral) value of less than 300 mg/kg bw/day, or 
  • conducted following an acceptable test guideline for subchronic oral toxicity results in significant toxic effects of relevance to human health, as discussed in chapter 3.9 of the GHS, and a NOAEL (oral) of less than 100 mg/kg bw/day, or 
  • conducted following an acceptable test guideline for subacute dermal toxicity results in significant toxic effects of relevance to human health, as discussed in chapter 3.9 of the GHS, and a NOAEL (dermal) value of less than 600 mg/kg bw/day, or
  • conducted following an acceptable test guideline for subchronic dermal toxicity results in significant toxic effects of relevance to human health, as discussed in chapter 3.9 of the GHS, and a NOAEL (dermal) of less than 200 mg/kg bw/day, or 
  • conducted following an acceptable test guideline for subacute inhalation toxicity results in significant toxic effects of relevance to human health, as discussed in chapter 3.9 of the GHS, and a NOAEC (inhalation) of: 
    • for gases - less than 750 ppmV/6 h/day, or
    • for vapours - less than 3 mg/L/6 h/day, or 
    • for dusts/mists/fumes less than 0.6 mg/L/6 h/day, or 
  • conducted following an acceptable test guideline for subchronic inhalation toxicity results in significant toxic effects of relevance to human health, as discussed in chapter 3.9 of the GHS, and a NOAEC (inhalation) of: 
    • for gases - less than 250 ppmV/6 h/day, or 
    • for vapours - less than 1 mg/L/6 h/day, or
    • for dusts/mists/fumes less than 0.2 mg/L/6 h/day.

Information required to demonstrate the absence of the hazard characteristic, specific target organ toxicity after repeated exposure  

Information is required to demonstrate the absence of the hazard characteristic, specific target organ toxicity after repeated exposure, if: 

• the human health exposure band for the introduction is 4, and 
• you are seeking to demonstrate that the introduction meets the criteria for low risk or very low risk 

and any of the following apply: 

1. the human health categorisation volume for the introduction is greater than 100 kg and the chemical is introduced for end use in any of the following types of articles: 
   • food contact, or
   • children’s toys that can be placed in the mouth, or 
   • children’s care products that can be placed in the mouth, or 
2. the human health categorisation volume for the introduction is greater than 1000 kg and the chemical is not introduced for end use in any of the following types of articles: 
   • food contact, or 
   • children’s toys that can be placed in the mouth, or 
   • children’s care products that can be placed in the mouth. 

See extra guidance on categorisation of chemicals:

• with an end use in articles that are children's toys or care products 
• with an end use in articles with food contact

If 1 or 2 apply, the information required to demonstrate that a chemical does not have the hazard characteristic, specific target organ toxicity after repeated exposure, is at least one of the following: 

• inclusion of the chemical in the Select Committee on GRAS Substances (SCOGS) Database as a Type 1 conclusion, as long as the human health exposure expected from the industrial use of the chemical is no higher than the human health exposure expected from food use, or 
• the chemical has been notified to the US FDA GRAS notification program and FDA had no questions about the notifier’s conclusion of GRAS status, as long as the human health exposure expected from the industrial use of the chemical is no higher than the human health exposure expected from food use, or 
• the chemical is permitted to be used as a food additive according to Schedule 15 of the Australia New Zealand Food Standards Code - Standard 1.3.1 - Food Additives, as long as the human health exposure expected from the industrial use of the chemical is no higher than the human health exposure expected from food use, or 
• information that demonstrates that the chemical is a substance covered by Entry 9 of Annex V of the REACH Regulation, or 
• information that demonstrates that the chemical is a high molecular weight polymer that has 
  • < 5% by mass of molecules with molecular weight < 1000 g/mol, and
  • < 2% by mass of molecules with molecular weight < 500 g/mol, or
• a test result from at least one in vivo study on the chemical or from suitable read across information, as detailed below, with the administration route dependent on the most relevant route of exposure (or the oral route if information on the most relevant route is not available): 
  • conducted following an acceptable test guideline for subacute oral toxicity, in which the NOAEL (oral) is greater than or equal to 300 mg/kg bw/day or there were no significant toxic effects of relevance to human health (as described in chapter 3.9 of the GHS) produced, or 
  • conducted following an acceptable test guideline for subchronic oral toxicity, in which the NOAEL (oral) is greater than or equal to 100 mg/kg bw/day or there were no significant toxic effects of relevance to human health (as described in chapter 3.9 of the GHS) produced, or 
  • conducted following an acceptable test guideline for subacute dermal toxicity, in which the NOAEL (dermal) is greater than or equal to 600 mg/kg bw/day or there were no significant toxic effects of relevance to human health (as described in chapter 3.9 of the GHS) produced, or 
  • conducted following an acceptable test guideline for subchronic dermal toxicity, in which the NOAEL (dermal) is greater than or equal to 200 mg/kg bw/day or there were no significant toxic effects of relevance to human health (as described in chapter 3.9 of the GHS) produced, or 
  • conducted following an acceptable test guideline for subacute inhalation toxicity, in which there were no significant toxic effects of relevance to human health (as described in chapter 3.9 of the GHS) produced, or the NOAEC (inhalation) is: 
    • for gases - greater than or equal to 750 ppmV/6 h/day, or 
    • for vapours - greater than or equal to 3 mg/L/6 h/day, or 
    • for dusts/mists/fumes - greater than or equal to 0.6 mg/L/6 h/day , or 
  • conducted following an acceptable test guideline for subchronic inhalation toxicity, in which there were no significant toxic effects of relevance to human health (as described in chapter 3.9 of the GHS) produced, or the NOAEC (inhalation) is: 
    • for gases - greater than or equal to 250 ppmV/6 h/day, or 
    • for vapours - greater than or equal to 1 mg/L/6 h/day, or 
    • for dusts/mists/fumes - greater than or equal to 0.2 mg/L/6 h/day.

