Reaction products of 2- and 4-methyl-m-phenylene diisocyanate with C16-18-(even numbered, C18-unsaturated)-alkylamines and ethylenediamine

Long-term toxicity to aquatic invertebrates

Administrative data

Endpoint:

long-term toxicity to aquatic invertebrates

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: Polyurea, produced by reacting toluene diisocyanate with octyl amine and tallow alkyl amines (also known as R37 and Diurea 8)

- 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 (Polyurea, produced by reacting toluene diisocyanate with octyl amine and tallow alkyl amines) and will also be included in the dossiers for the following substances:
N,N''-ethylenebis[N'-[2-methyl-5-[[(octadecylamino)carbonyl]amino]phenyl]urea] (also known as R61 / A055; new name of Reaction products of 2- and 4-methyl-m-phenylene diisocyanate with C16-18-(even numbered, C18-unsaturated)-alkylamines and ethylenediamine)
Reaction product of m-tolylidene diisocyanate and cyclohexylamine and cyclohex-1,2-ylenediamine and (Z)-octadec-9-enylamine (also known as R60b / PU20)
Reaction product of TDI, p-toluidine and Octylamine (also known as PU06)
Polyurea, produced by reacting toluene diisocyanate with 1, 6-diaminohexane and tallow alkyl amines (also known as R38)

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:
A GLP short-term Daphnia toxicity study is available for the substance in grease base to be tested:
Goodband TJ. 2011a. Diurea thickener 8 base grease: ACUTE TOXICITY TO DAPHNIA MAGNA. Report Number: 41101773. Harlan Laboratories Ltd Shardlow Business Park Shardlow Derbyshire DE72 2GD UK. Guideline: OECD 202 and EU Method C.2. Results: 48-hour EL50 based on immobilisation = > 100 mg L-1, 48-hour NOELR based on immobilisation = ≥100 mg L-1. Reliability: Klimisch 1.

In addition, GLP acute studies with Daphnia magna are also available for two other members of the category (see further details in the ‘Grouping and read across’ section below).
Test item Reaction product of m-tolylidene diisocyanate and cyclohexylamine and cyclohex-1,2-ylenediamine and (Z)-octadec-9-enylamine (R60b/PU20):
Kley A and Wydra V. 2010. Acute Toxicity of Urea Thickener TOCD to Daphnia magna in a Static 48-hour Immobilisation Limit Test. Study Number: 50583220. Institut für Biologische Analytik und Consulting IBACON GmbH, Arheilger Weg 17, 64380 Rossdorf, Germany. Guideline: OECD 202 and EU Method C.2. Results: 24- and 48-hour EC50 based on immobilisation = > 100 mg L-1, 24- and 48-hour NOEC based on immobilisation = ≥100 mg L-1. Reliability: Klimisch 1.

Test item: Tetraurea grease 2:
Goodband TJ. 2011b. ACUTE TOXICITY TO DAPHNIA MAGNA. Report Number: 41101769. Harlan Laboratories Ltd Shardlow Business Park Shardlow Derbyshire DE72 2GD UK. Guideline: OECD 202 and EU Method C.2. Results: 48-hour EL50 based on immobilisation = > 100 mg L-1, 48-hour NOELR based on immobilisation = ≥100 mg L-1. Reliability: Klimisch 1.

- Available non-GLP studies: Currently no non-GLP studies are available.

- 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. Three 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 1.5 and >1000 times higher than the solubility of the substance. For one representative structure, effects were predicted for Daphnia for both chronic and acute effects, and for chronic effects on fish, at levels below the limit of solubility for the substance. Additionally, the predicted Log Kow was also below the threshold for no chronic effects at saturation (Log Kow = 8). 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; currently no appropriate in vitro methods are available.

