2,4,6-triisopropyl-m-phenylene diisocyanate

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2020 August - 2020 September

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Due to quick hydrolysis (see cross-reference), the study is performed with TRIDA in accordance with RAAF Scenario 1 (ECHA 2017).

Reason / purpose:

read-across: supporting information

Qualifier:

according to

Guideline:

OECD Guideline 305 (Bioaccumulation in Fish: Aqueous and Dietary Exposure) -I: Aqueous Exposure Bioconcentration Fish Test

Deviations:

not applicable

Remarks:

study ongoing

GLP compliance:

yes (incl. certificate)

Radiolabelling:

no

Vehicle:

no

Details on preparation of test solutions, spiked fish food or sediment:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: The stock solution and the test water will be pumped into a mixing vessel (one per replicate) with a constant flow rate. In these vessels the stock solutions and the test water will be continuously mixed using a magnetic stirrer. A nominal test concentration of 500 µg/L will result. The mixing vessels and the aquaria will be connected by a tube.
Prior to the initiation of the test the dosing system will be calibrated through the use of appropriate analysis techniques (non-GLP).
- Control: test water only

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Details on test organisms:

TEST ORGANISM
- Common name: Rainbow trout (Oncorhynchus mykiss)
- Source: The test fish will be obtained from a commercial fish breeder given in the final report.
- Age at study initiation (mean and range, SD): juvenile
- Feeding during test
- Food type: A commercially available fish food (floating and/or slow sinking pelletized diet) that is characterised in terms of at least protein and fat content will be used.
Initial feeding will be based on the scheduled weight measurements of the stock population just prior to the start of the test. The amount of feed will be adjusted based on the wet weights of sampled fish at each sampling event to account for growth during the experiment.
- Amount: approximately 1 to 2% of body weight per day
- Frequency: The fish will be fed daily throughout the test periods.

ACCLIMATION
- Acclimation period: After arrival, the stock population of fish will be acclimated for at least two weeks.
- Acclimation conditions (same as test or not): After arrival, the stock population of fish will be acclimated in water at the test temperature. Both water and diet will be of the same type as those to be used during the test.
- Type and amount of food: A commercially available fish food (floating and/or slow sinking pelletized diet) that is characterised in terms of at least protein and fat content will be used. The fish will be fed at a level of approximately 1 to 2% of body weight per day.
- Feeding frequency: The fish will be fed daily throughout the test periods.
- Health during acclimation (any mortality observed): The mortality will be recorded. A batch mortality <5% in preceding 7 days after receipt is considered acceptable. If mortalities between 5 and 10% of the population in seven days occur, the batch will be acclimated for seven additional days. If more than 5% mortality during the second seven days will be observed, the entire batch will be rejected. In case of mortality exceeding 10% of the population in seven days, the batch will not be used for the test.

Route of exposure:

aqueous

Justification for method:

aqueous exposure method used for following reason: water solubilty 1.1 mg/L and log Kow < 4

Test type:

semi-static

Water / sediment media type:

natural water: freshwater

Total exposure / uptake duration:

>= 7 - <= 28 d

Total depuration duration:

<= 56 d

Hardness:

2.5 mmol/L (= 250 mg/L) as CaCO3

Test temperature:

13-17°C, within a range of ± 2°C

pH:

In a range of 6.0 to 8.5 at test start (during the test the pH should be within a range of ± 0.5 pH units)

Dissolved oxygen:

At least 60% of the saturation value

Details on test conditions:

TEST SYSTEM
- Test vessel: Glass aquaria
- Type (delete if not applicable): open
- Material, size, headspace, fill volume: approx. 40 litres test medium
- Type of flow-through (e.g. peristaltic or proportional diluter): Exchange of test media at least five fold per day.
- Renewal rate of test solution (frequency/flow rate):
- No. of organisms per vessel: 85 per control and test item group
- No. of vessels per concentration (replicates): 1
- No. of vessels per control / vehicle control (replicates): 1
- Biomass loading rate: Addition of the fish should result in a fish-to-water loading rate of 0.1-1.0 g of fish (wet weight) per litre of water per day.
- Other: The test is conducted in a controlled environment room, in a ventilated area.

