Guidelines for the Notification and Testing of New Substances: Chemicals and Polymers

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APPENDIX 8 - Examples of Waiver Conditions

1. 1.0 Physical and Chemical Data
   1. 1.1 Examples of Justifications
      1. 1.1.1 Density
      2. 1.1.2 Vapour Pressure
      3. 1.1.3 Water Solublility
      4. 1.1.4 Partition Coefficient
      5. 1.1.5 Adsorption-Desorption
      6. 1.1.6 Hydrolysis as a Function of pH (Screening Portion)
      7. 1.1.7 Number-average Molecular Weight
      8. 1.1.8 Concentration of Residual Constituents
      9. 1.1.9 Ultraviolet-Visible Spectrum
2. 2.0 Ecotoxicological Data
3. 3.0 Health Toxicity Data
   1. 3.1 Examples of Justifications
      1. 3.1.1 Acute Toxicity (Oral, Dermal, or Inhalation)
      2. 3.1.2 Repeated Dose Toxicity (Oral, Dermal, or Inhalation)
      3. 3.1.3 Skin Irritation
      4. 3.1.4 Skin Sensitization
      5. 3.1.5 In Vitro Gene Mutation
      6. 3.1.6 In Vitro Mammalian Chromosomal Abberation
      7. 3.1.7 In Vivo Mammalian Mutagenicity

The requirement to provide test data on a chemical or polymer may be waived if sufficient justification is given. Examples of conditions under which waivers may be granted by the Minister are described below. These and other conditions for accepting a waiver of information will be considered on a case-by-case basis.

1.0 Physical and Chemical Data

Generally applicable:

a) if the chemical properties or physical form of the substance preclude(s) the adequate conduct of the test. The rationale should provide sound reasoning as to why it is not technically feasible or practicable to conduct the test; and

b) if the substance cannot be isolated from the reaction medium in which it is formed and information generated on the mixture would not be meaningful for the assessment of the notified substance. Information documenting efforts to isolate the substance should be provided.

1.1 Examples of Justifications

1.1.1 Density

The substance is only stable in solution in a particular solvent and the solution density is similar to that of the solvent. In such cases, an indication of whether the solution density is higher or lower than the solvent density would be sufficient.

1.1.2 Vapour Pressure

The substance is unstable in the purified form.

1.1.3 Water Solublility

1. The substance reacts dangerously with water (e.g., liberates a poisonous gas).
2. The substance is highly volatile; therefore, determination of water solubility is not technically feasible.
3. The substance forms a stable emulsion in water which cannot be separated by filtration or centrifugation methods.

1.1.4 Partition Coefficient

1. The substance decomposes or reacts dangerously during the performance of the test.
2. The substance is surface active.

1.1.5 Adsorption-Desorption

1. The solubility of the substance in water cannot be measured analytically; therefore, determination of adsorption is not technically feasible.
2. The substance decomposes (e.g., biodegradation or hydrolysis) or reacts dangerously during the performance of the test.

1.1.6 Hydrolysis as a Function of pH (Screening Portion)

1. The substance reacts dangerously with water.
2. The substance is a member of one or more of these groups and does not contain other functional groups that could change the hydrolysis potential of the substance:

   Alcohols	Glycols
   Aldehydes	Halogenated aromatics
   Alkanes	Heterocyclic polycyclic aromatic hydrocarbons
   Alkenes	Hydrocarbons
   Alkynes	Ketones
   Aromatic amines	Phenols
   Aromatic nitro compounds	Polycyclic aromatic hydrocarbons
   Benzenes/Biphenyls	Sulphonic acids
   Carboxylic acids	Ethers

3. The substance has no readily hydrolysable groups and therefore is not expected to hydrolyze.

1.1.7 Number-average Molecular Weight

The polymer cannot be dissolved in any solvent suitable for use in an analytical method. Information documenting the efforts to dissolve the polymer should be provided. If the polymer is soluble at >2%, a GPC should be performed and provided on the soluble portion of the polymer.