There are no information requirements to demonstrate the absence of the hazard characteristic, specific target organ toxicity after repeated exposure, if: 

• the human health exposure band for the introduction is 4, and 
• you are seeking to demonstrate that the introduction meets the criteria for low risk or very low risk, 

and any of the following apply: 

• the human health categorisation volume for the introduction is less than or equal to 100 kg and the chemical is introduced for end use in any of the following types of articles: 
  • food contact, or
  • children’s toys that can be placed in the mouth, or
  • children’s care products that can be placed in the mouth, or 
• the human health categorisation volume for the introduction is less than or equal to 1,000 kg and the chemical is not introduced for end use in any of the following types of articles:
  • food contact, or 
  • children’s toys that can be placed in the mouth, or 
  • children’s care products that can be placed in the mouth

In these circumstances, if you do not have any information that demonstrates that the chemical has this hazard characteristic then you can assume it does not for the purposes of categorisation.

High molecular weight polymer that has lung overloading potential means that all of the following apply to the industrial chemical: 

• it is a polymer, and 
• it has a number average molecular weight that is greater than 70,000 g/mol, and 
• it has a solubility in water of less than 0.1 mg/L, and 
• it becomes aerosolised during end use.

Information required to demonstrate the absence of the hazard characteristic, high molecular weight polymer that has lung overloading potential  

If the chemical is a polymer, the information required to demonstrate that a chemical does not have the hazard characteristic, high molecular weight polymer that has lung overloading potential, is at least one of the following: 

• molecular weight information that demonstrates that the number average molecular weight is less than or equal to 70,000 g/mol, or 
• information that demonstrates that the polymer has a solubility in water that is greater than or equal to 0.1 mg/L measured following an acceptable test guideline for water solubility, or 
• information that demonstrates that the polymer does not become aerosolised during end use

Aspiration hazard

Aspiration hazard means that any of the following apply to the industrial chemical:

• the chemical is known or presumed to cause aspiration toxicity, as described in chapter 3.10 of the GHS, with the chemical classified as may be fatal if swallowed and enters airways (category 1), or 
• the chemical is a hydrocarbon that has a kinematic viscosity less than or equal to 20.5 mm2/s, measured at 40°C.

Information required to demonstrate the absence of the hazard characteristic, aspiration hazard  

• If the chemical is a hydrocarbon, the information required to demonstrate the absence of the hazard characteristic, aspiration hazard, is a measured kinematic viscosity greater than a 20.5mm²/s, at 40 °C 
• Otherwise, there are no information requirements to demonstrate the absence of the hazard characteristic, aspiration hazard. If you do not have any information that demonstrates that the chemical has this hazard characteristic, then you can assume it does not for the purposes of categorisation.

