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Bioaccumulation: aquatic / sediment

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Endpoint:
bioaccumulation in aquatic species, other
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
weight of evidence
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
Remarks:
Well documented QSAR model for prediction of BCF; according to the model's application domain index, the read-across has a good reliability.
Principles of method if other than guideline:
The BCF is estimated based on several molecular descriptors. The applicability domain of predictions is assessed using an Applicability Domain Index (ADI) calculated by grouping several other indices, e.g. by a similarity index that consider molecule's fingerprint and structural aspects (count of atoms, rings and relevant fragments).
GLP compliance:
no
Test organisms (species):
other: fish
Details on estimation of bioconcentration:
BASIS INFORMATION
- Measured/calculated logPow: calculated

BASIS FOR CALCULATION OF BCF
- Estimation software: VEGA CAESAR v2.1.13 implemented in the VEGA tool v.1.0.8
- Result based on calculated log Pow of: 4.18 (calculated by VEGA)
Type:
BCF
Value:
465 L/kg
Basis:
whole body w.w.
Calculation basis:
steady state
Remarks on result:
other: The substance is within the model's applicability domain (good reliability).

Compound SMILES: Oc1c(cc(cc1C(C)(C)C)C)C(C)(C)C
Experimental BCF value: 3.2 [log(L/kg)]
BCF p
rediction: 3.1 [log(L/kg)]
BCF p
rediction: 1265 [L/kg]
ALogP: 4.85 [log units]
MLogP: 4.18 [log units]
Reliability: Compound is in model Applicability Domain
Remarks for the prediction: none

Similar substances with predicted and experimental values

CAS no.

SMILES

Similarity

coefficient

BCF [log(L/kg)]

experimental

predicted

128-37-0

Oc1c(cc(cc1C(C)(C)C)C)C(C)(C)C

1

3.2

3.42

4130-42-1

Oc1c(cc(cc1C(C)(C)C)CC)C(C)(C)C

0.985

3.59

3.3

96-76-4

Oc1ccc(cc1C(C)(C)C)C(C)(C)C

0.978

2.51

3.65

732-26-3

Oc1c(cc(cc1C(C)(C)C)C(C)(C)C)C(C)(C)C

0.962

4.18

3.11

5510-99-6

Oc1c(cccc1C(C)CC)C(C)CC

0.922

2.55

3.1

98-54-4

Oc1ccc(cc1)C(C)(C)C

0.881

1.75

1.16

Assessment of the applicability domain

Global AD Index

AD Index = 0.988

Explanation: read-across seems to be reliable.

 

Highest similarity found for similar compounds

Highest similarity = 1

Explanation: the highest similarity value found for similar compounds is adequate for a reliable read-across.

 

Lowest similarity found for similar compounds

Lowest similarity = 0.978

Explanation: the lowest similarity value found for similar compounds is adequate for a reliable read-across.

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
15 May to 22 August 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Data from reliable source. Only basic information are available in Japanese. The full test report is not available at present. The data from this source are known to be well documented and the test are performed according to GLP and OECD guidelines; however, the wide range of BCF values cannot be explained based on the available information.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 305 C (Bioaccumulation: Test for the Degree of Bioconcentration in Fish)
Principles of method if other than guideline:
Method: "Bioaccumulation test of chemical substance in fish and shellfish" stipulated in the Japanese Order Prescribing the Items of the Test Relating to the New Chemical Substance (1974)
GLP compliance:
not specified
Vehicle:
yes
Details on preparation of test solutions, spiked fish food or sediment:
PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: dispersion method (stock solution fo 500 mg/L; 0.5 g BHT and 10 g HCO-40, dissolved in acetone (25 mL) + water (5 mL); acteone removed in rotary evaporator; addition of hot water, let cool to room temperature)
- Controls:
- Chemical name of vehicle (organic solvent, emulsifier or dispersant): HCO-40 (hydrogenated castor oil)
- Concentration of vehicle in test medium (stock solution and final test solution(s) at different concentrations and in control(s)): final test solution: 500 µg/L BHT = 10 mg/L HCO-40; 50 µg/L BHT = 1 mg/L HCO-40; 5 µg/L BHT = 0.1 mg/L HCO-40
- Evidence of undissolved material (e.g. precipitate, surface film, etc): no
Test organisms (species):
Cyprinus carpio
Details on test organisms:
TEST ORGANISM
- Common name: Common carp
- Strain:
- Source:
- Age at study initiation (mean and range, SD):
- Length at study initiation (lenght definition, mean, range and SD): 10.6 cm
- Weight at study initiation (mean and range, SD): 29.2 g
- Weight at termination (mean and range, SD):
- Method of breeding:
- Health status: disinfected for 24 h in chlortetracycline solution
- Description of housing/holding area:
- Feeding during test
- Food type:
- Amount:
- Frequency:

ACCLIMATION
- Acclimation period: 14 days
- Acclimation conditions (same as test or not):
- Type and amount of food:
- Feeding frequency:
- Health during acclimation (any mortality observed):
Route of exposure:
aqueous
Test type:
flow-through
Water / sediment media type:
natural water: freshwater
Total exposure / uptake duration:
8 wk
Test temperature:
25 °C
Details on test conditions:
The test is performed under flow through conditions and test water is analysed twice a week.
TEST SYSTEM
- Test vessel:
- Type (delete if not applicable): open
- Material, size, headspace, fill volume: glass tank, 100 L
- Type of flow-through (e.g. peristaltic or proportional diluter): no data
- Renewal rate of test solution (frequency/flow rate): 1152 L/d (stock solution: dilution water = 2 mL/min to 800 mL/min)


RANGE-FINDING / PRELIMINARY STUDY
- Results used to determine the conditions for the definitive study: 48-h LC50 (Oryzias latipes) = 5 mg/L
Nominal and measured concentrations:
0.005 mg/l
Type:
BCF
Value:
839 L/kg
Basis:
whole body w.w.
Remarks on result:
other: 8 weeks of exposure; range of BCF values over whole exposure period: 330 to 1800 L/kg
Remarks:
Conc.in environment / dose:5 µg/L (nominal)
Type:
BCF
Value:
1 277 L/kg
Basis:
whole body w.w.
Remarks on result:
other: 8 weeks of exposure; range of BCF values over whole exposure period: 230 to 2500 L/kg
Remarks:
Conc.in environment / dose:50 µg/L (nominal)
Type:
BCF
Value:
952 L/kg
Basis:
whole body w.w.
Remarks on result:
other: 6 weeks of exposure; range of BCF values: 220 to 2800 L/kg; exposure stopped as fish showed curved backbones
Remarks:
Conc.in environment / dose:500 µg/L (nominal)
Details on results:
- Mortality of test organisms: 0%
- Behavioural abnormalities: no
- Other biological observations: Fish abnormalities occurred only in the first concentration group. Weakness after the start of the test, symptoms of indigestion is observed, malformations of the spine were observed in the second week. This anomaly was observed in 14 stomach 4 fish, 2 fish of the spine curvature among was remarkable. This condition it is believed to be due to toxicity.
- Mortality and/or behavioural abnormalities of control: -
- Loss of test substance during test period:
- Results with vehicle control:

Analytical verification of test concentrations

Concentration

(µg/L; nominal)

Dispersant

(HCO-40)

concentration

(µg/L)

Mean measured concentrations (µg/L)

2 w

4 w

6 w

8 w

500

10000

478

467

457

-

50

1000

45.2

39.7

39.0

39.0

5

100

4.11

3.63

3.70

3.82

 

 

Bioconcentration factors (L/kg)

Concentration

(µg/L; nominal)

2 weeks

4 weeks

6 weeks

8 weeks

500

980

1400

570

2800

2500

660

220

2500

1700

1400

740

1400

410

710

1500

-

50

380

780

710

290

1000

840

380

300

860

230

1100

2500

5

520

780

1100

1800

620

330

440

700

420

1100

760

1500

 

