1,8-bis[(4-methylphenyl)amino]anthraquinone

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

Justification Document for the Category of Six Anthraquinone Dyes

LANXESS Deutschland GmbH has registered five mono-constituent anthraquinone dyes of similar chemical structure using a category approach: Solvent Violet 36 (CAS No 82-16-6), Solvent Green 3 (CAS No 128-80-3), Reinblau RLW (CAS No 41611-76-1), Reinblau BLW (CAS No 32724-62-2) and Solvent Green 28 (CAS No 4851-50-7). Additional data were taken from another registered anthraquinone dye, Solvent Blue 104 (CAS No 116-75-6), leading to a category consisting of six members (see attached justification in the Category dossier in section 13).

Test organisms (species):

Cyprinus carpio

Route of exposure:

feed

Type:

BCF

Value:

2 - 5 dimensionless

Basis:

whole body w.w.

Remarks on result:

other: The concentration of the test substance in fish ranged from 0.37 to 1.08 µg/g (w/w).

Remarks:

Conc.in environment / dose:0.2 µg/ml

Details on results:

No mortality was observed during the exposure period of 4 weeks. Therefore, it was confirmed that the test fish had been reared appropriately:
- Condition of fish: There was no abnormality in shape of the body or in swimming and feeding behavior
- Body weight: 21.32-29.41 g
- Total length: 9.5-10.6 cm
- Fat content: 4.4% (n=4, 4.0-4.9%)

Validity criteria fulfilled:

yes

Conclusions:

The concentration of the source substance in fish ranged from 0.37 to 1.08 µg/g (w/w) and the bioconcentration (BCF) was 2 to 5. On the basis of the BCF obtained, it is concluded that the bioaccumulation potential of the source substance in fish is low under the test condition. The results refere to the structure related 1,4-bis(2-ethyl-6-methy1anilino) anthraquinone (CAS-No. 41611-76-1) of 1,8-bis[(4-methylphenyl)amino]-9,10-anthraquinone (CAS-No 82-16-6).

Executive summary:

The simplified study for 4 weeks with one exposure level was conducted in reference to the Test Method Relating to New Chemical Substauces (Kanpogyo No.5, Yakuhatsu No.615, 49 Kikyoku No.392, 1974, amended I 998), which is equivalent to the OECD Guideline 305. The bioconcentration test system was set up in duplicate. One group of carp was set as the control, another group was exposed to the Reinblau RLW (CAS n° 41611-76-1). During the exposure period, the concentrations of the test substance in water and fish were measured periodically. The bioconcentration factors (BCF) calculated from the results were used to evaluate the bioaccumulative potential of the test substance in tissues of carp. Prior to the bioconcentration test, an acute toxicity test was conducted with Medaka and 50% lethal concentration (LC5O) was determined. The bioconcentration test was carried out at the exposure level not exceeding a hundredth of the 48hour LC50 (85 µg/ml). The concentration of the test substance in fish ranged from 0.37 to 1.08 µg/g (w/w) and the bioconcentration (BCF) was 2 to 5.

Based on category approach, the target substance, C.I. Solvent Violet 36 (1,8-bis[(4-methylphenyl)amino]-9,10-anthraquinone; CAS-No. 82-16-6) has a low potential of bioaccumulation.

Reference 2

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

supporting 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
Individual model BCFBAF included in the Estimation Programs Interface (EPI) Suite.

2. MODEL (incl. version number)
BCFBAF v3.01 included in EPISuite v 4.11, 2000 - 2012

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
The CAS NUMBER was entered in the initial data entry screen. An experimental determined log Kow value was provided prior to estimation.
A searchable database of CAS RNs and corresponding SMILES structures are provided within the KOWWIN program. CAS RNs are available for approximately 112,000 organic chemicals. If a CAS RN is not available, a SMILES notation can be directly entered by the user. Alternatively, logKow values can be manually entered if available. The correction factors are linked to the presence of certain structural fragments or functional groups.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
a. Defined endpoint: Bioconcentration factor (BCF). As a coefficient the logBCF is given without unit. The BCF can be given with L/kg wet wt.
b. Explicit algorithm (OECD Principle 2): The BCF is usually estimated from regression equations of the general form logBCF= a logKow + b, whereas a and b are empirically determined constants and Kow is the n octanol/water partition coefficient. Therefore, logBCF values for the non-ionic and ionics were plotted separately against the respective logKow values yielding a linear relationship for certain logKow ranges. Furthermore, compounds sharing certain structural features were identified resulting in residuals that were relatively consistent in sing and magnitude. On this basis several compound classes were identified that seemed amenable to derivation of correction factors.

Non-ionic compounds:
(i) For LogKow 1.0 to 7.0 the derived QSAR estimation equation is:
Log BCF= 0.6598 LogKow - 0.333 + Σ correction factors
(ii) For LogKow > 7.0 the derived QSAR estimation equation is:
Log BCF= -0.49 LogKow + 7.554 + Σ correction factors
(iii) For LogKow < 1.0 the derived QSAR estimation equation is:
All compounds with a logKow of less than 1.0 are assigned an estimated log BCF of 0.50.

