Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: 

Based on the prediction done by SSS (2017) on 3,7-bis(diethylamino)phenoxazin-5-ium acetate, LD50 was estimated to be 707 mg/kg bw, when Wistar female rats were treated with 3,7-bis(diethylamino)phenoxazin-5-ium acetate via oral gavage route. Thus, comparing this value with the criteria of CLP regulation, 3,7-bis(diethylamino)phenoxazin-5-ium acetate can be classified as category IV for acute oral toxicity.

Acute Inhalation toxicity: 

Based on the prediction done by SSS (2017) on 3,7-bis(diethylamino)phenoxazin-5-ium acetate, LC50 was estimated to be 6.67 mg/L air, when male/female rats were exposed with 3,7-bis(diethylamino)phenoxazin-5-ium acetate for 7 h of exposure period. Thus, comparing this value with the criteria of CLP regulation, 3,7-bis(diethylamino)phenoxazin-5-ium acetate can be classified as category V for acute inhalation toxicity.

Acute Dermal toxicity: 

Based on the prediction done by SSS (2017) on 3,7-bis(diethylamino)phenoxazin-5-ium acetate, LD50 was estimated to be 5135 mg/kg bw, when New Zealand White male rabbit was treated with 3,7-bis(diethylamino)phenoxazin-5-ium acetate by dermal application. Thus, comparing this value with the criteria of CLP regulation, 3,7-bis(diethylamino) phenoxazin-5-ium acetate can be classified as category V for acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
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 predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached
Qualifier:
according to
Guideline:
other: estimated
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
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
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
not specified
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
not specified
Doses:
707 mg/kg
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
not specified
Statistics:
not specified
Preliminary study:
not specified
Sex:
female
Dose descriptor:
LD50
Effect level:
707 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality observed
Mortality:
not specified
Clinical signs:
not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified

The prediction was based on dataset comprised from the following descriptors: LD50
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 ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and "n" )  and "o" )  and "p" )  and "q" )  and ("r" and ( not "s") )  )  and ("t" and "u" )  )

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 Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Peroxides by US-EPA New Chemical Categories

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Substituted Triazines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Phenols (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Esters (Acute toxicity) OR Hindered Amines by US-EPA New Chemical Categories

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aldehydes (Acute toxicity) OR Aliphatic Amines OR Boron Compounds by US-EPA New Chemical Categories

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Acetoxy AND Aromatic amine AND Aryl AND Carboxylic acid AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic by Organic Functional groups ONLY

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acetoxy AND Aromatic amine AND Aryl AND Carboxylic acid AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic by Organic Functional groups ONLY

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Acetoxy AND Aromatic amine AND Aryl AND Carboxylic acid AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic by Organic Functional groups ONLY

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Acetoxy AND Aromatic amine AND Aryl AND Carboxylic acid AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic by Organic Functional groups ONLY

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Acetoxy AND Aromatic amine AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic AND Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Anilines (Hemolytic anemia with methemoglobinemia) Rank A by Repeated dose (HESS)

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 8.87

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
LD50 was estimated to be 707 mg/kg bw when Wistar female rats were treated with 3,7-bis(diethylamino)phenoxazin-5-ium acetate via oral gavage route.
Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for  3,7-bis(diethylamino)phenoxazin-5-ium acetate ( 79916-07-7). The LD50 was estimated to be 707 mg/kg bw when Wistar female rats were treated with 3,7-bis(diethylamino)phenoxazin-5-ium acetate via oral gavage route.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
707 mg/kg bw
Quality of whole database:
Data is Klimicsh 2 and from QSAR toolbox 3.3

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
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 predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached
Qualifier:
according to
Guideline:
other: estimated
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
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
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
not specified
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Remark on MMAD/GSD:
not specified
Details on inhalation exposure:
not specified
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
7 h
Remarks on duration:
not specified
Concentrations:
6.67 mg/L air
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
not specified
Statistics:
not specified
Preliminary study:
not specified
Sex:
male/female
Dose descriptor:
LC50
Effect level:
6.67 mg/L air
Based on:
test mat.
Remarks on result:
other: 50% mortality observed
Mortality:
not specified
Clinical signs:
other: not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified

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 "f" )  )

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-Metals by Groups of elements

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alkali Earth by Groups of elements

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.932

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is <= 8.87

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
LC50 was estimated to be 6.67 mg/L air, when male/female rats were exposed with 3,7-bis(diethylamino)phenoxazin-5-ium acetate for 7 h of exposure period.
Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for 3,7-bis(diethylamino)phenoxazin-5-ium acetate (79916 -07 -7). The LC50 was estimated to be 6.67 mg/L air, when male/female rats were exposed with 3,7-bis(diethylamino)phenoxazin-5-ium acetate for 7 h of exposure period.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
104.62 mg/m³
Quality of whole database:
Data is Klimisch 2 and QSAR toolbox 3.3.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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 predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached
Qualifier:
according to
Guideline:
other: estimated
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
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
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
not specified
Type of coverage:
not specified
Vehicle:
not specified
Details on dermal exposure:
not specified
Duration of exposure:
not specified
Doses:
5135 mg/kg
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
not specified
Statistics:
not specified
Preliminary study:
not specified
Sex:
male
Dose descriptor:
LD50
Effect level:
5 135 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality observed
Mortality:
not specified
Clinical signs:
not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((("a" or "b" )  and "c" )  and ("d" and ( not "e") )  )  and ("f" and "g" )  )

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 No alert found by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Alkali Earth by Groups of elements

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.58

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.46

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
LD50 was estimated to be 5135 mg/kg bw, when New Zealand White male rabbit was treated with 3,7-bis(diethylamino)phenoxazin-5-ium acetate by dermal application.
Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for  3,7-bis(diethylamino)phenoxazin-5-ium acetate ( 79916-07-7). The LD50 was estimated to be 5135 mg/kg bw, when New Zealand White male rabbit was treated with 3,7-bis(diethylamino)phenoxazin-5-ium acetate by dermal application.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 135 mg/kg bw
Quality of whole database:
Data is Klimicsh 2 and from QSAR toolbox 3.3

Additional information

Acute oral toxicity:

In different studies, 3,7-bis(diethylamino)phenoxazin-5-ium acetate (79916-07-7) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats and mice for 3,7-bis(diethylamino)phenoxazin-5-ium acetate along with the study available on structurally similar read across substance Rhodamine B (CAS no: 81-88-9) and 7-(diethylamino)-4-methyl-2-benzopyrone (CAS no: 91-44-1). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for  3,7-bis(diethylamino) phenoxazin-5-ium acetate ( 79916-07-7). The LD50 was estimated to be 707 mg/kg bw when Wistar female rats were treated with 3,7-bis(diethylamino)phenoxazin-5-ium acetate via oral gavage route.

The above study supported by P.L Smart (The NSS Bulletin 21-33, 1984), for the structurally similar read across substance Rhodamine B (CAS no: 81-88-9).The acute oral toxicity was tested in rats at the concentration of 500 mg/kg orally. No mortality observed in treated rats. Therefore, LD50 was considered to be > 500 mg/kg when rats were treated with rhodamine B orally.

This study is further supported by U.S. National Library of Medicine (ChemIDplus, 2017) and Review of the toxicology of a number of dyes illegally present in food in the EU, The EFSA Journal, 263, 1-71 (2005), for the structurally similar read across substance Rhodamine B (CAS no: 81-88-9). The acute oral toxicity was tested in mice at the dose concentration of 887 mg/kg bw. 50% mortality was observed at 887 mg/kg. Therefore, LD50 was considered to be 887mg/kg bw, when mice were treated with Rhodamine B via oral route.

In another study conducted by U.S. National Library of Medicine (ChemIDplus, 2017), for the structurally similar read across substance 7-(diethylamino)-4-methyl-2-benzopyrone (CAS no: 91-44-1).The acute oral toxicity was tested in mice at the dose concentration of 1780 mg/kg bw. 50% mortality was observed with behavioral changes such as, Somnolence (General Depressed Activity) in tested animals at 1780 mg/kg. Therefore, LD50 was considered to be 1780 mg/kg bw, when mice were treated with 7-(diethylamino)-4-methyl-2-benzopyrone via oral route.

