bis(2-ethylhexyl) 4,4’-{6-[4-tert-butylcarbamoyl)anilino]-1,3,5-triazine-2,4-diyldiimino}dibenzoate

Bioaccumulation: aquatic / sediment

Administrative data

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

February 2, 2022

Reliability:

1 (reliable without restriction)

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
EPIWEB v4.1

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

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES : CCCCC(CC)COC(=O)c1ccc(cc1)Nc2nc(Nc3ccc(cc3)C(=O)OCC(CC)CCCC)nc(Nc4ccc(cc4)C(=O)NC(C)(C)C)n2
Experimental Log Kow (octanol-water): 4.12
Experimental Water Solubility (mg/L): 0.00075
Experimental Vapor Pressure (mm Hg) : 1.43E-006
Experimental Melting Point (deg C) : 89.85



4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: bioconcentration factor (BCF; L/kg) and bioaccumulation factor (BAF; L/kg)

- Unambiguous algorithm: For the BCF calculation the following equation was used - Log BCF  =  0.6598 Log Kow  -  0.333  + Σ correction factors (n = 396, r2 = 0.792, Q2 = 0.78, std dev = 0.511, avg dev = 0.395)

For the BAF calculation, the following method was used - Arnot JA, Gobas FAPC. 2003. A generic QSAR for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. QSAR and Combinatorial Science 22: 337-345.

- Defined domain of applicability: non-ionic organic chemicals with MW between 68.08 - 959.17 and Log Kow of -6.50 to 11.26
- Appropriate measures of goodness-of-fit and robustness and predictivity: A detailed discussion of estimation accuracy is found in the BCFBAF help file (attached).
- Mechanistic interpretation: The Arnot-Gobas model includes mechanistic processes for bioconcentration and bioaccumulation such as chemical uptake from the water at the gill surface (BCFs and BAFs) and the diet (BAFs only), and chemical elimination at the gill surface, fecal egestion, growth dilution and metabolic biotransformation. It also includes bioavailability in the water column (only the freely dissolved fraction can bioconcentrate) and absorption efficiencies at the gill and in the gastrointestinal tract.

5. APPLICABILITY DOMAIN
- Descriptor domain: lower, middle and upper trophic levels in fish in temperate environments
- Structural domain: The model was derived using a training set of 466 non-ionic organic compounds, and 61 ionic organic compounds.
- Mechanistic domain: A discussion of the model domain can be found in the BCFBAF help file (attached).
- Similarity with analogues in the training set: The training set included substances with aromatic sym-triazine rings, and alkyl chains with 8+ CH2 groups.
- Other considerations (as appropriate):

6. ADEQUACY OF THE RESULT
The purpose of this modelling effort is to complete the requirements of a REACH registration dossier.
Approach for regulatory interpretation of the model result: The results will inform the nature of potential exposure of the substance to humans and other organisms.
The results of the modelling effort concludes that the subject chemical UVASORB HEB is sparingly soluble in water and is expected to exhibit very low bioavailability to aquatic and soil organisms.
Conclusion: These results are adequate for prediction of the bioaccumulation and bioavailability of the substance.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to other study

Reference

Endpoint:

vapour pressure

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 104 (Vapour Pressure Curve)

Qualifier:

according to guideline

Guideline:

EU Method A.4 (Vapour Pressure)

GLP compliance:

yes (incl. QA statement)

Type of method:

effusion method: vapour pressure balance

Temp.:

25 °C

Vapour pressure:

< 0 Pa

No statistical analyses were performed because the balance readings were too low and variable for a line of best fit to have any meaning. Instead it was considered more appropriate to impose a regression slope on a chosen data point to provide an estimate of the maximum value for the vapour pressure at 25°C.

The value of -1500K is an in-house value and is the shallowest slope observed whilst determining the vapoure pressure on a wide range of samples using the vapour pressure balance method. Extrapolation to 25°C gave a vapour pressure of 1.852*10^-4 Pa which has been taken as a maximum for this material.

Conclusions:

The vapour pressure of the test material has been determined to be less than 1.9*10^-4 Pa at 25°C

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

GLP compliance:

yes (incl. QA statement)

Type of method:

column elution method

Water solubility:

< 0 g/L

Temp.:

20 °C

pH:

>= 5.4 - <= 7.1

Conclusions:

The water solubility of the test material has been determined to be less than 7.50*10^-7 g/L of solution at 20.0+/-0.5°C

Cross-reference 3

Reason / purpose for cross-reference:

reference to other study

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

GLP compliance:

not specified

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

4.12

Temp.:

20 °C

pH:

6.2

Test no. P log Pow

1A 23110 4.36

1B 19610 4.29

2A 9448 3.97

2B 8011 3.90

3A 12241 4.09

3B 12662 4.10

From the values elaboration a mean value of log Pow 4.12 with a standard deviation of 0.20 is obtained.

The pH of the aqueous phase was identical as distilled water used in the tests.

Conclusions:

From the values elaboration a mean value of log Pow 4.12 with a standard deviation of 0.20 is obtained.

Cross-reference 4

Reason / purpose for cross-reference:

reference to other study

Reference

Endpoint:

melting point/freezing point

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

EU Method A.1 (Melting / Freezing Temperature)

GLP compliance:

not specified

Type of method:

capillary method

Melting / freezing pt.:

> 88.3 - < 91.4 °C

4 measurations are provided the following results:

I = 90.4°C

II = 88.3°C

III = 91.4°C

IV = 90.5°C

These values were confirmed by the microscopic of fusion

method.

The observed temperature range was 88 -90 °C.

Conclusions:

The range of melting of the sample is 88.3 - 91.4°C, match 361.4 - 364.5 K

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2022

Report date:

2022

Materials and methods

Principles of method if other than guideline:

- Software tool(s) used including version: EPIWEB v4.1
- Model(s) used: BCFBAF v3.01
- Model description: see field 'Justification for type of information'
- Justification of QSAR prediction: see field 'Justification for type of information'

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

421-450-8

EC Name:

-

Cas Number:

154702-15-5

Molecular formula:

C44H59N7O5

IUPAC Name:

2-ethylhexyl 4-[(4-{[4-(tert-butylcarbamoyl)phenyl]amino}-6-[(4-{[(2-ethylhexyl)oxy]carbonyl}phenyl)amino]-1,3,5-triazin-2-yl)amino]benzoate

Results and discussion

Bioaccumulation factor

Bioaccumulation factor 1

Key result

Temp.:

10 °C

Type:

BAF

Value:

12.5 L/kg

Basis:

whole body w.w.

Bioaccumulation factor 2

Key result

Type:

BCF

Value:

3.12 L/kg

Basis:

whole body w.w.

Applicant's summary and conclusion

Conclusions:

The bioconcentration factor (BCF) is 3.12 L/kg based on QSAR modeling, and the bioaccumulation factor is (BAF) is 12.5 L/kg based on modeling.

Executive summary:

UVASORB HEB is sparingly soluble in water and is expected to exhibit very low bioavailability to aquatic and soil organisms because of its high affinity towards particulate and organic carbon phases in soil and water.

The log Kow value is 4.12 and from REACH R11, for organic substances with a log Kow value below 4.5 it is assumed that the affinity for the lipids is insufficient to exceed the B criterion, i.e. a BCF value of 2000 L/kg (based on wet weight of the organism, which refers to fish in most cases).

With the use of the EPAs predictive model BCFBAF v. 3.00 (within EPIWEB v. 4.1, US EPA, 2012), a bioconcentration factor (BCF) of 3.162 L/kg wet-wt is estimated with the upper trophic BCF and BAF both estimated to be 12.54.