Specific target organ toxicity after a single exposure (harmful or transient effects)

Specific target organ toxicity after a single exposure (harmful or transient effects) means that any of the following apply to the industrial chemical: 

• the chemical is known or presumed to be harmful to humans or to cause transient target organ effects, as described in chapter 3.8 of the GHS, with the chemical classified as specific target organ toxicity-single exposure (category 2 or 3), or 
• an in vivo study on the chemical: 
  • conducted following an acceptable test guideline for acute oral toxicity results in significant toxic effects of relevance to human health, as discussed in chapter 3.8 of the GHS, at greater than 300 but less than or equal to 2,000 mg/kg bw, or 
  • conducted following an acceptable test guideline for acute dermal toxicity results in significant toxic effects of relevance to human health, as discussed in chapter 3.8 of the GHS, at greater than 1,000 but less than or equal to 2,000 mg/kg bw, or 
  • conducted following an acceptable test guideline for acute inhalation toxicity results in significant toxic effects of relevance to human health, as discussed in chapter 3.8 of the GHS, at: 
    • for gases - greater than 2,500 but less than or equal to 20,000 ppmV/4h, or 
    • for vapours - greater than 10 but less than or equal to 20 mg/L/4h, or 
    • for dusts/mists/fumes - greater than 1 but less than or equal to 5 mg/L/4h.

Information required to demonstrate the absence of the hazard characteristic, specific target organ toxicity after a single exposure (harmful or transient effects)  

There are no information requirements to demonstrate the absence of the hazard characteristic, specific target organ toxicity after a single exposure (harmful or transient effects). If you do not have any information that demonstrates that the chemical has this hazard characteristic, then you can assume it does not for the purposes of categorisation. 

Skin irritation 

Skin irritation means that any of the following apply to the industrial chemical: 

• the chemical is known to produce reversible damage to the skin, as described in chapter 3.2 of the GHS, with the chemical classified as skin irritation (category 2), or 
• an in vitro study on the chemical conducted following an acceptable test guideline for skin irritation results in the prediction of skin irritation effects, or 
• an in vivo study on the chemical conducted following an acceptable test guideline for skin irritation results in skin reactions, as described for skin irritation (category 2) in chapter 3.2 of the GHS.

Information required to demonstrate the absence of the hazard characteristic, skin irritation  

The information required to demonstrate that a chemical does not have the hazard characteristic, skin irritation, is at least one of the following: 

• if the human health exposure band for the introduction is 3 - a suitable in silico prediction indicating that the chemical is not irritating to the skin, or 
• test results from an in vitro study on the chemical or from suitable read across information, conducted following an acceptable test guideline for skin irritation, with a non-irritant prediction, or 
• if the human health exposure band for the introduction is 3 or 4 
  • test results from an in vitro study on the chemical or from suitable read across information, conducted following an acceptable test guideline for skin irritation, with a non-irritant prediction, or 
  • test results from an in vivo study on the chemical or from suitable read across information, conducted following an acceptable test guideline for skin irritation, which does not result in skin reactions, as described for skin irritation (category 2) in chapter 3.2 of the GHS, or 
  • test results from an in vivo study on the chemical or from suitable read across information conducted following an acceptable test guideline for acute dermal toxicity, that when tested at 2,000 mg/kg bw/day is not irritating to the skin.

In addition, if the chemical is introduced for an end use in a tattoo ink, information is required to justify why the chemical would not cause skin irritation mediated by UV light. This may include one or more of the following: 

• the chemical has a molar extinction coefficient/absorption coefficient of less than 1,000Lmol-1cm-1 at wavelengths between 290 and 700 nm (based on the results of a study following OECD test guideline 101), or 
• results from in vitro phototoxicity studies, or  
• results from in vitro or in vivo irritation studies where the methods have been modified to include photoactivation.
   

Eye irritation

Eye irritation means that any of the following apply to the industrial chemical: 

• the chemical is known to produce changes in the eye, as described in chapter 3.3 of the GHS, with the chemical classified as eye irritation (category 2), or 
• an in vitro study on the chemical conducted following an acceptable test guideline for eye irritation results in the prediction of eye irritation effects, or 
• an in vivo study on the chemical conducted following an acceptable test guideline for eye irritation results in changes in the eye, as described for eye irritation in chapter 3.3 of the GHS.