Validity criteria fulfilled:
yes
Conclusions:
The mean bioconcentration factors of the study are 781 L/kg (50 µg/L) and 839 L/kg (5 µg/kg). Therefore, the substance is assessed to have a bioaccumulatin potential, howeverm, the substance is not B/vB.
Executive summary:

An experiment with Cyprinus carpio was conducted by MITI in 1992 to measure bioconcentration factor (BCF) of 2,6 -di-tert-butyl-p-cresol (BHT) in the aquatic environment. This test was performed in accordance with "Bioaccumulation test of chemical substance in fish and shellfish" stipulated in the Japanese Order Prescribing the Items of the Test relating to the new chemical substance (1974). This guideline corresponds to OECD guideline 305C. The test water was analysed twice a week, the total exposure time was 56 days. As result a bioconcentration factor (BCF) in the range between 330 to 1800 is reported at a nominal concentration level of 0.005 mg/L.

The exposure in the highest test concentration (500 µg/K) was stopped after 6 weeks of exposure as signs of toxicity occurred; therefore, the BCF data from this concentration level should not be used to assess the bioaccumulation potential.

The bioconcentration factors in the 50 µg/L level range from 230 to 2500 L/kg, with an average of 781 over the whole exposure period.

The bioconcentration factors in the 5µg/L level range from 330 to 1800 L/g, with an average BCF of 839 L/kg. The BCF values were calculated over the whole exposure period as no trend could be observed.

It can be concluded that the substance has a potential to bioaccumulate; however, it does not meet the crtieria for being B/vB.

Endpoint:
bioaccumulation in aquatic species, other
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
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
Remarks:
Scientifically accepted calculation method; substance within applicability
Principles of method if other than guideline:
Calculation with EPI Suite v4.11: BCFBAF v3.01, Estimation of BCF, BAF and biotransformation rate using
GLP compliance:
no
Test organisms (species):
other: fish
Details on estimation of bioconcentration:
BASIS INFORMATION
- Measured/calculated logPow: measured

BASIS FOR CALCULATION OF BCF
- Estimation software: EPI Suite v4.11 - BCFBAF v3.01 (US EPA, 2012)
- Result based on measured log Pow of: 5.10 (see IUCLID Ch. 4.7; Shell, 1983)
Type:
BCF
Value:
646 L/kg
Basis:
whole body w.w.
Calculation basis:
steady state
Remarks on result:
other: log BCF = 2.81; model: Meylan et al. (1997/1999). The substance is within the applicability domain.

QPRF: EPI Suite v4.11 - BCFBAF v3.01

1.

Substance

2,6-di-tert-butyl-p-cresol

2.

General information

 

2.1

Date of QPRF

12 May 2015

2.2

QPRF author and contact details

LANXESS Deutschland GmbH

3.

Prediction

3.1

Endpoint
(OECD Principle 1)

Endpoint

Bioaccumulation (aquatic)

Dependent variable

- Bioconcentration factor (BCF)

3.2

Algorithm
(OECD Principle 2)

Model or submodel name

BCFBAF: Submodel: Bioconcentration factor (BCF; Meylan et al., 1997/1999)

Model version

v. 3.01

Reference to QMRF

Estimation of Bioconcentration in fish using BCFBAF v3.01 (EPI Suite v4.11)

Predicted value (model result)

See “Results and discussion”

Input for prediction

Chemical structure via CAS number or SMILES; log Kow (optional)

Descriptor values

- SMILES: structure of the compound as SMILES notation

- log Kow

- Molecular weight

3.3

Applicability domain
(OECD principle 3)

Domains:

 

a) Ionic/non-Ionic

The substance is non-ionic under environmentally relevant conditions (weak acid, pKa = 12.26, calculated).

 

b) Molecular weight (range of test data set):

- Ionic: 68.08 to 991.80

- Non-ionic: 68.08 to 959.17

(On-Line BCFBAF Help File, Ch. 7.1.3 Estimation Domain and Appendix G)

The substance is within the range (220.36 g/mol).

