Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Remarks:
28 d repeated dose study
Type of information:
experimental study
Adequacy of study:
supporting 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 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 28 days to asses its toxicity. At the end of the treatment period all animals were killed and necropsied. The pathologic evaluation consisted of organ weight, gross and microscopic examination of reproductive organs, incl. testes, epididymis, prostate gland, seminal vesicle, vagina, cervix, uterus, ovary/oviduct.
GLP compliance:
yes
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity: 95.8 %
Specific details on test material used for the study:
Code Number/Test Item Gelbpigment E4GN CAS No. 68511-62-6 Molecular Formula C8H4N6O6Ni and C3H6N6 Molecular Mass (g/mol) C8H4N6O6Ni: 338.9; and C3H6N6: 126.1 CAS-Name, Chemical Name: Nickel, 5,5'-azobis-2,4,6(1 H,3H,5H)-pyrimidinetrione Purity 95.8% Appearance Yellow solid Storage Room temperature

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)
Duration of treatment / exposure:
28 days
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

Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No histopathological changes were found in testes, epididymis, prostate gland, seminal vesicle, vagina, cervix, uterus, ovary/oviduct

Observed effects

No histopathological changes were found in testes, epididymis, prostate gland, seminal vesicle, vagina, cervix, uterus, ovary/oviduct

Any other information on results incl. tables

There were no test substance-related toxic changes in organs weights of testes, epididymis, prostate gland, seminal vesicle, vagina, cervix, uterus, ovary/oviduct. No histopathological changes were found in testes, epididymis, prostate gland, seminal vesicle, vagina, cervix, uterus, ovary/oviduct and all other examined organs.

Applicant's summary and conclusion

Executive summary:

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 28 days to asses its toxicity. At the end of the treatment period all animals were killed and necropsied. The pathologic evaluation consisted of organ weight, gross and microscopic examination of reproductive organs, incl. testes, epididymis, prostate gland, seminal vesicle, vagina, cervix, uterus, ovary/oviduct.

No evidence of toxicity to reproduction was observed in a subacute repeated dose study as no treatment-related changes were observed for any reproductive organ investigated during macroscopic and microscopic examination. On the basis of this study no effects on fertility were expected (NOAEL, rat: 1000 mg/kg bw/day).