Information required to demonstrate the absence of the hazard characteristic, eye irritation  

The information required to demonstrate that a chemical does not have the hazard characteristic, eye irritation, is at least one of the following: 

• if the human health exposure band for the introduction is 3 - a suitable in silico prediction indicating that the chemical is not irritating to the eyes, or 
• if the human health exposure band for the introduction is 3 or 4
  • test results from an in vitro study on the chemical or from suitable read across information, conducted following an acceptable test guideline for eye damage or eye irritation with a non-irritant prediction, or 
  • test results from an in vivo study on the chemical or from suitable read across information, conducted following an acceptable test guideline for eye irritation, which does not result in changes in the eyes, as described for eye irritation (category 2) in chapter 3.3 of the GHS. 

Acute toxicity (harmful) 

Acute toxicity (harmful) means that any of the following apply to the industrial chemical: 

• the chemical is known to exhibit acute toxicity effects, as described in chapter 3.1 of the GHS, with the chemical classified as acute toxicity (category 4), or 
• an in vitro study on the chemical: 
  • conducted following an acceptable test guideline for acute oral toxicity, results in a predicted acute toxicity LD50 value of greater than 300 but less than or equal to 2,000 mg/kg bw, and 
  • the results of the study have not been negated by in vivo studies conducted on the chemical for acute toxicity, or 
• an in vivo study on the chemical: 
  • conducted following an acceptable test guideline for acute oral toxicity results in an acute oral LD50 value of greater than 300 but less than or equal to 2,000 mg/kg bw, or 
  • conducted following an acceptable test guideline for acute dermal toxicity results in an acute dermal LD50 value of greater than 1,000 but less than or equal to 2,000 mg/kg bw, or 
  • conducted following an acceptable test guideline for acute inhalation toxicity results in an acute inhalation LC50 value of: 
    • for gases - greater than 2500 but less than or equal to 20,000 ppmV/4h, or 
    • for vapours - greater than 10 but less than or equal to 20 mg/L/4h, or 
    • for dusts/mists/fumes - greater than 1 but less than or equal to 5 mg/L/4h.

Information required to demonstrate the absence of the hazard characteristic, acute toxicity (harmful)  

• the information required to demonstrate that a chemical does not have the hazard characteristic, acute toxicity (harmful), is at least one of the following: 
  • if the human health exposure band for the introduction is 3 -  both of the following: 
    • a suitable in silico prediction for acute toxicity (LD50) of the chemical of greater than 2,000 mg/kg bw/day, and 
    • test results from an in vitro study on the chemical or from suitable read across information, conducted following an acceptable test guideline for acute oral toxicity, with a predicted LD50 of greater than 2,000 mg/kg bw, or 
  • if the human health exposure band for the introduction is 3 or 4
    • information that demonstrates that the chemical is a high molecular weight polymer that has: 
      • less than 5% by mass of molecules with molecular weight less than 1,000 g/mol, and 
      • less than 2% by mass of molecules with molecular weight less than 500 g/mol 
    • inclusion of the chemical in the Select Committee on GRAS Substances (SCOGS) Database as a Type 1 conclusion, as long as the human health exposure expected from the industrial use of the chemical is no higher than the human health exposure expected from food use, or 
    • the chemical has been notified to the US FDA GRAS notification program and FDA had no questions about the notifier’s conclusion of GRAS status, as long as the human health exposure expected from the industrial use of the chemical is no higher than the human health exposure expected from food use, or 
    • the chemical is permitted to be used as a food additive according to Schedule 15 of the Australia New Zealand Food Standards Code - Standard 1.3.1 - Food Additives, as long as the human health exposure expected from the industrial use of the chemical is no higher than the human health exposure expected from food use, or 
    • information that demonstrates that the chemical is a substance covered by Entry 9 of Annex V of the REACH Regulation, or 
    • a test result from at least one in vivo study on the chemical or from suitable read across information, as detailed below, with the administration route dependent on the most relevant route of exposure (or the oral route if information on the most relevant route is not available): 
      • conducted following an acceptable test guideline for acute oral toxicity with an LD50  greater than 2,000 mg/kg bw, or 
      • conducted following an acceptable test guideline for acute dermal toxicity with an LD50  greater than 2,000 mg/kg bw, or 
      • conducted following an acceptable test guideline for acute inhalation toxicity with an LC50: 
        • for gases - greater than 20,000 ppmV/4h, or 
        • for vapours - greater than 20 mg/L/4h, or 
        • for dusts/mists/fumes - greater than 5 mg/L/4h, or
    • test results from an in vivo study on the chemical or from suitable read across information, conducted following an acceptable test guideline for subacute oral toxicity, with a NOAEL greater than or equal to 1,000 mg/kg bw/day.