 

c) log Kow (range of test data set):

- Ionic: -6.50 to 11.26

- Non-ionic: -1.37 to 11.26

(On-Line BCFBAF Help File, Ch. 7.1.3 Estimation Domain and Appendix G)

The substance is within the range (log Kow = 5.10, measured).

 

 

d) Maximum number of instances of correction factor in any of the training set compounds (On-Line BCFBAF Help File, Appendix E)

The number of instances of the correction factor is within the limits of the training set.

3.4

The uncertainty of the prediction
(OECD principle 4)

Statistical accuracy of the training data set (non-ionic plus ionic data):

- Correlation coefficient (r2) = 0.833

- Standard deviation = 0.502 log units

- Absolute mean error = 0.382 log units

3.5

The chemical mechanisms according to the model underpinning the predicted result
(OECD principle 5)

The BCF model is mainly based on the relationship between bioconcentration and hydrophobicity. The model also takes into account the chemical structure and the ionic/non-ionic character of the substance.

4.

References

- Meylan, W.M., Howard, P.H, Aronson, D., Printup, H. and S. Gouchie. 1997. "Improved Method for Estimating Bioconcentration Factor (BCF) from Octanol-Water Partition Coefficient", SRC TR-97-006 (2nd Update), July 22, 1997; prepared for: Robert S. Boethling, EPA-OPPT, Washington, DC; Contract No. 68-D5-0012; prepared by: ; Syracuse Research Corp., Environmental Science Center, 6225 Running Ridge Road, North Syracuse, NY 13212.

- Meylan, WM, Howard, PH, Boethling, RS et al. 1999. Improved Method for Estimating Bioconcentration / Bioaccumulation Factor from Octanol/Water Partition Coefficient. Environ. Toxicol. Chem. 18(4): 664-672 (1999). 

- US EPA (2012). On-Line BCFBAF Help File.

 

Validity criteria fulfilled:
yes
Remarks:
substance within applicability domain
Conclusions:
Based on a log Kow of 5.10, the BCF was estimated to be 646 L/kg ww.
Executive summary:

The BCF was estimated using the BCFBAF v3.01 of EPI Suite v4.11 (US EPA, 2012). The model calculates the BCF based on the log Kow (Meylan et al., 1997/1999). A measured log Kow was provided (log Kow = 5.10; see IUCLID Ch. 4.7). Compared to the parameter provided in the User's Guide of EPI Suite, the substance is within the applicability domain of the model. The BCF was estimated to be 646 L/kg ww.

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented QSAR model for prediction of BCF; according to the model's application domain index, the read-across has a good reliability.
Principles of method if other than guideline:
The model performs a read-across to substances with similar structures and provides a quantitative prediction of the bioconcentration factor (BCF) in fish, given in log(L/kg). The read-across is based on the similarity index developed inside the VEGA platform; the index takes into account several structural aspects of the compounds, such as their fingerprint, the number of atoms, of cycles, of heteroatoms, of halogen atoms, and of particular fragments (such as nitro groups). On the basis of this structural similarity index, the three compounds from the dataset resulting most similar to the chemical to be predicted are taken into account: the estimated BCF value is calculated as the weighted average value of the experimental values of the three selected compounds, using their similarity values as weight.
GLP compliance:
no
Test organisms (species):
other: fish
Type:
BCF
Value:
1 265 L/kg
Basis:
whole body w.w.
Calculation basis:
steady state
Remarks on result:
other: The substance is within the model's applicability domain (good reliability).

Compound SMILES: Oc1c(cc(cc1C(C)(C)C)C)C(C)(C)C
Experimental BCF value: 3.2 [log(L/kg)]
BCF p
rediction: 3.1 [log(L/kg)]
BCF p
rediction: 1265 [L/kg]
ALogP: 4.85 [log units]
MLogP: 4.18 [log units]
Reliability: Compound is in model Applicability Domain
Remarks for the prediction: none

Similar substances with predicted and experimental values

CAS no.

