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Toxicological information

Repeated dose toxicity: oral

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test Item: Gelbpigment E4GN

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

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
Doses / concentrations
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

Results and discussion

Effect levels

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

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.