Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data from secondary source

Data source

Reference
Reference Type:
secondary source
Title:
Opinion of the Scientific Committee on Consumer Safety on Basic Violet 2 (B115)
Author:
Scientific Committee ON Consumer Products – SCCP
Year:
2011
Bibliographic source:
Scientific Committee ON Consumer Products – SCCP , COLIPA no B115 during 12th plenary meeting of 20 September 2011

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
Prenatal developmental toxicity study 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloridewas performed on Sprague Dawley rats.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Basic Violet 2
- IUPAC name: 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride
- Molecular formula: C22H23N3ClH
- Molecular weight: 365.906 g/mol
- Substance type: Organic
- Physical state: No data
Specific details on test material used for the study:
- Name of test material: Basic Violet 2
- IUPAC name: 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride
- Molecular formula: C22H23N3ClH
- Molecular weight: 365.906 g/mol
- Substance type: Organic
- Physical state: No data
- Purity:No data
- Impurities (identity and concentrations): No data

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Hsd: SD strain
Details on test animals and environmental conditions:
No data available

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
water
Remarks:
Distilled water
Details on exposure:
Details on exposure
PREPARATION OF DOSING SOLUTIONS:
Test material dissolved in distilled water
DIET PREPARATION
- Rate of preparation of diet (frequency):No data available
- Mixing appropriate amounts with (Type of food )
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle: 2,10 and 50 mg/kg bw/day
- Amount of vehicle (if gavage): 10ml/kg bw/day

- Lot/batch no. (if required): No data available
- Purity: No data available
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
No data available
Duration of treatment / exposure:
9 days ( from day 6 through day 15 gestation)
Frequency of treatment:
Daily
Duration of test:
9 days ( from day 6 through day 15 gestation)
Doses / concentrations
Remarks:
2,10 and 50 mg/kg bw/day
No. of animals per sex per dose:
Total:72
2mg/kg bw/day:24
10mg/kg bw/day:24
50 mg/kg bw/day:24
Control animals:
not specified
Details on study design:
No data available

Examinations

Maternal examinations:
Parental animals observation and examinations
CAGE SIDE OBSERVATIONS: yes

DETAILED CLINICAL OBSERVATIONS: Yes

Time schedule:


BODY WEIGHT: Yes
Time schedule for examinations:
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes Food consumption was determined weekly.

Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data available


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

OTHER:
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: No data
- Number of implantations: Yes
- Number of early resorptions: No data
- Number of late resorptions: No data
- Other:
Fetal examinations:
- External examinations: Yes:
- Soft tissue examinations: Yes:
- Skeletal examinations: Yes:
- Head examinations: Yes:
Statistics:
No data available
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):
Violet coloured faeces in 10mg/kg bw/day and 50mg/kg bw/day dose groups while Dyspnoea in 50mg/kg bw/day group were observed.
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
body weight reduced in 50mg/kg bw/day group from day 8
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Reduction in food consumption was observed during treatment
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:
effects observed, treatment-related
Description (incidence and severity):
At necropsy final body weight, uterus weight and corrected body weight were decreased in 50mg/kg bw/day dose group
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
Description (incidence and severity):
The number of implantations was decreased in 50mg/kg bw/day dose group.
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
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

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
10 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
clinical signs
body weight and weight gain
food consumption and compound intake
gross pathology
pre and post implantation loss
Remarks on result:
other: No effect observed in given dose
Dose descriptor:
LOAEL
Effect level:
50 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
body weight and weight gain
organ weights and organ / body weight ratios
other: The number of implantations was decreased in 50mg/kg bw/day dose group.
Remarks on result:
other: Adverse effects was observed at given dose level

Maternal abnormalities

Abnormalities:
not specified

Results (fetuses)

Fetal body weight changes:
effects observed, treatment-related
Description (incidence and severity):
Foetal weight was decreased in the 50mg/kg bw/day dose group
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
Description (incidence and severity):
no treatment related effects was observed in any dose group.
Skeletal malformations:
no effects observed
Description (incidence and severity):
no treatment related effects was observed in any dose group.
Visceral malformations:
no effects observed
Description (incidence and severity):
no treatment related effects was observed in any dose group.
Other effects:
not specified

Effect levels (fetuses)

open allclose all
Dose descriptor:
NOAEL
Effect level:
10 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 effect was observed
Dose descriptor:
LOAEL
Effect level:
50 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
fetal/pup body weight changes
Remarks on result:
other: Decrease in body weight was observed at given dose level

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
no
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:
No Observed Adverse Effect Level (NOAEL) was considered to be 10mg/kg/day and LOAEL was considered to be 50 mg/kg bw .When female Sprague Dawley rats were treated with 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7) orally.
Executive summary:

Prenatal development toxicity study of  with4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7)was performed on female Sprague Dawley  Hsd: SD strainrats. 72 rats were divided as 24 rats /dose group. The test materialdissolved in water were administers in dose concentration 0, 5, 10and 50 mg/kg bw/day from day 6 through day 15of gestationby oral gavage route. Animals were observed for clinical signs, Food consumption and body weight .On day 20 post-coitum, the dams were sacrificed and subjected to a macroscopic examination. The litter parameters like number of implantation sites. The foetuses were weighed and subjected to external, soft tissue or skeletal examinations.Clinical sings like violet coloured faeces in 10mg/kg bw/day and 50mg/kg bw/day dose groups while dyspnoea in 50mg/kg bw/day group were observed.Body weightreduced in 50mg/kg bw/day group from day 8 and reductionin food consumptionwas observed during treatment. At necropsy final body weight, uterus weight and corrected body weight were decreased in 50mg/kg bw/day dose group in dams were noted. In litter the number of implantations was decreased in 50mg/kg bw/day dose group and foetal weight decrease in 50mg/kg bw/day dose group but no treatment related effects were observed in Foetal visceral and skeletal examination at any dose group. Hence No Observed Adverse Effect Level (NOAEL) was considered to be 10mg/kg/day and LOAEL was considered to be 50mg/kg bw.When female Sprague Dawley rats were treated with 4,4'-[(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methylene]bis(2-methylaniline) hydrochloride(3248-91-7) orally.