A mixture of: isomers of 2-(2H-benzotriazol-2-yl)-4-methyl-(n)-dodecylphenol; isomers of 2-(2H-benzotriazol-2-yl)-4-methyl-(n)-tetracosylphenol; isomers of 2-(2H-benzotriazol-2-yl)-4-methyl-5,6-didodecyl-phenol. n=5 or 6

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species: fish

Remarks:

The BCF values for the identified metabolites from the OECD 308 study (see chapter 5.2.2 for details) were modeled.

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
OASIS Catalogic v5.14.1.5

2. MODEL (incl. version number)
BCF base-line model v04.11 - November, 2019

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See section 'Test Material'.

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).
- The model estimates the Bioconcentration factor (BCF) as required information point according to Regulation (EC) No 1907/2006 [REACH], Annex IX, 9.3.2 Bioaccumulation in aquatic species (preferably fish);
further related predictions: Apparent effect of mitigating factors / Maximum bioconcentration factor (BCFmax) / Maximum diameter of energetically stable conformers / Whole body primary biotransformation half-life / Metabolic biotransformation rate constant Km / Metabolites and their quantitative distribution
- See attached QPRF for reliability assessment.

Principles of method if other than guideline:

Calculation using Catalogic v.5.14.1.5, BCF base-line model v.04.11

GLP compliance:

no

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: OASIS Catalogic v5.14.1.5 [BCF base line model - v.04.11]

Key result

Type:

BCF

Value:

2.69 - 4.9 L/kg

Remarks on result:

other: BCF corrected (considering all mitigating factors); range for all metabolites

Reference 2

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-06-02 to 2007-07-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study (OECD test guideline 305C)

Qualifier:

according to guideline

Guideline:

OECD Guideline 305 C (Bioaccumulation: Test for the Degree of Bioconcentration in Fish)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
Not applicable

Radiolabelling:

yes

Details on sampling:

Two pools, each of 3 fish, were sampled on the first and last days of the exposure phase and the final day of the depuration phase for measurement of lipid content.

Preparation of fish samples for measurement of radioactivity: Samples of edible (fillet) and non-edible fish portions were homogenised by mincing with scissors and levels of radioactivity determined by combustion/LSC.

Vehicle:

yes

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

PREPARATION AND APPLICATION OF TEST SOLUTION
- Method:
The fish were exposed to radiolabelled test item as a solution in water at a nominal concentration of 0.05 µg/L. [14C]-test item was used without radiodilution. A dose solution of [14C]-test item in dimethylformamide (DMF) was prepared to provide sufficient dose solution for at least ten days. Dose solutions were stored at ca +4°C until required.

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Details on test organisms:

TEST ORGANISM
- Common name: Rainbow Trout
- Source: Donnington Trout Farm (UK)
- Length at study initiation: 4 - 6 cm
- Age at study initiation: <1 year
- Weight at study initiation: 1 - 2 g
- Acclimatisation: in holding tanks for a period of at least 2 weeks

150 fish were added to each of the test and control tanks (20 fish in the effluent tank) resulting in a maximum loading of 1 fish per 10 litres per day. After 29 days of exposure to the test substance the fish were transferred to equivalent tanks without test substance for a depuration period of 42 days.

Route of exposure:

aqueous

Test type:

flow-through

Water / sediment media type:

natural water: freshwater

Total exposure / uptake duration:

29 d

Total depuration duration:

42 d

Hardness:

155 - 204 mg/l

Test temperature:

13.8 - 15.2 °C.

pH:

7.2 - 8.03

Dissolved oxygen:

6.85 - 8.89 mg O2/L

Details on test conditions:

TEST SYSTEM
- Test vessel: Glass aquarium (120 L)
- Type: open
- Type of flow-through: continuous flow through (1440 litres per day (nominal flow rate 1 litre/minute)
- Photoperiod: 16 hours light and 8 hours darkness

TEST MEDIUM / WATER PARAMETERS
- Temperature, pH and oxygen content of the water were generally measured daily throughout the study
- Total organic carbon was measured 24 and 48 hours prior to initiation of the exposure period, before addition of the fish and at least once a week during both exposure and depuration periods.

