2-(4,6-bis-(2,4-dimethylphenyl)-1,3,5-triazin-2-yl)-5-(octyloxy)-phenol

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

key study

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: BCFBAF, part of Estimation Programs Interface SuiteTM (EPI Suite) for Microsoft® Windows, v 4.11

2.MODEL (incl. version number): BCFBAF - Estimation of Bioconcentration Factor (BCF)

3.SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL:
Structural formula: C33H39N3O2
Structural codes:
a.SMILES: Cc4ccc(c1nc(nc(n1)c2ccc(cc2O)OCCCCCCCC)c3ccc(C)cc3C)c(C)c4
b.InChI: InChI=1S/C33H39N3O2/c1-6-7-8-9-10-11-18-38-26-14-17-29(30(37)21-26)33-35-31(27-15-12-22(2)19-24(27)4)34-32(36-33)28-16-13-23(3)20-25(28)5/h12-17,19-21,37H,6-11,18H2,1-5H3

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Bioconcentration (BCF) in fish
- Unambiguous algorithm: Linear regression - The BCFBAF method classifies a compound as either ionic or non-ionic. Ionic compounds include carboxylic acids, sulfonic acids and salts of sulfonic acids, and charged nitrogen compounds (nitrogen with a +5 valence such as quaternary ammonium compounds). All other compounds are classified as non-ionic. Methodology for Non-Ionic was to separate compounds into three divisions by Log Kow value as follows: LogKow<1.0, LogKow 1.0 to 7.0, LogKow>7.0. For each division, a "best-fit" straight line was derived by common statistical regression methodology. The regression methodology includes derivation of correction factors based on specific structural features. More details, including model equations, are provided in the attached QMRF.
- Defined domain of applicability: Detailed structural and/or response limits of the applicability domain are not defined, however the MW and LogKow ranges of the training set compounds were considered to define limits for the applicability domain of the model, as follows:
Molecular Weight - Minimum MW: 68.0; Maximum MW: 991.80 and 959.17 for Ionic and Non-ionic chemicals, respectively.
Log Kow - Maximum LogKow: 11.26; Minimum LogKow: -6.50 and -1.37 for Ionic and Non-ionic chemicals, respectively.
- Appropriate measures of goodness-of-fit and robustness and predictivity: Please see attached QMRF.
- Mechanistic interpretation: The BCF is defined as the ratio of the chemical concentration in the whole organism and the chemical concentration in the water at steady state. The distribution of the chemical among the different tissues of an organism can also be influenced by the lipid contents of the tissues (Arnot and Gobas 2006), and Kow and bioconcentration factor relationships are largely a reflection of chemical accumulation in fat (Bertelsen et al. 2009). Overall, there is a strong statistically significant positive correlation of LogBCF with LogKow for substances with LogKow greater than zero. Whereas, there is no apparent relationship between LogBCF and LogKow for chemicals with LogKow less than zero.

5.APPLICABILITY DOMAIN
The target compound 2-[4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-(octyloxy)phenol is included in the model applicability domain since the MW and LogKow of the target are within the MW and LogKow ranges of the training set chemicals.
- Descriptor domain: LogKow of the target (experimental LogKow = 4.84) is included in the LogKow range of the training set of chemicals (LogKow range: -1.37 ÷ 11.26 for non-ionic chemicals).
- Structural domain: the “aromatic sym-triazine ring” and the “alkyl chains (8+ - CH2-groups)” correction factors have been applied to the model equation. The occurrence of these fragments in the target molecule was equal or below the maximum number of each factor in any individual compound of the training set.
- Mechanistic domain: not applicable.
- Similarity with analogues in the training set: No structural analogues from the training set are provided by BCFBAF estimation program.

6. ADEQUACY OF THE RESULT
The LogBCF prediction of 0.969 (corresponding to a BCF equal to 9.316 L/kg) was estimated for the target 2-[4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-(octyloxy)phenol (CAS No. 2725-22-6). The prediction was assessed as moderately reliable.

Qualifier:

according to guideline

Guideline:

other:

Version / remarks:

REACH Guidance on QSARs R.6 (2008)

Principles of method if other than guideline:

- Software tool(s) used including version: BCFBAF, part of Estimation Programs Interface SuiteTM
(EPI Suite) for Microsoft® Windows, v 4.11
- Model(s) used: BCFBAF - Estimation of Bioconcentration Factor (BCF)
- Model description: see field 'Justification for type of information' and 'Attached justification'
- Justification of QSAR prediction: see field 'Justification for type of information' and 'Attached
justification'

Specific details on test material used for the study:

SMILES: Cc4ccc(c1nc(nc(n1)c2ccc(cc2O)OCCCCCCCC)c3ccc(C)cc3C)c(C)c4

Type:

BCF

Value:

9.316 L/kg

Details on results:

The LogBCF prediction of 0.969 (corresponding to a BCF equal to 9.316 L/kg) was estimated for the target 2-[4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-(octyloxy)phenol (CAS No. 2725-22-6).
The QSAR prediction was assessed as moderately reliable due to limited uncertainty based on the following considerations:
- scientific validity of the QSAR model: overall good prediction accuracy of the BCF estimation method (R2TR = 0.83, n = 527; R2V = 0.82, n = 158). In more detail, good prediction accuracy of the BCF estimation method for non-ionic compounds with LogKow values in the range 1 ÷ 7 (R2TR = 0.79, Q2TR = 0.78, n = 396).
- applicability domain: the 2-[4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-(octyloxy)phenol is included in the applicability domain of the model.

