5-[[p-(benzylmethylamino)phenyl]azo]-1,4-dimethyl-1H-1,2,4-triazolium chloride

Developmental toxicity / teratogenicity

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 on: Basic Red 51 (COLIPA n° B116)

Author:

European Commission (EC) - Scientific Committee on Consumer Safety (SCCS)

Year:

2010

Bibliographic source:

Basic Red 51 (COLIPA n° B116) SCCS/1332/10

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Principles of method if other than guideline:

Teratogenicity study of Basic Red 51 was performed on wistar rats via oral gavage for Days 6 to 17 post coitum.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-[[4-(dimethylamino)phenyl]azo]-1,3-dimethyl-1H-imidazolium chloride

EC Number:

278-601-4

EC Name:

2-[[4-(dimethylamino)phenyl]azo]-1,3-dimethyl-1H-imidazolium chloride

Cas Number:

77061-58-6

Molecular formula:

C13H18N5.Cl

IUPAC Name:

2-[[4-(Dimethylamino)phenyl]azo]-1,3-dimethyl-1H-imidazolium chloride

Details on test material:

- Name of test material (IUPAC name): 2-[[4-(Dimethylamino)phenyl]azo]-1,3-dimethyl-1H-imidazolium chloride
- Common name: Basic Red 51
- Molecular formula: C13H18N5.Cl
- Molecular weight: 279.773 g/mol
- Smiles notation: c1([n+](ccn1C)C)\N=N\c1ccc(cc1)N(C)C.[ClH-]
- InChl: 1S/C13H18N5.ClH/c1-16(2)12-7-5-11(6-8-12)14-15-13-17(3)9-10-18(13)4;/h5-10H,1-4H3;1H/q+1;/p-1
- Substance type: Organic

Specific details on test material used for the study:

- Name of test material (IUPAC name): 2-[[4-(Dimethylamino)phenyl]azo]-1,3-dimethyl-1H-imidazolium chloride
- Common name: Basic Red 51
- Molecular formula: C13H18N5.Cl
- Molecular weight: 279.773 g/mol
- Smiles notation: c1([n+](ccn1C)C)\N=N\c1ccc(cc1)N(C)C.[ClH-]
- InChl: 1S/C13H18N5.ClH/c1-16(2)12-7-5-11(6-8-12)14-15-13-17(3)9-10-18(13)4;/h5-10H,1-4H3;1H/q+1;/p-1
- Substance type: Organic

Test animals

Species:

rat

Strain:

Wistar

Remarks:

(Hanlbm (SPF))

Details on test animals or test system and environmental conditions:

No data available

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Double distilled water

Details on exposure:

Details on exposure
PREPARATION OF DOSING SOLUTIONS:
The test material diluted with Double distilled water
DIET PREPARATION
- Rate of preparation of diet (frequency):
- 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: 0, 20, 60 and 180 mg/kg bw/day
- Amount of vehicle (if gavage): 10ml/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:

Mated female used

Duration of treatment / exposure:

11 days (Days 6 to 17 post coitum)

Frequency of treatment:

once a daily

Duration of test:

No data available

Doses / concentrations

Remarks:

0, 20, 60 and 180 mg/kg bw/day

No. of animals per sex per dose:

Total:240
0 mg/kg bw:22 female
20 mg/kg bw:22 female
60 mg/kg bw:22 female
180 mg/kg bw:22 female

Control animals:

yes, concurrent vehicle

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: Clinical observations and mortality were recorded at least twice daily.


BODY WEIGHT: Yes
Time schedule for examinations: body weight was recorded daily from day 0 until day 21 post coitum.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes Food consumption was recorded for the following periods: days 0-6, 6-12, 12-18 and 18-21 post coitum;

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: Yes
- Number of implantations: Yes
- Number of early resorptions: No data
- Number of late resorptions: No data
- Other:The uteri of all females with live foetuses were weighed at necropsy on day 21 post coitum;

Fetal examinations:

- External examinations: Yes
- Soft tissue examinations: No data
- Skeletal examinations: Yes
- Head examinations: No data

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:

no effects observed

Description (incidence and severity):

Clinical signs of toxicity or reactions to treatment did not occur in any group.

Dermal irritation (if dermal study):

not specified

Mortality:

no mortality observed

Description (incidence):

Maternal deaths did not occur during the study

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

The mean body weight gain was reduced only in the 180 mg/kg bw/day dose group, these data being correlated with the decreased food consumption

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

A dose-dependent reduction of the food consumption was observed during the treatment period in the 60 and 180 mg/kg bw/day dose groups (-7.6% and -23.5% respectively); an increase of + 5.5 % was observed in the 180 mg/kg bw/day dose group after the treatment period.