Thus, based on the above studies on 3,7-bis(diethylamino)phenoxazin-5-ium acetate (79916-07-7) and it’s read across substances, it can be concluded that LD50 value is between 300 - 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 3,7-bis(diethylamino)phenoxazin-5-ium acetate can be classified as category IV of acute oral toxicity.

Acute Inhalation toxicity: 

In different studies, 3,7-bis(diethylamino)phenoxazin-5-ium acetate (79916-07-7) has been investigated for acute inhalation toxicity to a greater or lesser extent. Often are the studies conducted most commonly on human and rodents like rats and mice for 3,7-bis(diethylamino) phenoxazin-5-ium acetate along with the study available

on structurally similar read across substanceRhodamine B (81-88-9) andclosely related read across substance 2-Butanone, peroxide (CAS no: 1338-23-4). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for 3,7-bis(diethylamino) phenoxazin-5-ium acetate (79916 -07 -7). The LC50 was estimated to be 6.67 mg/L air, when male/female rats were exposed with 3,7-bis(diethylamino)phenoxazin-5-ium acetate for 7 h of exposure period.

The above study is supported by Danielet al(CLINICAL TOXICOLOGY, 25 (7), 603-60, 1987), for the structurally similar read across substanceRhodamine B (81-88-9).Approximately 10 lbs=4.53kg of Rhodamine B powder was spilled onto the floor of a vehicle maintenance shop. A cleanup crew began to sweep up the powder from the floor. This resulted in an aerosol of Rhodamine B dust that dispersed throughout the building contaminating the hair, skin, eyes, and clothing of most of the shop employees. 16 out of 17 of the patients (94%) complained of symptoms such as - One patient (6%) denied any symptoms despite being exposed to the dust for 15 minutes without a surgical mask. The most frequently reported symptom was burning of the eyes which occurred in 83% of the patients. Four of the patients (24%) were placed on humidified oxygen because of respiratory symptoms. Five o f the patients (29%) underwent irrigation of their eyes secondary to eye burning. After being discharged from the hospital and follow up is maintained. Ten of the patients (59%) reported that their symptoms had resolved within 4 hours of their exposure to the dust. One patient (6%) reported that his symptoms lasted 12 hours and 2 patients (12%) reported their symptoms lasted 24 hours. Three of the patients (18%) could not remember the duration of their symptoms. No serious effects observed .Based on this the Effect concentration could be reported as approx (4.53kg) 4530000mg.

These results are further supported by U.S. National Library of Medicine (ChemIDplus, 2017), for the closely related read across substance 2-Butanone, peroxide (CAS no: 1338-23-4). The acute inhalation toxicity study was conducted in mice at the concentration of170 ppm. 50% mortality was observed with clinical Symptoms like dyspnea and changes in lungs, thorax was observed at 170 ppm, when exposed for 4 hours. Therefore, LC50 was considered to be170 ppm (1461.68 mg/m3) when mice were treated with 2-Butanone, peroxide by inhalation for 4 hours.

Thus, based on the above studies on 3,7-bis(diethylamino)phenoxazin-5-ium acetate (79916-07-7) and it’s read across substances, it can be concluded that LC50 value is greater than 5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, 3,7-bis(diethylamino)phenoxazin-5-ium acetate can be classified as category V of acute inhalation toxicity.

Acute Dermal toxicity:

In different studies, 3,7-bis(diethylamino)phenoxazin-5-ium acetate (79916-07-7) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats and rabbits for 3,7-bis(diethylamino)phenoxazin-5-ium acetate along with the study available on closely related read across substance Disodium 4,4'-bis[(4-anilino-6-morpholino-1,3,5-triazin-2-yl)amino]stilbene-2,2'-disulphonate (16090-02-1) and Disodium 4,4'-bis[[6-anilino-4-[(2-hydroxyethyl)methylamino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate (13863-31-5). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for  3,7-bis(diethylamino) phenoxazin-5-ium acetate (79916-07-7). The LD50 was estimated to be 5135 mg/kg bw, when New Zealand White male rabbit was treated with 3,7-bis(diethylamino)phenoxazin-5-ium acetate by dermal application.

