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

Toxicity to reproduction: other studies

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

Test material information

Constituent 1

Reference substance name:

Gelbpigment E4GN

IUPAC Name:

Gelbpigment E4GN

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).