Conclusions:

The LogBCF prediction of 0.969 (corresponding to a BCF equal to 9.316 L/kg) was estimated for the target 2-[4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-(octyloxy)phenol (CAS No. 2725-22-6). The prediction was assessed as moderately reliable.

Executive summary:

This study was designed to generate estimated in silico (non-testing) bioconcentration factor (BCF) values in fish for 2-[4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-(octyloxy)phenol. A reliability score of 2 was assigned, since results were derived from a valid QSAR model with adequate and reliable documentation/justification. The bioconcentration factor (BCF) of the compound was estimated employing the BCFBAF estimation program, implemented in EPI Suite, which provides BCF estimations based on LogKow and correction factors for specific structural features.

A LogBCF prediction of 0.969 (corresponding to a BCF equal to 9.316 L/kg) was obtained. BCF estimations for the target were based on the non-ionic equations for compounds having a LogKow value in the range 1 – 7. Two correction factors were also identified in the target compound, and thus included in the model equation. The QSAR prediction was assessed as moderately reliable due to limited uncertainty based on the following considerations: 1) scientific validity of the QSAR model: overall good prediction accuracy of the BCF estimation method (R2TR = 0.83, n = 527; R2V = 0.82, n = 158). In more detail, good prediction accuracy of the BCF estimation method for non-ionic compounds with LogKow values in the range 1 ÷ 7 (R2TR = 0.79, Q2TR = 0.78, n = 396); 2) applicability domain: the 2-[4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-(octyloxy)phenol is included in the AD of the model.

Overall, the LogBCF QSAR prediction was assessed as adequate for regulatory purposes.

Reference 2

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Qualifier:

according to guideline

Guideline:

other: Concentration test of chemical substances in fish body" described in "On test methods of new chemical substancse" in regulations (Kanpogyo No.5, Yakuhatsu No.615, 49 Kikyoku No.392) issued on July 13, 1974

Principles of method if other than guideline:

At the purchase of the fish, abnormal fish were visually inspected and were removed; after drug bath in the reception tank, (the remaining) fish were maintained for 2 daysin flowing water. "Drug bath": It was carried out in still water for 24 hours using the solution containing reramycin powder for fishery at 50 mg/L and sodium chloride at 7 g/L.
We used a flow system built in the lab. Glass tank had a volume of 100 L volume. Test temperature: 25+/-2°C. Number of fish tested: 15 (start of exposure) for the 1st and 2nd test concentration. Control: 5 (start of exposure).
Duration of exposure: 8 weeks., place of exposure: second aquatron room.
Tests concentration: 0.5 mg/L and 0.05 mg/L.
Number of analysis: Test solution was analyzed twice every week with the total of 16 times using one sample in 1 analysis during period of exposure for both tests concentrations. Analysis of fish tested was carried out 4 times at 2, 4, 6 and 8 weeks after the start of exposure. Analysis was carried out before and after exposure in control using 2 fish for 1 analysis.

GLP compliance:

yes

Vehicle:

yes

Test organisms (species):

Cyprinus carpio

Details on test organisms:

Source: Sugishima fishery, 123-2, Tsuki-Ichiban-cho, Yatsushiro-shi, Kumamoto-ken 866

Route of exposure:

aqueous

Justification for method:

aqueous exposure method used for following reason: test substance soluble in water

Remarks:

/

Test type:

flow-through

Validity criteria fulfilled:

yes

Conclusions:

The BCF value calculated was more than 1 and less than 100 using the method of JIS Z 8401 -1961. Therefore, the substance is considered not to be bio-accumulative under these conditions of manipulations.

Executive summary:

The objective of this test is to to obtain information on concentration of the test substance in the carp (Cyprinus carpio). The test has been performed according to the "Concentration test of chemical substances in fish body" described in "On test methods of new chemical substancse" in regulations (Kanpogyo No.5, Yakuhatsu No.615, 49 Kikyoku No.392) issued on July 13, 1974.

The LC 50 for 48 h exposure: 300 mg/L or higher.

Concentration as ratio: The first test concentration: 0.3 times or less - 15 times. The second test concentration: 2.5 times or less - 5.1 times.

The BCF value calculated was more than 1 and less than 100 using the method of JIS Z 8401-1961. Therefore, the substance is considered not to be bio-accumulative under these conditions of manipulations.

Description of key information

Bioaccumulation of the substance was assessed in silico and in vivo in the fish. Both tests type indicate that the substance is not bioaccumulative. That is why there is no reason to classify the substance as H413.