Schedule Part C - STD notification health and environmental effects

This part of the schedule specifies the health and environmental effects data you must submit as part of your Standard Notification application.

You must provide complete study reports.

Notes:

  1. Ideally, toxicity tests must be carried out in accordance with OECD Guidelines for the Testing of Chemicals or equivalent guidelines.
  2. To assist, the numbers in brackets after each test detailed below are the OECD guideline method numbers most appropriate to use for that endpoint, although they are not necessarily the only OECD guideline that can be used. Links to each are also provided.

Go to OECD Guildelines for testing of chemicals

Acute toxicity data

Information on the acute toxicity of the chemical will give a measure of the toxic effects following short-term exposure and may indicate specific toxic effects and possible mode of action.

Tests must be relevant to the physical properties of the chemical and consider the way in which the chemical is to be used.

Exact LD50 values are not mandatory requirements and procedures such as a limit test to determine a minimum LD50 are acceptable.

Acute oral toxicity (TG 401 or equivalent)

Acute oral toxicity testing provides information on the health hazards likely to arise from short-term exposure by the oral route. The results may provide information on the chemical's mode of toxic action.

You must provide information and data that covers:

  • some quantitative measure of toxicity with an indication of accuracy
  • test animal used, indicating number, species/strain and sex
  • the nature of the dosed material (for example, solution or suspension—provide details of the vehicle used, if any )
  • method
  • results of testing, including:
    • tabulation of response data by number, sex and dose level
    • toxic effects seen, time of onset and duration
    • time of death after dosing
    • slope of dose-mortality curve, where possible
    • effects on the organs (for example, gross findings at autopsy and histological data).

Acute dermal toxicity (TG 402 or equivalent)

Acute dermal toxicity testing provides information on the health hazards likely to arise from short-term exposure to the skin. The results may provide information on dermal absorption and the chemical's mode of toxic action by this route.

You must provide information and data that covers:

  • some quantitative measure of toxicity with some indication of accuracy
  • test animal used, indicating number, species/strain and sex
  • the nature of the dosed material (for example, solution or suspension—provide details of the vehicle used, if any)
  • method
  • results of testing, including:
    • tabulation of response data by number, sex and dose level
    • toxic effects seen, time of onset and duration
    • time of death after dosing
    • slope of dose-mortality curve, where possible
    • effects on the organs, (for example, gross findings at autopsy and histological data).

Acute inhalation toxicity (TG 403 or equivalent)

The acute inhalation toxicity of the chemical, such as a gas, volatile substance or aerosol/particulate, provides information on health hazards likely to arise from short-term exposure by inhalation. The results may provide additional information on the chemical's mode of toxic action.

You must provide information and data that covers:

  • some quantitative measure of toxicity with some indication of accuracy
  • test animal used, indicating number, species/strain and sex
  • nature of dosed material, with particle size if aerosol or particulate
  • method
  • results of testing, including:
    • tabulation of response data by number, sex and dose level
    • toxic effects seen, time of onset and duration
    • time of death after dosing
    • slope of dose-mortality curve, where possible
    • effects on the organs (for example, gross findings at autopsy and histological data).

Irritation and corrosion

You must provide information derived from irritation testing that indicates the hazards likely to arise from exposure of the skin, eyes and mucous membranes to the chemical.

Chemicals that have predictable corrosive potential based on physico-chemical properties, such as strong acidity or alkalinity, are often not tested in animals for irritation. Such chemicals are instead classified as hazardous based on their physico-chemical properties.

Skin irritation (TG 404 or equivalent)

A finding of dermal irritation by the chemical on the skin of mammals indicates that hazards are likely to arise from exposure of human skin to the chemical.

You must ensure the dermal irritation assessment is conducted in conjunction with an assessment of the nature, intensity and reversibility of the observed response.

You must provide information and data that covers:

  • test animal used, indicating number, species/strain and sex
  • method
  • form of the dose
  • results of testing, including:
    • tabulation of response data by number, sex and dose level for each observation time period (for example, 30 to 60 minutes, 24, 48 and 72 hours after patch removal)
    • description of any lesions observed, together with the onset time and recovery period.

Data from a validated in vitro test (such as TG 439) is also accepted by NICNAS. You must provide information and data that covers:

  • the test system used
  • method
  • results of testing

Eye irritation (TG 405 or equivalent)

Results of animal eye irritation studies can help to predict hazards likely to arise from exposure of human eyes and associated mucous membranes. You must provide an assessment of the severity of acute eye irritation.

You must ensure the eye irritation test is conducted in conjunction with an assessment of the nature and reversibility of the response observed.

