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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data from peer reviewed journal

Data source

Reference
Reference Type:
publication
Title:
Chronic Toxicity, Teratologic, and Reproduction Studies with Hair Dyes
Author:
THEODORE WBRNICK et.al
Year:
1975
Bibliographic source:
TOXICOLOGY AND APPLIED PHARMACOLOGY ,1975

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Developmental toxicity study of test material was performed on rabbits.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-amino-4-nitrophenol
- Molecular Formula: C6H6N2O3
- Molecular Weight: 154.125 g/mol
- SMILES Notation: C1=CC(=C(C=C1[N+](=O)[O-])N)O
- InChI: 1S/C6H6N2O3/c7-5-3-4(8(10)11)1-2-6(5)9/h1-3,9H,7H2
- Substance type: Organic
- Physical state: solid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
No data available

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
other: 0.5 % aqueous methylcellulose
Details on exposure:
Details on exposure

PREPARATION OF DOSING SOLUTIONS:test material dissolved in 0.5 % aqueous methylcellulose

DIET PREPARATION
- Rate of preparation of diet (frequency):No data available
- Mixing appropriate amounts with (Type of food):No data available
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): 0.5 % aqueous methylcellulose
- Concentration in vehicle:0, 19.5 and 97.5mg/kg/day)
- Amount of vehicle (if gavage):1 ml/kg.
- Lot/batch no. (if required): No data available
- Purity: No data available
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Female were artificially inseminated and day of insemination was designated day 0 of pregnancy.
Duration of treatment / exposure:
13 days (on days 6 to 18 of gestation)
Frequency of treatment:
Daily
Duration of test:
30 day
Doses / concentrations
Remarks:
0, 19.5 and 97.5mg/kg bw/day
No. of animals per sex per dose:
Total : 48
0 mg/kg bw/ day: 12 female
19.5 mg/kg bw/ day: 12 female
97.5 mg/kg bw/ day: 12 female

With omposite:
97.5 mg/kg bw/ day: 12 female
Control animals:
not specified
Details on study design:
No data available

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule:
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule:

BODY WEIGHT: Yes
- Time schedule for examinations:

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes / No / No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / No data
- Time schedule for examinations:

POST-MORTEM EXAMINATIONS: Yes / No / No data
- Sacrifice on gestation day #
- Organs examined:

OTHER:
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other:
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: No data
Statistics:
Statistical analysis were performed by using the 95 % confidence level. The methods used included square test, analysis of variance and
t test, and the Fisher exact probability test (Snedecor, 1962).
Indices:
No data available
Historical control data:
No data available

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Bluebrown colored urine were observed in all treated rabbits.
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No adverse effect on body weight gain of treated rabbits were observed as compared to control.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Maternal developmental toxicity

Number of abortions:
not specified
Pre- and post-implantation loss:
no effects observed
Total litter losses by resorption:
no effects observed
Early or late resorptions:
no effects observed
Dead fetuses:
no effects observed
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
no effects observed
Description (incidence and severity):
No adverse effect onNumber of pregnancies,
Other effects:
not specified

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
97.5 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
clinical signs
body weight and weight gain
pre and post implantation loss
total litter losses by resorption
early or late resorptions
dead fetuses
changes in number of pregnant
Remarks on result:
other: No effects on reproductive performance was observed

Maternal abnormalities

Abnormalities:
not specified
Localisation:
not specified

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
No effect on fetusesweight were observed in treated female rabbits.
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified
Reduction in number of live offspring:
not specified
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
no effects observed
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Other effects:
not specified

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
97.5 mg/kg bw/day
Based on:
test mat.
Sex:
not specified
Basis for effect level:
external malformations
skeletal malformations
visceral malformations
Remarks on result:
other: no developmental toxicity was observed

Fetal abnormalities

Abnormalities:
not specified
Localisation:
other: not specified

Overall developmental toxicity

Developmental effects observed:
not specified
Treatment related:
not specified
Relation to maternal toxicity:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 97.5 mg/kg/day for F0 and F1 geneartion when New Zealand Whitefemale rabbits were treated with test material orally.
Executive summary:

In a Teratology study,New Zealand White female rabbits were treated with test material in the concentration of 0, 19.5 and 97.5 mg/kg/day orally by gavage fromday 6 to day 18 of gestation. Bluebrown colored urine were observed in all treated rabbits.

No adverse effect onbody weight gain, Number of pregnancies, numbers of corpora lutea, implantations, resorptions, and live and stillborn fetuses were observed in treated female rabbits. No effect on fetusesweight were observed in treated female rabbits. In addition, No gross abnormalities, visceral and skeletal abnormalities were observed in fetusesoftreated female rabbits. Therefore, NOAEL was considered to be 97.5 mg/kg/day for F0 and F1 geneartion when New Zealand White female rabbits were treated with test material orally by gavage for 13 days.