SMILES

Similarity

coefficient

BCF [log(L/kg)]

experimental

predicted

128-37-0

Oc1c(cc(cc1C(C)(C)C)C)C(C)(C)C

1

3.2

3.42

4130-42-1

Oc1c(cc(cc1C(C)(C)C)CC)C(C)(C)C

0.985

3.59

3.3

96-76-4

Oc1ccc(cc1C(C)(C)C)C(C)(C)C

0.978

2.51

3.65

732-26-3

Oc1c(cc(cc1C(C)(C)C)C(C)(C)C)C(C)(C)C

0.962

4.18

3.11

5510-99-6

Oc1c(cccc1C(C)CC)C(C)CC

0.922

2.55

3.1

98-54-4

Oc1ccc(cc1)C(C)(C)C

0.881

1.75

1.16

Assessment of the applicability domain

Global AD Index

AD Index = 0.988

Explanation: read-across seems to be reliable.

 

Highest similarity found for similar compounds

Highest similarity = 1

Explanation: the highest similarity value found for similar compounds is adequate for a reliable read-across.

 

Lowest similarity found for similar compounds

Lowest similarity = 0.978

Explanation: the lowest similarity value found for similar compounds is adequate for a reliable read-across.

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Significant methodological deficiencies: number of exposed organisms too small (i.e. fish = 2), chemical analysis
Principles of method if other than guideline:
In this paper, the behaviors of BHT were studied in a model ecosystem containing soil, water and fish or of snails, daphnids, and algae by using
radioactive 14C-BHT labelled with C at the phenyl carbons.
GLP compliance:
no
Radiolabelling:
yes
Vehicle:
no
Details on preparation of test solutions, spiked fish food or sediment:
Soil characteristics: sand 80%, silt 12%, clay 8%, organic matter 1.8%, pH 5.8
Test organisms (species):
Cyprinus carpio
Details on test organisms:
Fish:
Cyprinus carpio, approximately 15-25 g, were purchased from the Nango Fisheries Center, Shiga Pref. and acclimatized in dechlorinated tap water for two weeks at 25°C prior to use.
Snails:
Cypangopaludina japonica, 15-25 g, from Katada Fisheries Union, Shiga Pref. were acclimatized on Katano soil flooded with dechlorinated water.
Daphnids:
Daphnia pulex, from Nihon Dobutsu Co. were acclimatized in flooded water on Katano soil.
Algae:
Fillamentous green algae and chlorella, appearing and grown in the culture solution for the growth of chlorella, were used.
Route of exposure:
aqueous
Test type:
static
Water / sediment media type:
natural water: freshwater
Total exposure / uptake duration:
28 d
Test temperature:
25 +/- 2°C
Dissolved oxygen:
constant air supply
Details on test conditions:
Two fish used in each test, weight of fish: 15-25 g - fish fed in experiment A and B, no feeding in experiment C
Reference substance (positive control):
no
Type:
BCF
Value:
>= 13 - <= 17
Basis:
whole body w.w.
Calculation basis:
steady state
Remarks on result:
other: results after test duration of 28 days
Metabolites:
Observed degradation products of BHT: BHT-OOH, BHT-OH, BHT-CH2OH, BHT-CHO, and BHT-COOH.
Details on results:
A.) Only 1-2% of the applied radioactivity was translocated in fish. The BCF decreased with time. The same holds true for the degradation products of BHT: BHT-OOH, BHT-OH, BHT-CH2OH, BHT-CHO, and BHT-COOH. For the degradation products a maximum BCF of 26 was determined after 7 days of exposure (BHT-OH). From the results the authors concluded that the compounds in fish were excreted or metabolized fairly rapidly.

B.) During this experiment ca. 50% of applied radioactivity evaporated into the atmosphere. The BCF values of the degradation products BHT-OH, BHT-CHO, and BHT-OOH/BHT-COOH (for the last two compounds there are discrepancies between the BCF value cited in the table and the text) at the 7th day were very high: 347, 151, and 101, respectively. The authors concluded that at the beginning fish incorporated BHT, then metabolized it before excretion (in the water phase BHT concentration decreased to a minimum value within 3 days due to sorption of BHT to the soil).