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Reconstituted water will be used in the test. The detailed composition is given in section "Any other information on materials and methods incl. tables".

OTHER TEST CONDITIONS
- Photoperiod: 16 h light : 8 h dark
- Light intensity: 400 to 800 lux

Nominal and measured concentrations:

nominal: 500 µg/L and a control

Reference substance (positive control):

no

Remarks on result:

not measured/tested

Remarks:

Study ongoing

Remarks on result:

not measured/tested

Remarks:

Study ongoing

Remarks on result:

not measured/tested

Remarks:

Study ongoing

Remarks on result:

not measured/tested

Remarks:

Study ongoing

Validity criteria fulfilled:

not applicable

Remarks:

Study ongoing

Conclusions:

The study is running under GLP according to OECD TG 305-I on the registered substance itself. The method is to be considered scientifically reasonable and no deficiencies in documentation or deviations from the guidelines are expected. Hence, the outstanding results can be considered as reliable to assess the bioaccumulation potential of the test substance towards fish. Currently outstanding results and additional relevant study data will be added to complete the study record as soon as the final report is available.

Reference 2

Endpoint:

bioaccumulation in aquatic species: fish

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reference 3

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

12 June 2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
Estimation Programs Interface (EPI) Suite for Microsoft Windows, v4.11 (US EPA, 2012)

2. MODEL (incl. version number)
BCFBAF v3.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC(C)c1cc(C(C)C)c(N=C=O)c(C(C)C)c1N=C=O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRF.

6. ADEQUACY OF THE RESULT
- The model is scientifically valid (see attached QMRF).
- See attached QPRF for reliability assessment.

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

- Software tool(s) used including version: EpiSuite v4.11
- Model(s) used: BCFBAF v3.01
- Model description: see field ''Attached justification'
- Justification of QSAR prediction: see field 'Attached justification'

Specific details on test material used for the study:

CC(C)c1cc(C(C)C)c(N=C=O)c(C(C)C)c1N=C=O

Test organisms (species):

other: Fish, not further specified

Test type:

other: QSAR

Water / sediment media type:

natural water: freshwater

Details on estimation of bioconcentration:

Using the computer tool BCFBAFWIN v3.01 by US-EPA (EPIWIN) the Bioconcentration Factor (BCF) can be estimated. The following two different models are used: Regression-based estimate (Traditional method), based on WSKOWWIN and Arnot-Gobas method, based on mechanistic first principles.

Type:

BCF

Value:

7 065 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Regression-based estimate (Traditional Method), based on WSKOWWIN

Type:

BCF

Value:

5 970 L/kg

Basis:

whole body w.w.

Remarks on result:

other: Arnot-Gobas method, based on mechanistic first principles

Details on results:

Prediction of apparent metabolism half-life in fish:
Arnot-Gobas method, upper trophic: 152.8 L/kg wet-wt
Arnot-Gobas method, mid trophic: 210.5 L/kg wet-wt
Arnot-Gobas method, lower trophic: 232.2 L/kg wet-wt

Validity criteria fulfilled:

yes

Remarks:

scientifically accepted calculation method

Conclusions:

The study report describes a scientifically accepted calculation method for the bioconcentration factor estimation using the US-EPA software BCFBAF v3.01. No GLP criteria are applicable for the usage of this tool and the QSAR estimation is easily repeatable. Using the regression-based estimate (traditional method) a BCF of 7065 L/kg wet-wt was calculated. Using the Arnot-Gobas method, which is based on the mechanistic first principles, the BCF results in a value of 5970 L/kg wet-wt. The whole body primary biotransformation rate estimate for fish gives a half-life of 3.214 days, whereby the rate constant (kM) for 10 g fish is designated as 0.2157/day. This is taken into account to predict the apparent metabolism half-life in fish for the substance. For the lower trophic level a BCF of 232.2 L/kg wet-wt is calculated, whereas for the mid trophic level the BCF will result in 210.5 L/kg wet-wt and the higher trophic level gives a value of 152.8 L/kg wet-wt.