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

Description (incidence and severity):

Mean post-implantation loss was similar between treated and control dams in the 60 and 180 mg/kg bw/day dose groups.The increased post-implantation loss observed only in the 60 mg/kg bw/day dose group was considered to be incidental. No abnormal findings were noted in any female of any treated 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:

no effects observed

Description (incidence and severity):

The mean number of foetuses per dam was similar between treated and control dams in the 60 and 180 mg/kg bw/day dose groups.

Effect levels (maternal animals)

Dose descriptor:

NOEL

Effect level:

20 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

body weight and weight gain

clinical signs

food consumption and compound intake

mortality

pre and post implantation loss

Remarks on result:

other: No treatment related effets was observed

Maternal abnormalities

Abnormalities:

not specified

Results (fetuses)

Fetal body weight changes:

no effects observed

Description (incidence and severity):

The mean foetal body weights were similar in all groups except for a slight increase observed in the 60 mg/kg bw/day dose group, which was attributed to the slightly reduced mean number of foetuses per dam.

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:

no effects observed

Description (incidence and severity):

The sex ratio for foetuses was similar in all groups

Changes in litter size and weights:

not specified

Changes in postnatal survival:

not specified

External malformations:

not specified

Skeletal malformations:

no effects observed

Description (incidence and severity):

Some abnormal findings were noted during foetal examination: externally, one cleft palate was observed in the 20 mg/kg bw/day dose group. Skeletal changes included a small number of foetuses in each group with abnormally shaped sternebrae. These were not considered related to the test substance, as they were within the range for historical controls.

Visceral malformations:

not specified

Other effects:

not specified

Effect levels (fetuses)

Dose descriptor:

NOEL

Effect level:

180 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

changes in sex ratio

fetal/pup body weight changes

skeletal malformations

Remarks on result:

other: No overall developmental effects was observed

Fetal abnormalities

Abnormalities:

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:

In developmental toxicity study, the NOEL was considered to be for the maternal effects is 20 mg/kg bw/day and for foetal effects the NOEL is 180 mg/kg bw/day ,The test material did not affects reproductive parameter and not toxic to embryo or foetus. When mated female wistar rats treated with Basic Red 51 (77061-58-6) via oral gavage for Days 6 to 17 post coitum

Executive summary:

The developmental toxicity study of Basic Red 51 (77061-58-6) was performed on mated female  wistar (Hanlbm (SPF) rats according to OECD 414.22 mated female per dose group were administered with 10ml /kg aqueous solution of test material in dose concentration0, 20, 60 and 180 mg/kg bw/dayonce daily for 11 days (Days 6 to 17 post coitum).While The control group received only the vehicle (double distilled water).Food consumption was recorded for the following periods: days 0-6, 6-12, 12-18 and 18-21 post coitum; body weight was recorded daily from day 0 until day 21 post coitum. Clinical observations and mortality were recorded at least twice daily. At post mortem, on day 21, necropsy, all internal organs were examined with emphasis on the uterus, uterine contents, position of foetuses in the uterus and number of corpora lutea. The uteri of all females with live foetuses were weighed at necropsy on day 21 post coitum; the foetuses were removed from the uterus, weighed, sexed, and examined for gross external abnormalities.

 

Maternal deaths did not occur during the study and clinical signs of toxicity or reactions to treatment did not occur in any group. A dose-dependent reduction of the food consumption was observed during the treatment period in the mid- and high-dose groups (-7.6% and - 23.5% respectively); an increase of + 5.5 % was observed in the high dose group after the treatment period. The mean body weight gain was reduced only in the high dose group, these data being correlated with the decreased food consumption. Mean post-implantation loss and mean number of foetuses per dam were similar between treated and control dams in the low- and mid-dose groups. The increased post-implantation loss observed only in the mid dose group was considered to be incidental. No abnormal findings were noted in any female of any treated group. The mean foetal body weights were similar in all groups except for a slight increase observed in the mid-dose group, which was attributed to the slightly reduced mean number of foetuses per dam. The sex ratio for foetuses was similar in all groups. Some abnormal findings were noted during foetal examination: externally, one cleft palate was observed in the low dose group. Skeletal changes included a small number of foetuses in each group with abnormally shaped sternebrae. These were not considered related to the test substance, as they were within the range for historical controls. Hencethe NOEL was considered to befor the maternal effects is 20 mg/kg bw/day and for foetal effects the NOEL is 180 mg/kg bw/day ,The test material did not affects reproductive parameter and not toxic to embryo or foetus.When mated female wistar rats treated with Basic Red 51 (77061-58-6)via oral gavage for Days 6 to 17 post coitum