3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1)

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

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 limited documentation / justification

Justification for type of information:

Data is from OECD QSAR toolbox version 3.3 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox version 3.3.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1)
- Molecular formula: C40H52Cl4N6O2Zn
- Molecular weight: 856.093 g/mol
- Smiles notation: [o+]1c2cc(ccc2nc2ccc(N(CC)CC)cc12)N(CC)CC.[Zn+2].[ClH-].[ClH-].[ClH-].[ClH-].[o+]1c2cc(ccc2nc2c1cc(cc2)N(CC)CC)N(CC)CC
- InChl: 1S/2C20H26N3O.4ClH.Zn/c2*1-5-22(6-2)15-9-11-17-19(13-15)24-20-14-16(23(7-3)8-4)10-12-18(20)21-17;;;;;/h2*9-14H,5-8H2,1-4H3;4*1H;/q2*+1;;;;;+2/p-4
- Substance type: Organic
- Physical state:

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Test type:

static

Water media type:

freshwater

Total exposure duration:

96 h

Hardness:

350 mgCaCO3/L

Test temperature:

21°C

pH:

7.5-7.6

Dissolved oxygen:

8.6-8.8 mgO2/L

Reference substance (positive control):

not specified

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

0.928 mg/L

Nominal / measured:

estimated

Conc. based on:

not specified

Basis for effect:

mortality (fish)

Remarks on result:

other: Other details not known

Details on results:

The LC50 was 0.9281 mg/l for 96 hrs of exposure.

Sublethal observations / clinical signs:

The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((("a" or "b" or "c" )  and "d" )  and "e" )  and "f" )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and "p" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Zinc metal and salts by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Soluble complexes of Zinc by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as SHOULD NOT BE PROFILED by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acid moiety OR Amides OR Esters, Monothiophosphates OR Not Related to an Existing ECOSAR Class OR Salt OR Triazines, Aromatic by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Aromatic amine   [-NH2  or  -NH-] AND Aromatic-H AND -CH2-  [linear] AND Methyl  [-CH3] AND Number of fused 6-carbon aromatic rings AND Tertiary amine by Bioaccumulation - metabolism alerts

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring by Bioaccumulation - metabolism alerts

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Aromatic amine   [-NH2  or  -NH-] AND Aromatic-H AND -CH2-  [linear] AND Methyl  [-CH3] AND Number of fused 6-carbon aromatic rings AND Tertiary amine by Bioaccumulation - metabolism alerts

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as -CH2-  [cyclic] by Bioaccumulation - metabolism alerts

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aromatic amine   [-NH2  or  -NH-] AND Aromatic-H AND -CH2-  [linear] AND Methyl  [-CH3] AND Number of fused 6-carbon aromatic rings AND Tertiary amine by Bioaccumulation - metabolism alerts

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as No alert found by Bioaccumulation - metabolism alerts

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log BCF max which is >= 0.964 log(L/kg wet)

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log BCF max which is <= 3.33 log(L/kg wet)

Validity criteria fulfilled:

not specified

Conclusions:

Based on the mortality rate, LC50 value was estimated to be 0.9281 mg/l for Oncorhynchus mykiss (previous name: Salmo gairdneri) for 96hrs of duration. 

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on fish was predicted for the 96 h LC50 for 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS:63589-47-9). Based on the mortality rate, LC50 value was estimated to be 0.9281 mg/l for Oncorhynchus mykiss (previous name: Salmo gairdneri) for 96hrs of duration. 

Based on this value it can be concluded that the substance 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS:63589-47-9)is considered to be toxic to aquatic environment and classified in aquatic acute category 1 as well as chronic 1 as per the criteria mentioned in CLP regulation. 

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on fish was predicted forthe 96 h LC50 for 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS:63589-47-9). Based on the mortality rate, LC50 value was estimated to be 0.9281 mg/l for Oncorhynchus mykiss (previous name: Salmo gairdneri) for 96hrs of duration. Based on this value it can be concluded that the substance 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS:63589-47-9)is considered to be toxic to aquatic environment and classified in aquatic acute category 1 as well as chronic 1 as per the criteria mentioned in CLP regulation. 