This study is supported by Keplingeret al(Toxicology and Applied Pharmacology; Volume 27, Issue 3, March 1974, Pages 494-506), for the closely related read across substance Disodium 4,4'-bis[(4-anilino-6-morpholino-1,3,5-triazin-2-yl)amino]stilbene-2,2'-disulphonate (16090-02-1).Acute Dermal toxicity study was conducted in rabbits at the concentration of 5000 and 10000 mg/kg bw. Test material was applied to both intact and abraded sites on rabbits. After occlusion for 24 hr, unabsorbed test material was removed and treated sites were examined for local reactions. After an observation period of 14 days, the animals were sacrificed and examined for gross pathologic changes. No Mortality observed at 10000 mg/kg bw. Moderate erythema disappearing by day 4, was observed; but there were no signs of systemic toxicity. No gross pathologic changes were observed. Therefore, LD50 was considered to be >10000 mg/kg bw, when albino rabbits were treated with Disodium 4,4'-bis[(4-anilino-6-morpholino-1,3,5-triazin-2-yl)amino]stilbene-2,2'-disulphonate occlusively for 24 h exposure by dermal application to intact and abraded sites.

The above study is further supported by Keplinger et al (Toxicology and Applied Pharmacology; Volume 27, Issue 3, March 1974, Pages 494-506), for the closely related read across substance Disodium 4,4'-bis[(4-anilino-6-morpholino-1,3,5-triazin-2-yl)amino]stilbene-2,2'-disulphonate (16090-02-1).Acute Dermal toxicity study was conducted in rabbits at the concentration of 5000 mg/kg bw. Test material was applied in the form of paste in polyethylene glycol to both intact and abraded sites on rabbits.After occlusion for 24 hr, unabsorbed test material was removed and treated sites were examined for local reactions. After an observation period of 14 days, the animals were sacrificed and examined for gross pathologic changes.No Mortality observed at 5000 mg/kg bw.Moderate erythema disappearing by day 4, was observed; but there were no signs of systemic toxicity.No gross pathologic changes were observed. Therefore, LD50 was considered to be >5000 mg/kg bw, when albino rabbits were treated with Disodium 4,4'-bis[(4-anilino-6-morpholino-1,3,5-triazin-2-yl)amino]stilbene-2,2'-disulphonate occlusively for 24 h exposure by dermal application to intact and abraded sites.

These results are further supported by U.S. National Library of Medicine (ChemIDplus, 2017), for the closely related read across substance Disodium 4,4'-bis[[6-anilino-4-[(2-hydroxyethyl)methylamino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate (13863-31-5).TheAcute Dermal toxicity study was conducted in rabbits at the concentration of 2000 mg/kg bw. No Mortality observed at 2000 mg/kg bw. Therefore, LD50 was considered to be >2000 mg/kg bw, when rabbits were treated with Disodium 4,4'-bis[[6-anilino-4-[(2-hydroxyethyl)methylamino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate by dermal application.

Thus, based on the above studies on 3,7-bis(diethylamino)phenoxazin-5-ium acetate (79916-07-7) and it’s read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 3,7-bis(diethylamino)phenoxazin-5-ium acetate can be classified as category V of acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on 3,7-bis(diethylamino)phenoxazin-5-ium acetate (79916-07-7) and it’s read across substances, it can be concluded that LD50 value is between 300 - 2000 mg/kg bw for acute oral toxicity, LD50 value is greater than 2000 mg/kg bw for acute dermal toxicity and LC50 value is greater than 5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, 3,7-bis(diethylamino)phenoxazin-5-ium acetate can be classified as category IV for acute oral, category V for acute dermal and inhalation toxicity.