Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Gelbpigment E4GN was administered by gavage to 5 male and 5 female Wistar rats per dose group in daily doses of 0, 100, 300 or 1000 mg/kg body weight for 29 days. 
The animals were regularly observed and weighed and food and water intakes were determined. In addition, clinical pathology of blood samples was performed. Organs and tissues were subjected to gross and histopathological investigation. Functional observational battery (FOB) and motor and locomotor activity measurements (MA/LMA) were done.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Principles of method if other than guideline:
Gelbpigment E4GN was administered orally by gavage to 5 male and 5 female Wistar (HsdRCCHan:Wist) rats per dose group using ethanol/ Kolliphor HS15/ tap water (10%/ 40%/ 50%; v/v/v) as vehicle, in daily doses of 0, 100, 300, 1000 mg/kg b.w. for a period of 4 weeks. The animals were regularly observed and weighed and food and water intakes were determined. In addition, clinical laboratory investigation of blood samples was performed. Organs and tissues were subjected to gross and histopathological investigation.
GLP compliance:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: ethanol/ Kolliphor HS15/ tap water (10%/ 40%/ 50%; v/v/v)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:0, 100, 300, 1000 mg/kg b.w. Basis:other: nominal
No. of animals per sex per dose:
5 male and 5 female rats/dose
Control animals:
yes, concurrent vehicle
Key result
Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: 1000 mg/kg bw was the highest applied dose
Critical effects observed:
not specified

Survival was not affected by the treatment with the test substance.

At clinical observations the only treatment-related finding was that the color of feces was changed (yellowish) in cages of treatment groups. It seems to be obvious that this finding is caused by the color of Gelbpigment E4GN.

At histopathology some yellowish material was seen in the lumen of the large intestine (cecum, colon, rectum) of almost all rats treated with 1000 mg/kg and, additionally, in the rat of the 300 mg/kg group, which died during blood sampling. However, in all cases no such material was detected intracellularly or related to any other lesion seen in the affected organs. Therefore, this is assessed to be a sign of exposure and not as adverse.

Body weight development of males and females was not retarded by the treatment up to 1000 mg/kg. Mean food and water intake in treated groups was not relevantly changed.

Neither hematology nor clinical chemistry gave evidence for toxicologically relevant treatment-related effects up to 1000 mg/kg.

Executive summary:

Gelbpigment E4GN was administered orally by gavage to 5 male and 5 female Wistar (HsdRCCHan:Wist) rats per dose group using ethanol/ Kolliphor HS15/ tap water (10%/ 40%/ 50%; v/v/v) as vehicle, in daily doses of 0, 100, 300, 1000 mg/kg b.w. for a period of 4 weeks.

Survival was not affected by the treatment with the test substance.

At clinical observations the only treatment-related finding was that the color of feces was changed (yellowish) in cages of treatment groups. It seems to be obvious that this finding is caused by the color of Gelbpigment E4GN.

At histopathology some yellowish material was seen in the lumen of the large intestine (cecum, colon, rectum) of almost all rats treated with 1000 mg/kg and, additionally, in the rat of the 300 mg/kg group, which died during blood sampling. However, in all cases no such material was detected intracellularly or related to any other lesion seen in the affected organs. Therefore, this is assessed to be a sign of exposure and not as adverse.

Body weight development of males and females was not retarded by the treatment up to 1000 mg/kg. Mean food and water intake in treated groups was not relevantly changed.

Neither hematology nor clinical chemistry gave evidence for toxicologically relevant treatment-related effects up to 1000 mg/kg.

Under the conditions described the no observed-adverse-effect level (NOAEL) for repeated oral administration of Gelbpigment E4GN to male and female Wistar rats was >1000 mg/kg b.w.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The materials/methods and results are described in detail und are sufficient for evaluation

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The no-observed-adverse-effect-level (NOAEL) for Gelbpigment E4GN is > 1000 mg/kg based (1000 mg/kg bw was the highest applied dose). The only treatment findings were the colour of faces (yellowish changed) and yellowish material at histopathology in the lumen in the large intestine (cecum, colon, rectum) of almost all rats treated with 1000 mg/kg bw. It seems obvious that this findings are caused by the colour of Gelbpigment E4GN.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
only available study

Justification for classification or non-classification

Survival was not affected by the treatment with the test substance and no functional or morphological changes were observed. Therefore a classification is not justified.