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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / 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:
other: OECD 414
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
Justification for study design:
No data available

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 species / strain selection:
No data available
Sex:
female
Details on test animals 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
Details on mating procedure:
Mated female used
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
11 days (Days 6 to 17 post coitum)
Frequency of treatment:
once a daily
Details on study schedule:
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
Positive control:
No data available

Examinations

Parental animals: Observations and 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:
Oestrous cyclicity (parental animals):
No data available
Sperm parameters (parental animals):
No data available
Litter observations:
No data available
Postmortem examinations (parental animals):
Postmortem examinations (Parent Animal)
SACRIFICE :on day 21,
Male animals:
Maternal animals: yes
GROSS 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;

Postmortem examinations (offspring):
SACRIFICE
- The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at [#?] days of age.
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows: The foetuses were removed from the uterus, weighed, sexed, and examined for gross external abnormalities.

GROSS NECROPSY
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]

HISTOPATHOLOGY / ORGAN WEIGTHS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.
Statistics:
No data available
Reproductive indices:
No data available
Offspring viability indices:
No data available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

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
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: 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:
no effects observed
Description (incidence and severity):
Mean post-implantation loss and mean number of foetuses per dam 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.

Effect levels (P0)

Dose descriptor:
NOEL
Effect level:
20 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
body weight and weight gain
food consumption and compound intake
Remarks on result:
other: No effects observed at given dose level

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and 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.
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
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
no effects observed
Description (incidence and severity):
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 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.

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Dose descriptor:
NOEL
Generation:
F1
Effect level:
180 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
body weight and weight gain
other: overall developmental effects
Remarks on result:
other: no overall developmental effects obseved

Target system / organ toxicity (F1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
In reproductive 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 reproductive and developmental toxicity study ofBasic 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 femalewistar rats treated withBasic Red 51 (77061-58-6)via oral gavage for days 6 to 17 post coitum.