Registration Dossier

Administrative data

Endpoint:
one-generation reproductive toxicity
Remarks:
based on generations indicated in Effect levels (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from peer reviewed journal

Data source

Reference
Reference Type:
publication
Title:
Final Report on the Safety Assessment of Basic Blue 991
Author:
American College of Toxicology
Year:
2007
Bibliographic source:
International Journal of Toxicology, 26(Suppl. 2):51–63, 2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
The reporductive effects of basic blue 99 were evaluated on sprague dawley CD rats on the 6th to the 15th gestation days
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):Basic blue 99- Molecular formula (if other than submission substance): C19-H20-Br-N4-O2.Cl- Molecular weight (if other than submission substance): 451.75 g/mol- Substance type:Organic- Physical state:Solid- Impurities (identity and concentrations):-Purity-63%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
No data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on mating procedure:
- M/F ratio per cage:No data- Length of cohabitation:- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancyNo data- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.No data- Further matings after two unsuccessful attempts: [no / yes (explain)]No data- After successful mating each pregnant female was caged (how):No data- Any other deviations from standard protocol:Analytical verification of dosesYes/NoNo dataDetails on analytical verification of dosesNo data
Duration of treatment / exposure:
20 days
Frequency of treatment:
Doses were given on 6th to the 15th gestation days.
Details on study schedule:
No data
Doses / concentrations
Remarks:
Doses / Concentrations:50 mg/ kg/dayBasis:nominal in water
No. of animals per sex per dose:
29 pregnant females
Control animals:
yes, concurrent no treatment
Details on study design:
No data
Positive control:
No data

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: No DETAILED CLINICAL OBSERVATIONS: NoBODY WEIGHT: Yes
Oestrous cyclicity (parental animals):
No details
Litter observations:
weight of the placenta, uterus, fetuses, dams, body weight gain, and sex of the fetuses were recorded.
Postmortem examinations (parental animals):
On day 20 the rats were killed and cesarean sections were performed.
Postmortem examinations (offspring):
HISTOPATHOLOGY / ORGAN WEIGTHS:Yes
Reproductive indices:
The number of implantation sites, resorptions, living fetuses, and the number of corpora lutea were counted in each dam. The weight of the placenta, uterus, fetuses, dams, body weight gain, and sex of the fetuses were recorded.
Offspring viability indices:
No dams died

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Test animals had no differences in mean body weight gain in the course of gestation as compared to controls.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Test animals had no differences in mean body weight gain in the course of gestation as compared to controls.
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
organ weights and organ / body weight ratios
reproductive function (oestrous cycle)

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Yes. The weight of the placenta, uterus, fetuses, dams, body weight gain, and sex of the fetuses were recorded.
Gross pathological findings:
not specified
Histopathological findings:
not specified

Details on results (F1)

No dams died or showed cumulative toxicity effect from the applied dose of 50 mg/kg Basic Blue 99.One-third of the litter was examined for soft tissue anomalies and the remaining fetuses were examined for skeletal anomalies.

Effect levels (F1)

Dose descriptor:
NOEL
Generation:
F1
Effect level:
50 mg/kg bw/day
Based on:
test mat.
Sex:
female
Remarks on result:
other: The organ weights of dams and theeffects on the body weights.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
There were no treatment related effects. Based on the effects it is concluded that Basic Blue 99 at 50 mg/kg did not cause embryotoxic or teratogenic effects under the test conditions
Executive summary:

The reporductive effects of basic blue 99 were evaluated on sprague dawley CD rats on the 6th to the 15th gestation days.50mg/kg.Controls animals were dosed with distilled water vehicle. The parameters checked includeimplantation sites, resorptions, living fetuses, and the number of corpora lutea.The weight of the placenta, uterus, fetuses, dams, body weight gain, and sex of the fetuses were recorded.Test animals had no differences in mean body weight gain in the course of gestation as compared to controls.There were no treatment related effects and 50mg/kg can be concluded as NOEL.