C.) During this experiment 15-18% of applied radioactivity evaporated into the atmosphere.

Table 1: Bioaccumulation Ratios (BR's) of BHT and its decomposed products in carps (experiment A )

Exposure (days) 7 14 28
BHT 25 22 17
BHT-OOH 4 2 1
BHT-OH 26 11 6
BHT-CH2OH 20 15 8
BHT-CHO 13 18 6
BHT-COOH 2 4 6
Others* 52 44 22
Origin** 83 37 13
Total14C 29 18 9

* containing 4 major spots (silicagel-solvent system A)

** containing more than 15 spots (silicagel-solvent system B)

Table 2: Bioaccumulation Ratios (BR's) of BHT and its decomposed products in carps (experiment B )

Exposure (days) 7 14 28
BHT 16 21 13
BHT-OOH 101 114 34
BHT-OH 347 75 29
BHT-CH2OH 54 12 7
BHT-CHO 151 75 45
BHT-COOH 30 8 6
Others* 83 24 12
Origin** 95 30 18
Total14C 49 30 16

* containing 4 major spots (silicagel-solvent system A)

** containing more than 15 spots (silicagel-solvent system B)

Table 3: Distribution of 14C in experiment C

% of applied14C
Exposure(days) 7 14 28
Water 8.8 11.7 15.9
Soil 73.7 72.5 65.7
Organisms 0.3 0.5 0.4
Total 82.8 84.7 82 .0

Table 3: The changes of BR's of 14C-phenyl-BHT and its metabolites in four organisms.

Organism Fish Snails Daphnids Algae
Exposure time (day) 7 14 28 7 14 28 7 14 28 7 14 28
Extracted14C  
BHT 15 13 2 91 125 30 73 65 --- * 88 98 38
BHT-OOH 11 13 3 --- 34 5 --- --- --- 33 82 10
BHT-OH 9 8 1 5 34 1 --- --- --- 29 25 3
BHT-CH2OH 14 12 5 5 32 6 --- --- --- 23 76 8
BHT-CHO 21 21 3 --- 38 4 --- --- --- 35 67 16
BHT-COOH 3 4 4 4 9 5 12 --- --- 9 6 2
Unknown-1 13 --- --- --- --- --- --- --- --- 55 62 19
Unknown-2 11 30 --- --- --- --- --- --- --- 61 51 19
Unknown-3 14 23 --- --- --- --- --- --- ---
Others 21 20 29 8 46 2o 64 59 28 5 3 4
Origin** 151 121 86 15 46 16 56 37 34 6 14 18
Total14C 35 34 17 12 39 23 40 52 30 29 75 20

* Not detected

** containing more than 15 spots (silicagel-solvent system B)

Validity criteria fulfilled:
yes
Conclusions:
THe behaviors of BHT were studied in a model ecosystem containing soil, water and fish or of snails, daphnids, and algae by using
radioactive 14C-BHT labelled with C at the phenyl carbons. After 28 days a BCF inbetween 13 and 17 was found (Inui, H., Akutsu, S., Itoh, K., Matsuo, M. & Miyamoto, J., 1979).
Executive summary:

Inui et al. (1979) studied the behaviour of BHT was studied in a model ecosystem containing of soil, water and fish or of snails, daphnids, and algae by applying radioactive 14C-BHT (labelled with C at the phenyl carbons).

The bioconcentration factor (BCF) was determined in a model ecosystem under three different test conditions. After 28 days BCF values between 13 and 17 was found. However, the BCF values were derived from model ecosystems where adsorbant materials (soil) was present. There were only 2 fish in each experimental condition. It is not clear whether this test was performed in a flow through system, and finally, degradation of the substance is not taken into account.

