Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline stud< and GLP
Cross-reference
Reason / purpose:
reference to same study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD TG 407
GLP compliance:
yes
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid
Details on test material:
content: 80.7 %

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 6 weeks
- Weight at study initiation:
---males: 185g (174-193 g)
---females: 139 g (132-149g)

- Fasting period before study:
- Housing: in groups of 2-3 animals per cage
- Diet ad libitum
- Water ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 55
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light) 12/12:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
groups of male and female Wistar rats recieved daily doses of the test item by gavage
(males 30 days and females 31 days) ;the test item was dissolved in water; the administration volume was 10 ml/kg bw
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
anylysis for stability and homogenicity
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
daily
Duration of test:
4 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
100, 300, 1000 mg/kg bw/day
Basis:

No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Details on study design:
groups of male and female rats received daily doses of the test item which was dissolved ibn water, Treatment time for males included 30 days and for females 31 days. Animals were observed twice daily for mortality and morbidity, once daily for cliinical signs and were weighed, food and water consumption weekly
Statistics:
Dunnett-test, Dunnett exact homogenous test and heterogenous after logarithmic transformation, adjusted Mann-Whitney-U-test, Bonferroni Mann-Whitney U-test

Results and discussion

Effect levels

open allclose all
Dose descriptor:
other: NOAEL (general toxicity)
Effect level:
ca. 1 000 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: the treatment related slight discolorations are due to the staining property of the test item
Dose descriptor:
other: NOAEL (reproductive organs)
Effect level:
ca. 1 000 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: no adverse effects observed

Observed effects

For general toxicity see section 7.5.1 repeated dose toxicity: oral
For reproductive organs.
No adverse effects observed

Applicant's summary and conclusion

Executive summary:

100, 300 and 1000 mg/kg bw/day Nigrosin WLF dissolved in tap water, was administered orally by gavage to 5 male and 5 female Wistar rats per dose group for a period of 4 weeks according to OECD TG 407 and GLP in which also the effects on reproductive organs are examined.. For general toxicity see ther respective section of repeated dose toxicity. With regard to the reproductive organs no adverse effects are observed . Therefore, the NOAEL (reproductive toxicity) is considered 1000 mg/kg bw/day