You must provide information and data that covers:

  • test animal used, indicating number, species/strain and sex
  • method
  • physica nature and, where applicable, concentration and pH value for the test substance
  • results of testing, including:
    • tabulation of response data by number and sex at each observation time (for example, 1, 24, 48 and 72 hours)
    • a description of the degree and nature of irritation and corrosion on the cornea, iris and conjunctiva, with time onset, severity and recovery period.
    • Data from a validated in vitro test (such as TG 437 or 438) is also accepted by NICNAS. You must provide information and data that covers:
  • the test system used
  • method
  • results of testing

Due to the validation status of the in vitro eye irritation methods, if the result from the in vitro test is negative animal testing will be required.

Sensitisation

Skin sensitisation (TG 406 or 429 or equivalent)

The potential of a chemical to provoke a skin sensitisation reaction (dermal sensitisation or allergic contact dermatitis) can help to predict the possible hazard to a human population repeatedly exposed to the chemical.

In animal studies, the preferred sensitisation test is the local lymph node assay (OECD TG 429). Other acceptable methods include the Magnusson and Kligman Guinea-Pig Maximisation Test, which uses an adjuvant, and the Buehler Test, also in guinea pigs, but without an adjuvant.

For animal studies, you must provide information and data that covers:

  • test animal used, indicating number, species and/or strain and sex
  • method
  • results of testing, including:
    • tabulation of response data by number, sex and age of treated and control animals
    • dose level administered at each stage
    • whether irritation occurred during induction stages and any histological abnormality at test conclusion.

You must provide details of human patch test methods and results, if these have been conducted.

Respiratory sensitisation

No standard OECD guidelines are available for determining the respiratory sensitising potential of chemicals in animals. You must submit non-standard studies, if they are available, and any human evidence regarding this effect.

Repeated dose toxicity (TG 407, TG 410, TG 412 or equivalent)

Repeated dose toxicity data provides information on health hazards likely to arise from repeated exposures over a limited period. The basic study used for repeated dose toxicity is normally the 28-day oral study (TG 407 or equivalent). This study may provide information on neurological effects, immunological effects and reproductive organ toxicity.

Where toxicity arising from dermal absorption has been observed in acute toxicity studies and human skin contact is likely during use of the chemical, a 21-day to 28-day repeated dose dermal toxicity study (TG 410 or equivalent) must be conducted to provide information on possible health hazards likely to arise from repeated skin contact.

Similarly, where toxicity arising from inhalation has been observed in acute toxicity studies, and inhalation by humans is likely during use of the chemical, a 28-day repeated dose inhalation toxicity study (TG 412 or equivalent) must be conducted to provide information on health hazards likely to arise from repeated inhalation.

You must provide data from each study that includes:

  • test animal used, indicating number, species and strain and sex
  • dosing vehicle, if any
  • route and frequency of administration
  • method
  • results of testing, including:
    • tabulation of toxic response data by number, sex and dose
    • description of effects observed on the animal and its organs, including clinical biochemistry and pathology investigations (signs of toxicity, their time and onset of duration, whether the effects were reversible and necropsy and histological findings)
    • discussion of study results and conclusions.

Genetic toxicology

The primary function of genotoxic testing is to investigate the potential of the chemical to induce mutations in the human genome and the potential for mutations to be transmitted through the germ cells to future generations.

You must organise for testing that demonstrates:

  • the chemical's ability to induce point mutations in established microbial systems
  • any production by the chemical of chromosome damage in mammalian cells grown in vitro.

You may select a number of tests in each group. You can source a list of tests from the OECD Guidelines on Genetic Toxicology Testing and Guidance on the Selection and Application of Assays or use equivalent or appropriate tests from other recognised protocols.

Select tests depending on the:

  • nature of the chemical
  • extent of its eventual distribution and use
  • data from other toxicological tests and toxicokinetic studies
  • available technical expertise.

If either of the in vitro tests gives positive results you will need to provide data from a relevant in vivo genotoxicity test. You should choose the relevant in vivo test based on the effects observed in vitro.

Induction of point mutations (TG 471 or equivalent)

You must provide data from a test to demonstrate the induction of point mutations (base-pair change and frame shift mutations) in established microbial test systems, with and without the use of appropriate metabolic activation systems.

Genotoxic damage in vivo (TG 474 or equivalent)

You must provide data from a suitable test to detect the production of genotoxic damage in vivo, for example test method TG 474, Mammalian Erythrocyte Micronucleus Test.

You may not need to provide this data if both in vitro tests (induction of point mutations and chromosome damage) are negative.

