Registration Dossier

Administrative data

Description of key information

Most azo dyes have acute oral and dermal toxicity discriminating dose > 2000 mg/kg. The similar substances and the test substance reviewed fall into this category.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2016
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Based on reliable review of literature and assessment of similar sulphonated azo dyes. No further animal testing is justified.
Justification for type of information:
Assessment based on structural activity and grouping with similar substances
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Various methods are reporting, but most data is from historical LD50 work although the discriminating dose has been possible to determine.
GLP compliance:
not specified
Test type:
other: Review of various methods
Limit test:
no
Species:
rat
Sex:
male/female
Route of administration:
oral: gavage
Doses:
Dose levels up to 5000 mg/kg are reported for some substances
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
> 2 000 mg/kg bw
Based on:
other: estimation
Mortality:
No mortality noted in any of the substances reviewed at dose levels up to 2000 mg/kg
Clinical signs:
Other than post-dosing distress (excessive grooming, subdued behaviour etc) the main clinical sign has been discolouration of the animals
This may in part be due to urine or feaces, but longer term studies confirm absorption and discolouration of skin not due to grooming.
Body weight:
No effects noted
Gross pathology:
Discolouration noted. Liver effects reports in some cases, but these may be adaptive.
Other findings:
Discolouration
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Review of similar substances and publications relating to azo dyes, concluded low oral toxicity
No further animal testing can be justified.
Executive summary:

From various data sources, it is considered unlikely that the substance will be acutely toxic. Most azo dyes have acute toxicity discriminating dose > 2000 mg/kg and the similar substances reviewed fall into this category.

 

The impact of lithium is not likely to impact on the toxicity as the w/w content of lithium is not significant in the classification.

 

There is evidence that the substance is absorbed by ingestion and there are many publications relating to possible metabolic processes [ref ]. Discolouration of whole animals is regularly reported suggesting absorption and distribution.

 

Although not full assessed for this low-volume registration, longer term studies have also been reviewed and adverse effects (mainly liver and kidneys) are seen in many azo dyes. However, none of the specific substances reviewed are classified as STOT RE as the adverse effect levels are above threshold for classification. There is also some debate as to whether the liver changes are adaptive and recovery will occur or whether these are ‘adverse’.

 

It is not considered justifiable to perform further acute oral toxicity testing on CJ313 in view of the similarity with other dyes assessed in this report

Ref: Azo Dyes and Their Metabolites,Farah Maria Drumond Chequer et al, Intechopen.com

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Reliable assessment based on similar substances.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Limited exposure evisaged.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2016
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Based on reliable review of literature and assessment of similar sulphonated azo dyes. No further animal testing is justified.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Methods not always explicit in reviews, but OECD testing principles appear to have been followed in most cases.
GLP compliance:
not specified
Test type:
other: Review of various studies
Limit test:
no
Species:
rat
Sex:
male/female
Details on test animals and environmental conditions:
Mostly rat data, but dermal effects on guinea pigs and rabbits also examined (non-maximised sensitisation studies and dermal irritation)
Type of coverage:
not specified
Vehicle:
not specified
Doses:
Up to 2000 mg/kg
Control animals:
not specified
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality reported
Clinical signs:
Other than discolouration, no clinical signs
Gross pathology:
No adverse systemic effects reported.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on reliable review of literature and assessment of similar sulphonated azo dyes.
No further animal testing is justified.
Executive summary:

From assessment of similar sulphonated azo dyes, none are noted as being acutely toxic and there is no evidence of dermal absorption. From various data sources, it is considered unlikely that the substance will be acutely toxic by the dermal route. Most azo dyes have acute toxicity discriminating dose > 2000 mg/kg and the similar substances reviewed fall into this category.

 

The impact of lithium is not likely to impact on the toxicity when comparing with sodium salts as dermal toxicity of lithium substances are reported to be low and in view of the minimal % w/w content of lithium, this is not significant in the classification of toxicity.

 

Studies on guinea pigs and rabbits for sensitising and irritancy assessment have not revealed any evidence of adverse systemic effects. Only the maximised sensitising studies (ie injected) appear to give positive results, confirming low levels of dermal absorption. Discolouration of skin will occur and the colour is difficult to wash off.

 

It is not considered justifiable to perform further acute dermal toxicity testing on CJ313 in view of the similarity with other dyes assessed in this report. It should also be noted that some other registrations have indicated waivers for this endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
This class of substance considered to be of low toxicity and not likely to be absorbed dermally.

Additional information

Acute oral toxicity

From various data sources, it is considered unlikely that the substance will be acutely toxic. Most azo dyes have acute toxicity discriminating dose > 2000 mg/kg and the similar substances reviewed fall into this category.

 

The impact of lithium is not likely to impact on the toxicity as the w/w content of lithium is not significant in the classification.

 

There is evidence that the substance is absorbed by ingestion and there are many publications relating to possible metabolic processes [ref ]. Discolouration of whole animals is regularly reported suggesting absorption and distribution.

 

Although not full assessed for this low-volume registration, longer term studies have also been reviewed and adverse effects (mainly liver and kidneys) are seen in many azo dyes. However, none of the specific substances reviewed are classified as STOT RE as the adverse effect levels are above threshold for classification. There is also some debate as to whether the liver changes are adaptive and recovery will occur or whether these are ‘adverse’.

 

It is not considered justifiable to perform further acute oral toxicity testing on CJ313 in view of the similarity with other dyes assessed in this report

Ref: Azo Dyes and Their Metabolites,Farah Maria Drumond Chequer et al, Intechopen.com

Acute dermal toxicity

From assessment of similar sulphonated azo dyes, none are noted as being acutely toxic and there is no evidence of dermal absorption. From various data sources, it is considered unlikely that the substance will be acutely toxic by the dermal route. Most azo dyes have acute toxicity discriminating dose > 2000 mg/kg and the similar substances reviewed fall into this category.

 

The impact of lithium is not likely to impact on the toxicity when comparing with sodium salts as dermal toxicity of lithium substances are reported to be low and in view of the minimal % w/w content of lithium, this is not significant in the classification of toxicity.

 

Studies on guinea pigs and rabbits for sensitising and irritancy assessment have not revealed any evidence of adverse systemic effects. Only the maximised sensitising studies (ie injected) appear to give positive results, confirming low levels of dermal absorption. Discolouration of skin will occur and the colour is difficult to wash off.

 

It is not considered justifiable to perform further acute dermal toxicity testing on CJ313 in view of the similarity with other dyes assessed in this report. It should also be noted that some other registrations have indicated waivers for this endpoint.

Justification for selection of acute toxicity – oral endpoint

Based on reliable review of literature and assessment of similar sulphonated azo dyes.

No further animal testing is justified.

Justification for selection of acute toxicity – dermal endpoint

Based on reliable review of literature and assessment of similar sulphonated azo dyes.

No further animal testing is justified.

Justification for classification or non-classification

According to the available data, the test substance is not classified.