1.1.8 Concentration of Residual Constituents

1. The polymer cannot be dissolved in any solvent suitable for use in an analytical method. Information documenting the efforts to dissolve the polymer should be provided.
2. A residual constituent of the substance cannot be measured analytically; therefore, determination of its concentration is not technically feasible.

1.1.9 Ultraviolet-Visible Spectrum

The substance is explosive or reacts dangerously in the presence of light.

2.0 Ecotoxicological Data

The chemical properties or physical form of the substance preclude(s) the adequate conduct of the test. The rationale should provide sound reasoning as to why it is not technically feasible or practicable to conduct the test.

3.0 Health Toxicity Data

Generally applicable:

1. if the chemical properties or physical form of the substance preclude(s) the adequate conduct of the test. The rationale should provide sound reasoning as to why it is not technically feasible or practicable to conduct the test;
2. if the substance cannot be isolated from the reaction medium in which it is formed, and information generated on the mixture would not be meaningful for the assessment of the notified substance. Information documenting efforts to isolate the substance should be provided;
3. if the polymer does not meet the criteria for a reduced regulatory requirement polymer solely due to the presence of the following cationic or potentially cationic groups: primary, secondary, tertiary amine groups, carbodiimides or sulphoniums. Cationic groups not specified above, including quarternary amines, hindered amines, azides, isocyanates (free and blocked) and phosphoniums will generally not be eligible for waivers of all toxicological test requirements. They may, however, be considered for waivers of certain requirements on a case-by-case basis. Polymers with an M_n of greater than 10 000 daltons will generally not be eligible for a waiver of acute and repeated dose toxicity tests if inhalation is expected to be the most significant route of exposure of the general population based on expected type of use; and
4. if the polymer does not contain greater than 0.1% species having molecular weight less than 1000 daltons and available information (e.g., potential hydrolysis, biodegradation, toxicity) indicates that the polymer does not readily break down, and will not be biologically available.

3.1 Examples of Justifications

3.1.1 Acute Toxicity (Oral, Dermal, or Inhalation)

1. The substance is corrosive or highly irritating, or is expected to be corrosive or highly irritating based on consideration of factors such as pH and chemical reactivity; therefore, administration of the substance in accordance with the test protocol for the acute toxicity test would cause severe and enduring pain to the test animals.
2. It is not technically feasible to administer known doses of the substance because of its chemical or physical properties (e.g., the substance is a gas that cannot be dissolved to a detectable level into an appropriate oral vehicle).

3.1.2 Repeated Dose Toxicity (Oral, Dermal, or Inhalation)

It is not technically feasible to administer known doses of the substance because of its chemical or physical properties.

3.1.3 Skin Irritation

1. It is not technically feasible to administer the substance topically.
2. The substance has demonstrated high acute dermal toxicity; therefore, administration of the substance in accordance with the test protocol for skin irritation would cause excessive animal deaths (e.g., >25%).

3.1.4 Skin Sensitization

1. It is not technically feasible to administer the substance topically.
2. The substance is corrosive or highly irritating; therefore, administration of the substance in accordance with the test protocol for skin sensitization would cause severe and enduring pain to the test animals, and/ or obscure any skin sensitization reaction.

3.1.5 In Vitro Gene Mutation

1. An in vitro mammalian chromosomal aberration assay indicates that the substance has mutagenic activity.
2. An in vivo mammalian genotoxicity assay indicates that the substance has mutagenic activity.

3.1.6 In Vitro Mammalian Chromosomal Abberation

1. An in vitro gene mutation assay indicates that the substance has mutagenic activity.
2. An in vivo mammalian genotoxicity test indicates that the substance has mutagenic activity.

3.1.7 In Vivo Mammalian Mutagenicity

1. The results of both the in vitro gene mutation and the in vitro mammalian chromosomal aberration tests indicate that the substance has no mutagenic activity in those tests.
2. The intended use of the substance will not involve direct, repeated, or prolonged human exposure.
3. The chemical structure of the substance, or part thereof, is not related to a known mutagen or carcinogen.