Nominal and measured concentrations:

nominal concentrations: 0.05 µg/L test substance

Reference substance (positive control):

no

Type:

BCF

Value:

66 - 179 dimensionless

Basis:

other: for fish portions and whole-fish

Time of plateau:

14 d

Calculation basis:

steady state

Details on kinetic parameters:

Kinetic parameters were determined using a WinNolin software package. BCF values (kinetic) were calculated as 191 (whole-fish), 95 (edible) and 258 (nonedible).
The corresponding uptake rate constants were 89 (whole-fish), 29 (edible) and 153 (non-edible). Elimination of radioactive residues during the depuration phase was relatively slow with DT50 values of 6 - 8 days for all tissues. The time taken for elimination of 90% radioactive residues (DT90) was 36 - 44 days for all tissues.

Metabolites:

Not applicable.

Details on results:

-Total radioactive residues in fish:
Uptake of radioactivity in fish was relatively gradual and reached steady-state concentrations between Days 14 and 29. Mean concentrations of radioactivity were highest in the non-edible fish portions and were in the range 0.0086 - 0.0098 (µg/g at steadystate. Mean concentrations of radioactivity in the edible portion were 0.0029 - 0.0040 µg/g and 0.0066 - 0.0075 µg/g in the whole-fish at steady-state. The corresponding steady-state bioconcentration factors were low. Mean bioconcentration factors at steady-state were 66 (edible), 179 (non-edible) and 135 (whole-fish).

- Lipid analysis:
Bioconcentration factors relative to lipid content (assuming accumulation occurs only in the lipid) were determined due to the high log Pow value of 8.9 (calculated). BCF(lipid) values were in the range 2222 - 2637.

- Chromatographic analysis of fish extracts:
Test item accounted for 42 - 48% sample radioactivity in edible fish portions and 24 - 27% sample radioactivity non-edible fish portions. Bioconcentration factors for test item were low with a mean of 31 for edible portions of fish and 50 for non-edible portions offish

Low levels of accumulation of the test item were observed during the 29 day exposure period. Between days 14 and 29 of the exposure phase, concentrations in fish portions were within ± 20% of the mean concentration indicating that steady-state was achieved during the exposure period. Model predictions from the kinetic analysis indicated that the time taken to achieve 90% of steady-state concentrations was 35 - 40 days continuous exposure. Bioconcentration factors were low for both fish portions and whole-fish. Mean bioconcentration factors at steady-state were in the range 66 - 179. Accumulation of radioactive residues was in the order edible < whole-fish < non-edible tissues and well below 1000, therefore the test item is not considered to be bioaccumulative. Elimination of the test item during the depuration phase was relatively slow. Kinetic analysis indicated that approximately 90% of the radioactive residues were eliminated in 36 - 44 days.

Reference 3

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1987-03-19 to 1987-06-08

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Similar to OECD Guideline 305 C, No GLP statement

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 305 C (Bioaccumulation: Test for the Degree of Bioconcentration in Fish)

Deviations:

no

GLP compliance:

no

Radiolabelling:

no

Vehicle:

no

Test organisms (species):

Cyprinus carpio

Details on test organisms:

Average body weight at study initiation: 27.6 g
Average body length at study initiation: 10.2 cm

Route of exposure:

aqueous

Test type:

not specified

Water / sediment media type:

not specified

Total exposure / uptake duration:

4 wk

Total depuration duration:

28 d

Hardness:

No data

Test temperature:

No data

pH:

No data

Dissolved oxygen:

No data

Details on test conditions:

No data

Nominal and measured concentrations:

Nominal: 0.1 and 1 mg/L

Type:

BCF

Value:

22.5 dimensionless

Remarks on result:

other: Mean of 2 replication

Remarks:

Conc.in environment / dose:1 mg/L

Type:

BCF

Value:

20 dimensionless

Remarks on result:

other: Mean of 2 replication

Remarks:

Conc.in environment / dose:0.1 mg/L

Details on results:

The bioconcentration factors of the test substance are 20 - 22.5 and the compound is not accumulative in fish. Appearance of test fish was normal by aquarium-side observations.
The recovery ratio was:
- fish: 89.0 %
- Water (1 mg test item/L): 93.3 %
- Water (0.1 test item/L): 95.8 %

The Limit of determination was:
- fish: 0.23 - 0.35 µg/g
- Water (1 mg test item/L): 0.032 - 0.05 µg/mL
- Water (0.1 test item/L): 0.0031 - 0.0049 µg/mL

Reference 4

Endpoint:

bioaccumulation in aquatic species: fish

Remarks:

The BCF values for the predicted metabolites (see chapter 5.2.1 for details) >=0.1% and with a logKow >4 were modeled.