Endpoint:
bioaccumulation in aquatic species, other
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Methods were validated by US EPA using statistical external validation; based on the mean absolute errors of the models the confidence in the predicted results is low.
Principles of method if other than guideline:
T.E.S.T. is a toxicity estimation software tool. The program requires only the molecular structure of the test item, all other molecular descriptors which are required to estimate the toxicity are calculated within the tool itself. The molecular descriptors describe physical characteristics of the molecule (e.g. E-state values and E-state counts, constitutional descriptors, topological descriptors, walk and path counts, connectivity, information content, 2d autocorrelation, Burden eigenvalue, molecular property (such as the octanol-water partition coefficient), Kappa, hydrogen bond acceptor/donor counts, molecular distance edge, and molecular fragment counts). Each of the available methods uses a different set of these descriptors to estimate the toxicity.
The bioaccumulation factor (BCF) was estimated using the following methods: hierarchical clustering; FDA; single model; group contribution; nearest neighbor; consensus. The methods were validated using statistical external validation using separate training and test data sets.
The experimental data set was obtained from several different databases (Dimitrov et al., 2005; Arnot and Gobas, 2006; EURAS; Zhao, 2008). After removing data on salts, mixtures and ambiguous compounds, the final data set contained 676 chemicals.

References:
- Dimitrov, S., N. Dimitrova, T. Parkerton, M. Combers, M. Bonnell, and O. Mekenyan. 2005. Base-line model for identifying the bioaccumulation potential of chemicals. SAR and QSAR in Environmental Research 16:531-554.
- Arnot, J.A., and F.A.P.C. Gobas. 2006. A review of bioconcentration factor (BCF) and bioaccumulation factor (BAF) assessments for organic chemicals in aquatic organisms. Environ. Rev. 14:257-297.
- EURAS. Establishing a bioconcentration factor (BCF) Gold Standard Database. EURAS [cited 5/20/09]. Available from http://www.euras.be/eng/project.asp?ProjectId=92.
- Zhao, C.; Boriani, E.; Chana, A.; Roncaglioni, A.; Benfenati, E. 2008. A new hybrid system of QSAR models for predicting bioconcentration factors (BCF). Chemosphere 73:1701-1707.
GLP compliance:
no
Test organisms (species):
other: fish
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: US EPA T.E.S.T. v4.1

Applied estimation methods:
- Hierarchical clustering
- FDA
- Single model
- Group contribution
- Nearest neighbor
- Consensus
Type:
BCF
Value:
1 656 L/kg
Basis:
whole body w.w.
Calculation basis:
steady state
Remarks on result:
other: Method: consensus (average of reasonable results from all models); log BCF = 3.22; based on the mean absolute error, the confidence in the predicted BCF values is low.
Type:
BCF
Value:
1 581 L/kg
Basis:
whole body w.w.
Calculation basis:
steady state
Remarks on result:
other: experimental value from data set (log BCF = 3.20)

Overview on the results of the six methods of US EPA T.E.S.T. v4.1 (MAE = mean absolute error; SC = similarity coefficient)

Method

Predicted value

MAE (in log10)

External test set

Training set

log BCF

BCF

Entire set

SC >= 0.5

Entire set

SC >= 0.5

Consensus method

3.22

1,655.92

0.51

0.57

0.42

0.77

Hierarchical clustering

3.13

1,345.80

(863.43-2097.64)

0.54

0.66

0.23

0.29

Single model

2.73

531.01 (39.75-7093.57)

0.54

0.69

0.53

0.79

Group contribution

3.02

1,036.05

(45.37-23661.25)

0.62

0.27

0.60

0.70

FDA

3.67

4,675.96

(396.02-55210.38)

0.57

0.42

0.53

1.09

Nearest neighbor

3.56

3,696.39

0.60

1.46

0.55

1.32

Validity criteria fulfilled:
not applicable
Conclusions:
The BCF was estimated using the Consensus method of T.E.S.T. v4.1 8US EPA, 2012) to be 1656 L/kg. The substance is within the applicability domain of the models; however, based on the mean absolute errors of the models the confidence in the predicted results is low.
Executive summary:

The BCF was estimated using the QSAR models of T.E.S.T. v4.1 (US EPA, 2012). The model uses five estimation methods to predict the BCF. In addition the Consensus methods calculates the final BCF based on the results of the individual models. The substance was within the applicability domain of all models. The models also calculate the mean absolute error (MAE) of the results as a measure to judge the confidence in the results. As the MAE of similar substances is higher than that of the entire training set and/or external test set, the confidence in the estimated BCF values is low.