- Weight of evidence: The substance Polyurea, produced by reacting toluene diisocyanate with octyl amine and tallow alkyl amines (R37) is included in the TDI-I category. The category has been devised based on substances containing the same core-structure produced using toluene diisocyanate (TDI) and with straight-chain end groups (further information regarding the category is available in the read-across justification document attached to the IUCLID file). All available data for the TDI-I category are included in the dossier. However, the data requirement regarding long-term toxicity to Daphnia is currently waived in the dossier. The adaptation used is based on the Annex IX column 2 adaptation “9.1 Long-term toxicity testing shall be proposed by the registrant if the chemical safety assessment according to Annex I indicates the need to investigate further the effects on aquatic organisms.” As long-term data are not currently available, it is proposed that a Daphnia reproduction study is performed to fulfil the Annex IX data requirement for R37. 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 Polyurea, produced by reacting toluene diisocyanate with octyl amine and tallow alkyl amines is included in a category derived based on substances produced using toluene diisocyanate (TDI) and containing the same core-structure and straight-chain end groups (further information regarding the category is available in the read-across justification document attached to the IUCLID file). In the current dossier, data for ecotoxicity endpoints for other category members, i.e. Reaction product of m-tolylidene diisocyanate and cyclohexylamine and cyclohex-1,2-ylenediamine and (Z)-octadec-9-enylamine and Tetraurea Grease 2 (as detailed above), have been read-across to Polyurea, produced by reacting toluene diisocyanate with octyl amine and tallow alkyl amines. There are also some data available for the registered substance itself, i.e. Goodband (2011a and 2011b) and Vryenhoef (2011). Following a review of the dossier and category, and in line with the REACH Dossier Improvement Action Plan - a collaboration between Cefic and ECHA for evaluating, updating and improving REACH registration dossiers - a Daphnia reproduction study is proposed to be performed as this is an Annex IX data requirement as there is currently no chronic ecotoxicity data available in the category.

- 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 used to justify the read-across of ecotoxicity data for other endpoints between category members, as well as to complete the Annex IX data requirement for the test substance.

- Other reasons [if applicable]: There is a necessity to consider long-term toxicity of the substance due to the substance being registered at Annex IX, according to the REACH information requirements. The substance Polyurea, produced by reacting toluene diisocyanate with octyl amine and tallow alkyl amines has a geometric mean water solubility of 0.0067 mg L-1, based on calculations from four different QSAR programmes (Dawick 2009). Based on this information, and the necessity to assess whether the substance exhibits chronic toxicity at the limit of water solubility, a Daphnia reproduction 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:

- The substance is registered at Annex IX, and currently the long-term aquatic toxicity study with Daphnia has been waived due to exposure considerations. However, this endpoint is a standard Annex IX requirement. As the dossier does not currently include chronic ecotoxicity data, it is therefore believed that conducting a Daphnia reproduction study following the OECD 211 guideline will fulfil the data requirement for this substance and provide additional supporting information for the category.

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

- Details on study design / methodology proposed [if relevant]: A Daphnia reproduction study following the OECD 211 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:

Dawick J. Shell Diurea 8 Grease Thickener: In Silico Prediction of Physicochemical Properties. SHELL INTERNATIONAL B.V., THE HAGUE.

Goodband TJ. 2011a. Diurea thickener 8 base grease: ACUTE TOXICITY TO DAPHNIA MAGNA. Report Number: 41101773. Harlan Laboratories Ltd Shardlow Business Park Shardlow Derbyshire DE72 2GD UK.

Goodband TJ. 2011b. ACUTE TOXICITY TO DAPHNIA MAGNA. Report Number: 41101769. Harlan Laboratories Ltd Shardlow Business Park Shardlow Derbyshire DE72 2GD UK.

Kley A and Wydra V. 2010. Acute Toxicity of Urea Thickener TOCD to Daphnia magna in a Static 48-hour Immobilisation Limit Test. Study Number: 50583220. Institut für Biologische Analytik und Consulting IBACON GmbH, Arheilger Weg 17, 64380 Rossdorf, Germany.

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.

[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.
Vryenhoef H. 2011. Algal Growth Inhibition Test. Report Number: 41101774. Harlan Laboratories Ltd Shardlow Business Park Shardlow Derbyshire DE72 2GD UK.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 211 (Daphnia magna Reproduction Test)

Test material

Test material information

Constituent 1

Reference substance name:

Polyurea, produced by reacting toluene diisocyanate with octyl amine and tallow alkyl amines

Cas Number:

1312943-30-8

Molecular formula:

The predominant chemical structures, their respective molecular weight (MW), abbreviated chemical name and molecular formula are given in structural formula image.

IUPAC Name:

Polyurea, produced by reacting toluene diisocyanate with octyl amine and tallow alkyl amines