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
OASIS Catalogic v5.14.1.5

2. MODEL (incl. version number)
BCF base-line model v04.11 - November, 2019

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See section 'Test Material'.

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).
- The model estimates the Bioconcentration factor (BCF) as required information point according to Regulation (EC) No 1907/2006 [REACH], Annex IX, 9.3.2 Bioaccumulation in aquatic species (preferably fish);
further related predictions: Apparent effect of mitigating factors / Maximum bioconcentration factor (BCFmax) / Maximum diameter of energetically stable conformers / Whole body primary biotransformation half-life / Metabolic biotransformation rate constant Km / Metabolites and their quantitative distribution
- See attached QPRF for reliability assessment.

Principles of method if other than guideline:

Calculation using Catalogic v.5.14.1.5, BCF base-line model v.04.11

GLP compliance:

no

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: OASIS Catalogic v5.14.1.5 [BCF base line model - v.04.11]

Key result

Type:

BCF

Value:

>= 4.36 - <= 363 L/kg

Remarks on result:

other: BCF corrected (considering all mitigating factors); range for all metabolites

Description of key information

Neither the parent compound nor the identified metabolites significantly accumulate in organisms.

Additional information

The bioaccumulative potential of the substance has been assessed in two experimental studies according or similar to OECD TG 305. The key study with a validity score of 1 was conducted according to OECD TG 305 under consideration of GLP. Radioactively labeled test material was used. Rainbow trout were exposed to 0.05 µg/L test substance in a continuous flow-through system. Low levels of accumulation of the test item were observed during the 29 day exposure period. Between days 14 and 29 of the exposure phase, concentrations in fish portions were within ± 20% of the mean concentration indicating that steady-state was achieved during the exposure period. Mean bioconcentration factors at steady-state were in the range 66 - 179. Accumulation of radioactive residues was in the order edible < whole-fish < non-edible tissues and well below 1000, therefore the test item is not considered to be bioaccumulative. Elimination of the test item during the depuration phase was relatively slow. Kinetic analysis indicated that approximately 90% of the radioactive residues were eliminated in 36 - 44 days.

A second study was conducted similar to OECD TG 305. Cyprinus carpio was exposed to nominal concentrations of 0.1 and 1 mg/L test substance. The resulting BCF values were 20 and 22.5 L/kg respectively.

In addition to the parent compound, 126 metabolites identified in chapter 5.2.1 and four in 5.2.2 were additionally assessed with the Catalogic BCF baseline model v.04.11 included in the Catalogic platform v5.14.1.5. The applicability domain of the model consists of three layers: (1) the parameter domain, (2) the structural fragment domain, and (3) the mechanistic domain. The compounds were within the parameter ranges of the parameter domain, i.e. the logKow, the molecular weight and the water solubility were within the range of the domain. The compounds were also within the mechanistic domain. Thus, they are taken up by passive diffusion only. Regarding the structure domain, the model identified 47 to 85% correct fragments and 15 to 53% unknown fragments for the metabolites from chapter 5.2.1, respectively 53 to 67 % correct fragments and 33 to 47 % unknown fragments for the metabolites from chapter 5.2.2. Due to the result of the structure domain, the compounds must be classified as out of domain. Nevertheless, the BCF results are regarded as valid and suitable. The model calculates the BCF by applying mitigating factors to the baseline BCF taking into account important mitigating parameters like metabolism, size, acids, phenols and water solubility. The compounds have BCF values ranging from 2.69 to 363 L/kg. Additionally, the model also calculates the molecular size (Diammax average). The compounds have values from 1.48 to 2.69 nm. A threshold of 1.7 nm is generally regarded as indicator of a limited bioaccumulative potential due to hindered uptake through biological membranes (cf. ECHA’s Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.11: PBT/vPvB assessment).

In conclusion, neither the parent substance nor the identified metabolites are expected to significantly bioaccumulate.