Chromosome damage (TG 473, TG 474, TG 479 or equivalent)

You must provide data from a test to demonstrate the production of chromosome damage in appropriate mammalian cells grown in vitro, with and without the use of metabolic activation systems. Suggested methods include TG 473 In vitro Mammalian Chromosome Aberration Test and TG 479 In vitro SisterChromatid Exchange Assay in Mammalian Cells.

Ecotoxicity data

You need to provide information on the ecotoxicity of the chemical, to give a measure of the toxic effects on biotic systems.

When it is not possible to provide ecotoxicity data through testing of the chemical or a suitable analogue you can provide estimates derived from QSAR calculations. However, NICNAS will only accept QSAR calculations for ecotoxicity properties when information on the input parameters and calculation methods used are available for analysis. This ensures the methods used and results obtained are valid.

Fish, acute toxicity test (TG 203 or equivalent)

This assessment of the acute toxicity of the chemical to fish is made after continuously exposing them to a series of concentrations of the chemical in water over four days. Mortalities and abnormal responses are recorded over this period.

You must provide information and data that covers:

  • measure of toxicity, for example, LC50 (in mg/L), with confidence limits
  • number and species of fish used
  • duration of exposure
  • no-effect level (in mg/L)
  • method
  • results of testing, including:
    • tabulation of mortality against concentration according to observation time
    • concentration-mortality curve at end of test.

Daphnia, acute immobilisation test and reproduction test (TG 202 or equivalent)

This assessment of the toxicity of the chemical to aquatic invertebrates is made by exposing daphnids to a series of concentrations of the chemical in water. This test has two phases:

  • acute,which gives:
    • 24-hour EC50 value
    • highest concentration causing no immobilisation
    • lowest concentration causing 100% immobilisation
  • reproduction,which gives:
    • EC50 (immobilisation) values over period of 1 to 14 days
    • no observed effect concentration (in mg/L)
    • other information based on reproduction observations.

You must provide information and data that covers:

  • number and species of Daphnia used
  • duration of exposure
  • concentrations used
  • description of the methods used
  • tabulation of concentration-response time results.

You must provide a Daphnia sp.reproduction test, especially when acute toxicity and exposure to the aquatic compartment are both high. In the absence of this part of the test, you can submit a variation to the data requirements, along with a supporting scientific argument to fully justify the omission (for example, limited aquatic exposure).

Algal Growth Inhibition Test (TG 201 or equivalent)

This assessment of the potential effects of the chemical on the natural environment is made by exposing algae to a series of concentrations over at least three days.

Algae growth is determined after each day, and the algae concentration per mL is calculated for each time and concentration. An assessment can be based on the 72-hour EC50 value and the growth concentration curves.

You must provide information and data that covers:

  • test organisms used (for example, origin, strain and method of cultivation)
  • test conditions used, including concentrations used and duration of test
  • results of testing, including:
    • EC50 value
    • no observed effect concentration
    • assessment of time-effect relationship
    • cell concentrations and concentration-effect relationship
    • other observed effects.

Biodegradation

You must provide test results of an assessment of the potential of the chemical to biodegrade in the environment, including the method used and the name of the organisation that conducted the test.

Ready biodegradability (TG 301A-F or equivalent)

This assessment of the ability of the chemical to rapidly biodegrade in the environment is made by studying chemical biodegradation in aqueous solutions over a period of up to 28 days.

You must provide data that includes full details of the method used in the test and tabulation of the time-effect results. For some chemicals not readily biodegradable, you may need to submit data on the inherent and ultimate biodegradability (TG 302A-C or equivalent).

Notes: Although not a scheduled item, it is increasingly common that biodegradation data obtained under anaerobic conditions are available. If so, provide this data, particularly if the notified material is likely to become associated with aquatic sediments. Similarly, provide data on biodegradation in seawater, if available.

Bioaccumulation

You must provide the results of an assessment of the potential of the chemical to bioaccumulate in the environment, both aquatic and terrestrial. A full bioaccumulation test is not a schedule requirement, but results must be provided if available.

The assessment must take into consideration:

  • partition coefficient for n-octanol/water
  • fat solubility
  • water solubility
  • ready biodegradability.

If the chemical has a low partition coefficient and/or is readily biodegradable, then no bioaccumulation testing is required. Refer to the OECD Testing Guidelines on Degradation and Accumulation for more information.

Data provided for Schedule Part C

For all toxicological and eco-toxicological data you must specify the:

  • guidelines being used to conduct the study—if the study was not conducted using a recognised guideline then provide sufficient information about the method used to allow NICNAS to determine if the results obtained are valid
  • raw data generated during testing in  the form of a test report (a summary of results is not sufficient).

The standard of testing to obtain data should conform to the OECD Principles of Good Laboratory Practice.

Last update 30 November 2016