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Diss Factsheets

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:
equivalent or similar to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Developmental toxicity study of test material was performed on rats .
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-amino-4-nitrophenol
EC Number:
202-767-9
EC Name:
2-amino-4-nitrophenol
Cas Number:
99-57-0
Molecular formula:
C6H6N2O3
IUPAC Name:
2-amino-4-nitrophenol
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:
rat
Strain:
other: CFE-S
Details on test animals or test system and environmental conditions:
Details on test animal & Environmental conditions

TEST ANIMALS
- Source:Carworth Farms,Inc.,New City,New York.
- Age at study initiation: No data available
- Weight at study initiation:15-wk-old
- Fasting period before study:No data available
- Housing:Pregnant female rats were housed in individual cages.
- Diet (e.g. ad libitum):No data available
- Water (e.g. ad libitum):No data available
- Acclimation period: No data available

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Details on exposure:
Details on exposure

PREPARATION OF DOSING SOLUTIONS:test material was mixed into the basal diet at concentrations of 0, 1950 and 7800 ppm.

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):No data available
- Concentration in vehicle:0,1950 and 7800 ppm(0, 195 and 616 mg/kg bw/day)
- Amount of vehicle (if gavage):No data available
- Lot/batch no. (if required): No data available
- Purity: No data available
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Details of mating
- M/F ratio per cage: 1 : 1 ratio
- Length of cohabitation: No data available
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy:Sperm in vaginal smear referred to as day 0 of pregnancy
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.No data available
- Further matings after two unsuccessful attempts: [no / yes (explain)]No data available
- After successful mating each pregnant female was caged (how):Individually
- Any other deviations from standard protocol:Pregnancy was further confirmed by biweekly weighing of the females.
Duration of treatment / exposure:
10 days (Day 6 to day 15 of gestation)
Frequency of treatment:
Daily
Duration of test:
20 days
Doses / concentrations
Remarks:
0, 195 and 616 mg/kg bw/day
No. of animals per sex per dose:
Total : 60
0 mg/kg bw/ day: 20 female
195 mg/kg bw/ day: 20 female
616 mg/kg bw/ day: 20 female
Control animals:
yes

Examinations

Maternal examinations:
Clincal sign were observed.
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 rats.
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
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:
no effects observed
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:
not specified
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:
not specified
Other effects:
not specified
Details on maternal toxic effects:
No adverse effect onaverage number of implantation sites, live pups or in the number of females with one or more resorption sites were observed in treated female rats.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
616 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
clinical signs
early or late resorptions
pre and post implantation loss
total litter losses by resorption
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 rats.
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:
616 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
fetal/pup body weight changes
external malformations
skeletal malformations
visceral malformations
Remarks on result:
other: No developmental toxic effects were 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 616mg/kg/day for F0 and F1 geneartion when CFE-S female rats were treated with test material orally.
Executive summary:

In a Teratology study,CFE-S female rats were treated with test material in the concentration of 0, 195 and 616 mg/kg/day orally in diet fromday 6 to day 15 of gestation. No adverse effect onaverage number of implantation sites, live pups or in the number of females with one or more resorption sites were observed in treated female rats. No effect on fetuses weight were observed in treated female rats. In addition, No were gross abnormalities, visceral and skeletal abnormalities were observed in fetusesoftreated female rats. Therefore, NOAEL was considered to be 616mg/kg/day for F0 and F1 geneartion when CFE-S female rats were treated with test material orally in diet for 10 days.