3,7-bis(diethylamino)phenoxazin-5-ium acetate

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:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3 with logKow as the primary descriptor.

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 acetate
- Molecular formula: C22H29N3O3
- Molecular weight: 383.489 g/mol
- Smiles notation: c1c2nc3ccc(cc3[o+]c2cc(N(CC)CC)c1)N(CC)CC.C(C)(=O)[O-]
- InChl: 1S/C20H26N3O.C2H4O2/c1-5-22(6-2)15-9-11-17-19(13-15)24-20-14-16(23(7-3)8-4)10-12-18(20)21-17;1-2(3)4/h9-14H,5-8H2,1-4H3;1H3,(H,3,4)/q+1;/p-1
- Substance type: Organic
- Physical state: Solid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Oryzias latipes

Test type:

semi-static

Water media type:

freshwater

Total exposure duration:

96 h

Hardness:

44.0 mg/L as CaCO3

Test temperature:

23.9 - 24.5 ºC

pH:

7.3 - 7.7

Dissolved oxygen:

7.2 - 8.4 mg/L

Reference substance (positive control):

not specified

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

0.839 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

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

Domain logical expression index: "a"

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: "b"

Referential boundary: The target chemical should be classified as Peroxy Acids by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> 2-Alken-1-als (MA) OR Highly reactive (GSH) >> Cinnamaldehydes (MA) by Protein binding potency

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Peroxy Acids by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Not Related to an Existing ECOSAR Class by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 4

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.28

Validity criteria fulfilled:

not specified

Conclusions:

The lethal concentration (LC50) value for chemical 3,7-bis(diethylamino)phenoxazin-5-ium acetate on Oryzias latipes in a 96 hour study was estimated to be 0.838 mg/L on the basis of effects on mortality.

Executive summary:

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 to fish was predicted for target substance 3,7-bis(diethylamino)phenoxazin-5-ium acetate (CAS no. 79916 -07 -7). LC50 value was estimated to be 0.838 mg/l for Oryzias latipes for 96 h duration. Based on this value it can be concluded that the substance 3,7-bis(diethylamino)phenoxazin-5-ium acetate is considered to be toxic to aquatic environment and can be considered to be classified in aquatic acute 1/ chronic 1

category as per the CLP classification criteria.

Description of key information

Using the OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity to fish was predicted for target substance 3,7-bis(diethylamino)phenoxazin-5-ium acetate (CAS no. 79916 -07 -7). LC50 value was estimated to be 0.838 mg/l for Oryzias latipes for 96 h duration. Based on this value it can be concluded that the substance 3,7-bis(diethylamino)phenoxazin-5-ium acetate is considered to be toxic to aquatic environment and can be considered to be classified in aquatic acute 1 / chronic 1 category as per the CLP classification criteria.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

0.838 mg/L

Additional information

Predicted data for the target chemical 3,7-bis(diethylamino)phenoxazin-5-ium acetate (CAS No. 79916-07-7) and various supporting weight of evidence studies for its closest read across substances with logKow as the primary descriptorwere reviewed to summarize the following information:

 

Short term toxicity on aquatic invertebrate of target chemical3,7-bis(diethylamino)phenoxazin-5-ium acetate(CAS No. 79916-07-7) is predicted using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances (2017). On the basis of effects observed in a semi-static freshwater system, the lethal concentration LC50 value for the substance is estimated to be 0.838 mg/L for Oryzias latipes for 96 hr duration.

 

In a weight of evidencestudy from authoritative database (J-CHECK, 2017) of the read across chemical (peroxybis(propane-2,2-diyl))dibenzene (CAS no. 80-43-3),short term toxicity to fish study was carried out for 96 hrs. The study was performed according to OECD Guideline 203 (Fish, Acute Toxicity Test). The study was based on the effects of the read across compound (peroxybis(propane-2,2-diyl))dibenzene on Oryzias latipes in a semi-static fresh water system at a temperature of 24 ± 1°C.Test chemical concentration used for the study were 2.00, 1.43, 1.02, 0.729, 0.521 mg/l (geometric ration 1.4). Analytical methods used for the study was HPLC. The study was performed in duplicates using5 organisms per vessels (10/concentration) under room light, 16 h light – 8 h dark. Based on effect on mortality of the test organism Oryzias latipes, the 96 hr LC50 value was determined to be 0.469 mg/l.

 

For the read across chemical 2-(diethylamino)-6-methylpyrimidin-4-yl methyl methoxy(sulfanylidene)phosphonite (CAS no. 29232-93-7), short term toxicity to fish (Oncorhynchus mykiss) study was carried out for 96 hrs (HSDB and ECOTOX database, 2017). The study was based on the effects of the read across compound 2-(diethylamino)-6-methylpyrimidin-4-yl methyl methoxy(sulfanylidene)phosphonite (CAS no. 29232 -93 -7) on Oncorhynchus mykiss in a flow through fresh water system. Oncorhynchus mykiss (Rainbow trout) was used as a test organism. Based on effect on mortality of the test organism Oncorhynchus mykiss, the 96 hr LC50 value was determined to be 0. 404 mg/l (95% C. I. = 0.36 to 0.44 mg/l), respectively.

 

Another short term toxicity to fish (Rutilus rutilus) study from authoritative database (ECOTOX database, 2017) was carried out for 96 hrs. The study was based on the effects of the read across compound 2-(diethylamino)-6-methylpyrimidin-4-yl methyl methoxy(sulfanylidene)phosphonite (CAS no. 29232-93-7) on Rutilus rutilus in a fresh water system. Rutilus rutilus (Roach) was used as a test organism. Based on effect on mortality of the test organism Rutilus rutilus, the 96 hr LC50 value was determined to be 0.84 mg/l, respectively.

 

Thus, based on the overall reported results for target chemical 3,7-bis(diethylamino)phenoxazin-5-ium acetate(OECD QSAR toolbox version 3.3, 2017) and for its read across substance (fromauthoritative database ECOTOX, HSDB and J-CHECK),it can be concluded that the test substance3,7-bis(diethylamino)phenoxazin-5-ium acetatecan be considered as toxic to aquatic fish and can be considered to be classified in aquatic acute 1/ chronic 1 category as per the CLP classification criteria.