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

0.928 mg/L

Additional information

Based on the various experimental data for the target chemical and prediction data for RA chemical which was selected on the basis of structure similarity study have been reviewed to determine the toxic nature of 3,7-bis(diethylamino)phenoxazin-5-iumtetrachloro- zincate (2:1) (63589-47-9) on the mortality of fish. The studies are as mentioned below:  

In the first predicted weight of evidence report for the 3,7-bis(diethylamino)phenoxazin-5-iumtetrachloro- zincate (2:1) (63589-47-9) from SSS (QSAR, 2017) toxicity study was carried out. Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on fish was predicted for the 96 h LC50 for 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS:63589-47-9). Based on the mortality rate, LC50 value was estimated to be 0.9281 mg/l for Oncorhynchus mykiss (previous name: Salmo gairdneri) for 96hrs of duration. Based on this value it can be concluded that the substance 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) (CAS:63589-47-9)is considered to be toxic to aquatic environment and classified in aquatic acute category 1 as well as chronic 1 as per the criteria mentioned in CLP.

 

Similarly the second prediction study was performed based on the prediction done by EPI suite, ECOSAR version 1.11, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program, the LC 50 value for short term toxicity to fish was predicted. On the basis of this programe, the LC 50 value for short term toxicity to fish was predicted to be 0.289 mg/l for 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) in 96 hrs. Based on this value it can be concluded that the substance 3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1) is considered to be toxic to aquatic environment and can be classified as aquatic acute category 1 as well as chronic 1 as per the criteria mentioned in CLP.

 

Similarly in the third weight of evidence study for the read across (548-62-9) (from Haskell Laboratory for Toxicology and Industrial Medicine, 1977) toxicity was conducted on fish to determine the toxic nature of chemical. Study was conducted to determine the effect of [4-[4,4'-bis(dimethylamino) benzhydrylidene]cyclohexa-2,5-dien-1-ylidene]dimethylammonium chloride on aquatic environment, [4-[4,4'-bis(dimethylamino)benzhydrylidene]cyclohexa -2,5-dien-1-ylidene]dimethylammonium chloride was exposed to Pimephales promel as for 96hr. Test performed according to the standard static system. 0.1 mg/ ml solution in distilled water was introduced into all glass vessels which contained 10 fathead minnows in 15 liters of water. Fishes were not fed for 48 hours prior to testing nor during exposure. No aeration was provided during the test and temperature was maintained at 20 ± 0.2 degC. After the exposure no distinct signs of toxicity were observed. Its 96-hour LC-50  is 0.082 mg/l with 95% confidence limits of 0.065 mg/l and 0.11 mg/l. The slope of the dose response curve is 4.55 with 95% confidence limits of 2.16 and 6.94. It ca be concluded that the 4-{bis[4 (dimethylamino) phenyl]methylidene}-N,N-dimethylcyclohexa-2,5-dien-1-iminium chloride is toxic to the aquatic environment and can be considered as aquatic acute category 1 as well as chronic 1 as per the criteria mentioned in CLP.

 

Similarly in the fourth weight of evidence study for the same read across chemical selected on the basis of structural and functional similarity basis (548-62-9) from The Journal of Toxicological Sciences, 1982. TLm (median tolerance limit) test was carried out according to the procedure of Japan Industrial Standards (Japanese Industrial Standards Committee, 1971). Ten fish of Himedaka per one trial were kept in 2 liter of deionized water at 25 degree C and, after 24 or 48 hours, lethal concentration of 50% fish was determined. The Lethal concentration to 50% of Oryzias latipes for 24 Hour under static condition is 0.2 mg/L and for 48 hr is 0.1 mg/L. It can be concluded that the [4-[4,4'-bis (dimethylamino) benzhydrylidene]cyclohexa-2,5-dien-1-ylidene] dimethylammonium chloride is toxic to the aquatic environment and can be considered as aquatic acute category 1 as well as chronic 1 as per the criteria mentioned in CLP.

Thus based on the above data sources for target chemical 3,7-bis(diethylamino)phenoxazin-5-iumtetrachloro- zincate (2:1) (63589-47-9) from various experimental studies and predicted studies from QSAR, EPIsuite, Haskell Laboratory for Toxicology and Industrial Medicine, 1977 and The Journal of Toxicological Sciences, 1982, it was summarized that the chemical was toxic to aquatic organisms and thus can be classified as aquatic acute category 1 as well as chronic 1 as per the criteria mentioned in CLP.