Ionic compounds:
logKow < 5.0: log BCF= 0.50
logKow 5.0 to 6.0: log BCF= 0.75
logKow 6.0 to 7.0: log BCF= 1.75
logKow 7.0 to 9.0: log BCF= 1.00
logKow > 9.0: log BCF= 0.50

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.
Metals (tin and mercury), long chain alkyls and aromatic azo compounds require special treatment (see Meylan et al., 1999).
For ionic substances with long alkyl chains (≥ 11 carbons) a general log BCF of 1.85 was assigned by the program.

c. Applicability domain: The minimum and maximum values for molecular weight are the following:
Training Set Molecular Weight:
Minimum MW (Non-Ionic): 68.08
Maximum MW (Non-Ionic): 959.17
Average MW (Non-Ionic): 513.63

Minimum MW (Ionic): 102.13
Maximum MW (Ionic): 991.80
Average MW (Ionic): 546.97

The minimum and maximum values for logKow are the following:
Training Set logKow:
Minimum LogKow (Non-Ionic): -1.37
Maximum LogKow (Non-Ionic): 11.26

Minimum LogKow (Ionic): -6.50
Maximum LogKow (Ionic): 7.86

d. Statistics for goodness-of-fit:
number in dataset = 527
correlation coef (r^2) = 0.833
standard deviation = 0.502
average deviation = 0.382

e. Predictivity – Statistics obtained by external validation:
number in dataset = 158
correlation coef (r2) = 0.82
standard deviation = 0.59
average deviation = 0.46

f. Mechanistic interpretation: The BCF is an inherent property used to describe the accumulation of a substance dissolved in water by an aquatic organism. The BCFBAF program estimates BCF of an organic compound using the compound's log octanol-water partition coefficient (Kow).
Measured BCFs and other experimental details were collected and analysed to derive subsets of data on non-ionic, ionic, aromatic and azo compounds, tin and mercury compounds. Because of the deviation from rectilinearity, different models were developed for different log Kow ranges, and a set of 12 correction factors and rules were introduced to improve the accuracy of the BCF predictions.

g. The uncertainty of the prediction (OECD principle 4): The rules applied for estimating the BCF of solvent violet 36 appear appropriate. An individual uncertainty for the investigated substance is not available.

h. The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5): Not applicable.

i. Limits of applicability: Model predictions may be highly uncertain for chemicals that have estimated log KOW values > 9. The model is not recommended at this time for chemicals that appreciably ionize, for pigments and dyes, or for perfluorinated substances.

5. APPLICABILITY DOMAIN
a. Descriptor Domains:
i. log Kow: With a log Kow value of 8.3, the substance is within the range of the training set (Non-Ionics: -1.37 – 11.26).
ii. Molecular weight: With a molecular weight of 418.49 g/mole the substance is within the range of the training set (Non-Ionics 68.08 – 959.17).
iii. Structural fragment domain: Not applicable as the BCF is not estimated on the basis of fragments.
iv. Mechanism domain: NO INFORMATION AVAILABLE
v. Metabolic domain: NOT RELEVANT
b. Structural analogues: Not relevant as the BCF is not estimated based on structural fragments.

6. ADEQUACY OF THE RESULT
a. Regulatory purpose: The data may be used for regulatory purpose.
b. Approach for regulatory interpretation of the model result: If no experimental data are available, the estimated value may be used to fill data gaps needed for hazard and risk assessment.
c. Outcome: The estimation of the bioconcentration factor (BCF) yields a useful result for further evaluation.
d. Conclusion: The result is considered as useful for regulatory purposes.

Guideline:

other: REACH guidance on QSARs R.6, May 2008

Deviations:

not applicable

Principles of method if other than guideline:

Calculated with BCF Program BCFBAF v.3.01 included in the Estimation Programs Interface (EPI)-Suite. The estimation methodology is based on the chemical structure of an organic compound and its log octanol-water partition coefficient (log Kow). Depending on chemical structure, structural correction factors are applied.

GLP compliance:

no

Radiolabelling:

no

Test organisms (species):

other: none, estimated by calculation

Type:

BCF

Value:

797.8 L/kg

Basis:

other: calculation

Any decomposition of the substance in water is not considered by the program.

Validity of model:

- Defined endpoint: bioconcentration of a substance in biota

- Unambiguous algorithm: linear regression QSAR. Because of the deviation from rectilinearity, different models were developed for different log Kow ranges. Metals (tin and mercury), long chain alkyls and aromatic azo compounds are specially treated.