Executive summary:

The prediction for the bioconcentration factor (BCF) of the substance 2,4,6 -triisopropyl-m-phenylene diisocyanate was determined by the computer program BCFBAF v3.01 (EPIWIN software) by US-EPA (2012). Furthermore the whole body primary biotransformation rate estimation for fish was calculated with the notation that the bio half-life normalized to 10 g fish at 15 °C. It is possible to predict the apparent metabolism half-life in fish for three different trophic levels (lower, mid and upper). Using the regression-based estimate (traditional method) a BCF of 7065 L/kg wet-wt was calculated. Using the Arnot-Gobas method, which is based on the mechanistic first principles, the BCF results in a value of 5970 L/kg wet-wt. The whole body primary biotransformation rate estimate for fish gives a half-life of 3.214 days, whereby the rate constant (kM) for 10 g fish is designated as 0.2157/day. This is taken into account to predict the apparent metabolism half-life in fish for the substance. For the lower trophic level a BCF of 232.2 L/kg wet-wt is calculated, whereas for the mid trophic level the BCF will result in 210.5 L/kg wet-wt and the higher trophic level gives a value of 152.8 L/kg wet-wt.

Description of key information

1) Key_Bioaccumulation aquatic / sediment:

2) Waiver_Bioaccumulation: aquatic / sediment: According to REACH Regulation (EC) No 1907/2006 Article 2 (9), polymers are excluded from Titles II (Registration) and VI (Evaluation).

3) Supporting_Bioaccumulation: aquatic / sediment_QSAR: BCFBAF v3.01 (EPISuite v4.11, US EPA 2012), BCF = 7065 L/kg ww

Additional information

Due to the very fast hydrolysis (DT50 = 37s) hydrolysis and the resulting instability of the test substance, it was considered most meaningful to cover the information on the bioaccumulative potential by the consideration of the degradation products. Based on the results of the hydrolysis study conducted at CURRENTA GmbH according to OECD 111,2,4,6-triisopropyl-m-phenylene diamine (TRIDA, CAS 6318-09-08) was expected as major hydrolysis and polymeric ureas as potential minor hydrolysis products (Neuland, 2020).

A study with 2,4,6-triisopropyl-m-phenylene diamine (TRIDA) according to OECD TG 305-I /Aqueous Exposure) is currently running at ibacon GmbH, which is presented as key study. Therefore, no final results on the bioaccumulative potential of TRIDA as major hydrolysis product can be presented so far but will be added as soon as the final report is available .

The determination of the bioaccumulative potential of the polyureas as minor hydrolysis product is waived, as polymers are exempted from registration and evaluation under REACH.

As supporting information the bioconcentration factor (BCF) of the test substance was determined by the computer program BCFBAF v3.01 (EPIWIN software) by US-EPA (2012). Furthermore the whole body primary biotransformation rate estimation for fish was calculated with the notation that the bio half-life normalized to 10 g fish at 15 °C. It is possible to predict the apparent metabolism half-life in fish for three different trophic levels (lower, mid and upper). Using the regression-based estimate (traditional method) a BCF of 7065 L/kg wet-wt was calculated. Using the Arnot-Gobas method, which is based on the mechanistic first principles, the BCF results in a value of 5970 L/kg wet-wt. The whole body primary biotransformation rate estimate for fish gives a half-life of 3.214 days, whereby the rate constant (kM) for 10 g fish is designated as 0.2157/day. This is taken into account to predict the apparent metabolism half-life in fish for the substance. For the lower trophic level a BCF of 232.2 L/kg wet-wt is calculated, whereas for the mid trophic level the BCF will result in 210.5 L/kg wet-wt and the higher trophic level gives a value of 152.8 L/kg wet-wt. No GLP criteria are applicable for the usage of this tool, but due to the fact that it is a scientifically accepted calculation method the estimations performed are reliable with restrictions.