1-Dodecanamine, reaction products with 1,1'-methylenebis[4-isocyanatobenzene] and 1-octanamine

Long-term toxicity to fish

Administrative data

Endpoint:

fish early-life stage toxicity

Type of information:

experimental study planned

Justification for type of information:

TESTING PROPOSAL ON VERTEBRATE ANIMALS

NON-CONFIDENTIAL NAME OF SUBSTANCE:

- Name of the substance on which testing is proposed to be carried out: Reaction mass of 4,4'-methylenediphenyl diisocyanate and Amines, soya alkyl (also known as A003)

- Name of the substance for which the testing proposal will be used [if different from tested substance]:
The substance to be tested has been registered as part of a category approach, therefore the data once generated will be used for the tested substance and will also be included in the dossiers for the following substances:
Reaction product of MDI, Octylamine and Hexamethylenediamine (also known as PU09)
Reaction mass of 4,4'-methylenediphenyl diisocyanate and Amines, soya alkyl (also known as A003)
Polyurea, produced by reacting diphenylmethane diisocyanate with octylamine and dodecyl amine (also known as R03)
Polyurea, produced by reacting diphenylmethane diisocyanate with octyl amine and stearyl amine (also known as R04)

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION [please address all points below]:

- Available GLP studies:
Three short-term fish toxicity studies are available for similar substances (see further details in the ‘Grouping and read across’ section below.
Test item: A mixture of: 3,3'-dicyclohexyl-1,1'-methylenebis(4,1-phenylene)diurea; 3-cyclohexyl-1-(4-(4-(3-octadecylureido)benzyl)phenyl)urea; 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea
RCC. 2005a. Short-term toxicity to fish. SNIF#001-5.1.01-01. RESEARCH AND CONSULTING COMPANY AG 4452 ITINGEN. Guideline: EU Method C.1 (Acute Toxicity for Fish). Results: 24-, 48-, 72- and 96 hours LC50 = > 0.9 mg L-1, 96-hour NOEC = 0.9 mg L-1. Test was conducted at 1000 mg L-1; the water solubility of the substance was recorded as <0.9 mg L-1, and thus an LC50 of > 0.9 mg L-1 should be treated with caution. No mortalities occurred in any of the test vessels, and thus it can be concluded that the substance is not toxic at the limit of its water solubility. Reliability: Klimisch 2; study obtained via an Article 25(3) request.

Test item 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea
RCC. 2005b. Short-term toxicity to fish, SNIF#001-5.1.01-01. RESEARCH AND CONSULTING COMPANY AG 4452 ITINGEN. Guideline: EU Method C.1 (Acute Toxicity for Fish). Results: 24-, 48-, 72- and 96 hours LC50 = > 0.9 mg L-1, 96-hour NOEC = 0.9 mg L-1. Test was conducted at 1000 mg L-1; the water solubility of the substance was recorded as <0.9 mg L-1, and thus an LC50 of > 0.9 mg L-1 should be treated with caution. No mortalities occurred in any of the test vessels, and thus it can be concluded that the substance is not toxic at the limit of its water solubility. Reliability: Klimisch 2; study obtained via an Article 25(3) request.

Test item: N,N''-(methylenedi-4,1-phenylene)bis[N'-octyl]urea
C.I.T. 2005. Short-term toxicity to fish, SNIF#001-5.1.01-01. CENTRE INTERNATIONALDE TOXICOLOGIE (C.I.T.)MISEREY, 27005 EVREUX CEDEX. Guideline: OECD Guideline 203 (Fish, Acute Toxicity Test) and EU Method C.1 (Acute Toxicity for Fish). Results: 24-, 48-, 72- and 96-hour LC50 = > 0.0044 mg L-1, 96-hour LC100 = >0.0044 mg L-1, 96-hour NOEC = =0.0044 mg L-1; all concentrations above the limit of saturation. Reliability: Klimisch 2; study obtained via an Article 25(3) request.

- Available non-GLP studies:
One short-term fish study is available for a similar substance. The data was obtained via an Article 25(3) request, and in the robust study summary provided, the GLP status of the study is not reported.
Test item: 3,3'-dicyclohexyl-1,1'-methylenebis(4,1-phenylene)diurea
Short-term toxicity to fish, SNIF#001-5.1.01-01. Guideline: Not reported. Results: 24-, 48-, 72- and 96 hour LC50 = > 1.0 mg L-1. Reliability: Klimisch 2; study obtained via an Article 25(3) request.

- Historical human data: Not applicable

- (Q)SAR: The ECOSAR Version 1.11 programme (US EPA 2012) has been utilised to provide estimates for representative structures. The model provides estimates according to the class definitions Substituted Ureas and Neutral Organics (baseline toxicity). The Substituted Urea predictions are presented in this testing proposal, which are defined as including the SMILES script NC(=O)N in the SMILES code for the substance. Two representative structures of the substance, representing the highest and lowest molecular weights, were utilised for predictions.

No effects were predicted to be observed at saturation for fish, daphnids or green algae either based on the Log Kow and / or the water solubility cut-off values for two of the representative structures. The predicted Acute (LC50¬, EC50) and Chronic (ChV) effect concentration values were between 3 and 3 x 109 times higher than the solubility of the substance. The QSAR calculations are based on a predicted water solubility and Log Kow, therefore, there is uncertainty associated with the calculation of the derived effect level. Additionally, the chronic ChV value is derived as the geometric mean of the no observed effect concentration (NOEC) and the lowest observed effect concentration (LOEC) (Mayo-Bean et al., 2012), and is considered as supporting information rather than a substitute for chronic test data for this substance.

