Reaction mass of melamine and Nickel, 5,5'-azobis-2,4,6(1H,3H,5H)-pyrimidinetrione complexes

Repeated dose toxicity: oral

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

Test material information

Constituent 1

Reference substance name:

Gelbpigment E4GN

IUPAC Name:

Gelbpigment E4GN

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.