According to the Consensus method, the BCF was calculated to be 1656 L/kg. The value is supported by an experimental BCF from the model's experimental database (BCF = 1581 L/kg).

Description of key information

The test substance has a moderate potential to accumulate in aquatic organisms, however BHT is not regarded as B according to REACH Annex XIII, as the BCF is below 2000.

Key value for chemical safety assessment

BCF (aquatic species):
1 277 dimensionless

Additional information

A bioconcentration study with Cyprinus carpio was conducted by MITI in 1992 to measure a bioconcentration factor (BCF) of 2,6 -di-tert-butyl-p-cresol (BHT) in the aquatic environment. This test was performed in accordance with the national Japanese guidance "Bioaccumulation test of chemical substance in fish and shellfish" stipulated in the Japanese Order Prescribing the Items of the Test relating to the new chemical substance (1974). This guideline corresponds to OECD guideline 305C. The test water was analysed twice a week, the total exposure time was 56 days. Three concentration levels were tested (5, 50 and 500 µg/L, nominal). In the highest test concentration, the exposure was terminated after 6 weeks of exposure as the fish showed curved backbones due to toxic effects of the compound in this high concentration. At both remaining levels, the bioconcentration factors showed a wide range (50 µg/L: 230 to 2500, mean = 839; 5 µg/L: 330 to 1800, mean = 1277).

The data are from a reliable source; however, only basic information are available in Japanese. The full test report is not available at present. The data from this source are known to be well documented and the test are performed according to GLP and OECD guidelines; however, the wide range of BCF values cannot be explained based on the available information. Therefore, this study is only reliable with restrictions.

Another experimental study is available from Inui et al. (1979) who studied the behaviour of BHT in a model ecosystem containing of soil, water and fish or of snails, daphnids, and algae by applying radioactive 14C-BHT (labelled with C at the phenyl carbons).

The bioconcentration factor (BCF) was determined in a model ecosystem under three different test conditions. After 28 days BCF values between 13 and 17 were found. However, the BCF values were derived from model ecosystems where adsorbant materials (soil) was present. There were only 2 fish in each experimental condition. It is not clear whether this test was performed in a flow-through system, and finally, degradation of the substance is not taken into account. With regard to the significant methodological deficiencies (test setup, low number of test animals), the study is regarded as not reliable (RL 3).

Experimental data

Reliability

Concentration level

BCF

MITI (1979)

2

5 µg/L

839 (range: 330 to 1800)

50 µg/L

1277 (range: 230 to 2500)

Inui et al. (1979)

3

unclear

>=13 to <= 17

 

In order to assess the bioaccumulation potential of BHT, QSAR models were used in a weight-of-evidence approach in combination with the experimental data. The estimated data are summarized in the table below:

Model

Reliability

Remark

BCF

BCFBAF v3.01 (EPI Suite v4.11)

2

within applicability domain (AD)

646

US EPA T.E.S.T. v4.1

4

within AD, however confidence is low

1656

VEGA v1.1.0 BCF model (KNN/Read-Across) v1.1.0

2

in AD, good reliability

1265

VEGA v1.1.0 BCF model (CAESAR) v2.1.13

2

in AD, good reliability

465

 

Based on the available data it can be concluded that BHT may be moderately accumulated in organisms; however, the majority of the BCF values (estimated and experimental) are below the critical value for bioaccumulative substances (BCF = 2000) according to REACH Annex XIII.

The BCF values > 2000 in the MITI study should be regarded as outliers which are not further supported.

As key value, the highest experimental BCF (mean value) was selected: BCF = 1277. This is a worst-case approach considering the available reliable data.