- Applicability domain: the model is applicable to ionic as well as non-ionic compounds. It is applicable to substances with a logKow in the following range: -6.50 to 7.86 (ionic compounds) and -1.37 to 11.26 (non-ionic compounds). Applicable to substances with a molecular weight in the following range: 102.13 to 991.80 g/mole (ionic substances) and 68.08 and 959.17 g/mole (non-ionic compounds). ). Model predictions may be highly uncertain for chemicals that have estimated logKow values > 9. The model is not recommended at this time for chemicals that appreciably ionize, for pigments and dyes, or for perfluorinated substances.

- Statistical characteristics:

number in dataset = 527

correlation coef (r2) = 0.833

standard deviation = 0.502

- Mechanistic interpretation: The BCF is an inherent property used to describe the accumulation of a substance dissolved in water by an aquatic organism based on the lipophilicity of the compound.

Adequacy of prediction: Solvent Violet 36 falls within the applicability domain described above and, therefore, the predicted value can be considered reliable taking into account that the standard deviation error of prediction of the external test set is 0.59 (logBCF). Considering that error, the predicted value is not above or close to the criterion to consider a substance as potential bioaccumulative.

Conclusions:

The bioaccumulation factor (BCF) of Solvent Violet 36 was estimated to be 798 L/kg wet-wt sing the BCFBAF model included in the EPI-Suite Programm concluding that the substance has a moderate potential to bioaccumulate in biota.

Executive summary:

The bioaccumulation factor (BCF) of Solvent Violet 36 was estimated to be 798 L/kg wet-wt sing the BCFBAF model included in the EPI-Suite Programm concluding that the substance has a moderate potential to bioaccumulate in biota.

Within the scope of the Persistency-Bioaccumulation-Toxicity (PBT)-Assessment, the substance does not fullfil the B-criterion.

Solvent Violet 36 falls within the applicability domain described above and, therefore, the predicted value can be considered reliable.

Description of key information

Read-Across on Reinblau RLW, Key, Rel 2 ; Test Method Relating to New Chemical Substances (Kanpogyo No.5, Yakuhatsu No.615, 49 Kikyoku No.392, 1974, amended 1998)/similar to OECD 305; Mitsubishi (2011): BCF=2-5

On the basis of the BCF obtained and category approach, it is concluded that the bioaccumulation potential of the Violet 36 (CAS n°82-16-6) in fish is low under the test condition.

 

 

Key value for chemical safety assessment

BCF (aquatic species):

5 L/kg ww

Additional information

Additional information:

Key value: "Should read: BCF= 2 - 5": As the test substance has a very low water solubility HCO-30 was used as solubilizer in the test system. If possible no solubilizer should be applied to the test system. But as the results for the BCF are very small and the usage of a solubilizer is increasing the concentration of the test substance in the test system, the present result can be used as a worst case displaying a very low bioaccumulation potential for the substance under environmentally relevant conditions.

Supporting result: QSAR data is available on C.I Solvent Violet 36, the bioaccumulation factor (BCF)  was estimated to be 798 L/kg wet-wt using the BCFBAF model included in the EPI-Suite Program concluding that the substance is not considered bioaccumulative.

Category approach:

LANXESS Deutschland GmbH has registered five mono-constituent anthraquinone dyes of similar chemical structure using a category approach: Solvent Violet 36 (CAS No 82-16-6), Solvent Green 28 (CAS No 4851-50-7), Reinblau RLW (CAS No 41611-76-1), Reinblau BLW (CAS No 32724-62-2) and Solvent Green 3 (CAS No 128-80-3). Additional data were taken from another registered anthraquinone dye, Solvent Blue 104 (CAS 116 -75 -6), leading to a category consisting of six members (see attached justification in IUCLID chapter 13). The category consists of substances all having the diamino-anthraquinone structure as a common moiety which is linked to phenyl groups via the amino groups. Differences within the category are described by various alkyl groups bound to the phenyl groups. All substances included in the category approach are poorly water soluble with high adsorption coefficient (log Koc>6), high partition coefficient (logKow>8) and not readily biodegradable.

Data available on other members of the category confirmed the low bioaccumulation of the substances:

Reinblau RLW (CAS n°41611-76-1)	similar to OECD 305	BCF= 2-5 L/kg
Reinblau RLW (CAS n°41611-76-1)	QSAR (EPI) Suite V4.11 - BCFBAF v3.01	BCF= 569 L/kg
Reinblau BLW (CAS n°32724-62-2)	QSAR (EPI) Suite V4.11 - BCFBAF v3.01	BCF= 4.76 L/kg
Green 28 (CAS n° 4851-50-7)	QSAR (EPI) Suite V4.11 - BCFBAF v3.01	BCF= 53 L/kg
Blue 104 (CAS n°116-75-6)	QSAR (EPI) Suite V4.11 - BCFBAF v3.01	BCF= 405.4 L/kg
Green 3 (CAS n°128-80-3)	QSAR (EPI) Suite V4.11 - BCFBAF v3.01	BCF= 893 L/kg