- In vitro methods: Not applicable

- Weight of evidence: The substance Reaction mass of 4,4’-methylenediphenyl diisocyanate and Amines, soya alkyl (A003) is included in the MDI category. The category has been devised based on substances containing the same core-structure produced using methylene diphenyl diisocyanate (MDI) (further information regarding the category is available in the read-across justification document attached to the IUCLID file). All available data for the MDI category are included in the dossier; however, currently it is deemed to be insufficient to read-across data for all ecotoxicity endpoints in the category, as there is no ecotoxicity data available for the substance Reaction mass of 4,4’-methylenediphenyl diisocyanate and Amines, soya alkyl for comparison with the other category members. Due to the low water solubility of the substance, according to the REACH guidance the long-term aquatic toxicity study on fish should also be considered if the substance is poorly water soluble (ECHA 2017). The current weight of evidence is not considered to be sufficient to fulfil the endpoint requirement without further testing.

- Grouping and read-across: The substance Reaction mass of 4,4’-methylenediphenyl diisocyanate and Amines, soya alkyl is included in a category derived based on substances produced using methylene diphenyl diisocyanate (MDI) and containing the same core-structure. In the current dossier, data for all ecotoxicity endpoints have been read-across from other category members i.e. A mixture of: 3,3'-dicyclohexyl-1,1'-methylenebis(4,1-phenylene)diurea; 3-cyclohexyl-1-(4-(4-(3-octadecylureido)benzyl)phenyl)urea; 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea, 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea and N,N''-(methylenedi-4,1-phenylene)bis[N'-octyl]urea to Reaction mass of 4,4’-methylenediphenyl diisocyanate and Amines, soya alkyl. Following a review of the dossier and categories, and in line with the good dossier guide, a collaboration between CEFIC and ECHA for evaluating, updating and improving REACH registration dossiers, it is proposed that additional testing should be performed to strengthen the read-across based on the ‘Different compounds have the same type of effect(s)’ scenario. To minimise the amount of animal testing to be performed the data on this substance will be read-across to all other category members registered at Annex VIII and above.

- Substance-tailored exposure driven testing [if applicable]: During the commissioning process of the testing the possibility and feasibility of conducting limit tests will be discussed with the selected laboratory.

- Approaches in addition to above [if applicable]: After conducting the study the data will be read-across to other category members registered at Annex VIII and above.

- Other reasons [if applicable]: Due to the poorly soluble nature of the substance, the necessity to consider long-term testing is required, according to ECHA guidance. The substance Reaction mass of 4,4’-methylenediphenyl diisocyanate and Amines, soya alkyl has a geometric mean water solubility of 8.56 x 10-12 mg L-1, based on calculations from four different QSAR programmes (see IUCLID Section 4.8 and associated attachments). Based on this information, and the necessity to assess whether the substance exhibits chronic toxicity at the limit of water solubility, a Fish Early Life-Stage test is proposed.

CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:

- Although the substance is being registered at Annex VIII, the REACH guidance states that “Long-term testing should also be considered if the substance is poorly water soluble.” (ECHA 2017). The substance is poorly water soluble, and therefore conducting an acute fish study as is required at that tonnage band is unlikely to be sufficient to assess any potential toxicity of the test item in the environment. No appropriate data waivers are available for adapting the testing requirement. Read across from a structurally similar substance is currently available for short-term toxicity, however, further evidence is required to confirm a lack of chronic toxicity at the limit of water solubility. Therefore, it is proposed to conduct a Fish Early Life-Stage study to obtain the required information. As this test is an Annex IX study being conducted for an Annex VIII substance, a testing proposal is required.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:

- Details on study design / methodology proposed [if relevant]: The most appropriate method to be followed will be discussed with the CRO during commissioning but is likely to be a Fish Early Life-Stage study following OECD 210 will be conducted. While commissioning the study, if it is deemed acceptable then a limit test will be conducted to reduce the number of organisms used in the study. Due to the poorly soluble nature of the test item, water accommodated fractions may be considered as a suitable way of preparing the test solutions.

References:
C.I.T. 2005. Short-term toxicity to fish, SNIF#001-5.1.01-01. CENTRE INTERNATIONALDE TOXICOLOGIE (C.I.T.)MISEREY, 27005 EVREUX CEDEX.

ECHA. 2017. Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7b: Endpoint specific guidance, Version 4.0. European Chemicals Agency. DOI: 10.2823/84188.

Mayo-Bean K, Moran K, Meylan B, Ranslow P. 2012. Methodology Document for the ECOlogical Structure-Activity Relationship Model (ECOSAR) Class Program; Estimating Toxicity of Industrial Chemicals to Aquatic Organisms using the ECOSAR (Ecological Structure Activity Relationship) Class Program. U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., N.W., Washington, DC 20460.

RCC. 2005a. Short-term toxicity to fish. SNIF#001-5.1.01-01. RESEARCH AND CONSULTING COMPANY AG 4452 ITINGEN.

RCC. 2005b. Short-term toxicity to fish, SNIF#001-5.1.01-01. RESEARCH AND CONSULTING COMPANY AG 4452 ITINGEN

[US EPA] U.S. Environmental Protection Agency. 2012. ECOSAR v1.11. The ECOSAR (ECOlogical Structure Activity Relationship Class Program for Microsoft Windows. Office of Chemical Safety and Pollution Prevention, U.S. Environmental Protection Agency.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 210 (Fish, Early-Life Stage Toxicity Test)

Test material

Test material information

Constituent 1