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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
one-generation reproductive 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:
Teratogenicity study of test material
Author:
Scientific Committee on Consumer Safety SCCS
Year:
2013
Bibliographic source:
OPINION ON TEST MATERIAL, 2013

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD 414
Principles of method if other than guideline:
Prenatal Development Toxicity Study of test material was performed in rats.
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 (as cited in study report):Ext. D&C Violet n° 2/ Acid Violet 43
Molecular formula : C21H14NO6S, Na
Molecular weight : 431.4 g / mole
Smiles notation : c12c(C(c3ccccc3C2=O)=O)c(ccc1Nc1c(cc(C)cc1)S(=O)(=O)[O])O.[Na+]
InChl (if other than submission substance): 1S/C21H15NO6S.Na/c11-1-6-7-14(17(10-11)29(26,27)28)22-15-89-16 (23)19-18(15)20(24)12-4-23-5-13(12)21(19)25;/h2-10,22-23H,1H3,(H,26,27,28);/q;+1/p1
Substance type: Organic
Physical state: Solid

Test animals

Species:
rat
Strain:
Wistar
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
Type of inhalation exposure (if applicable):
not specified
Vehicle:
other: 1% carboxymethylcellulose in water
Details on exposure:
- Concentration in vehicle: 0, 100, 300 and 1000 mg/kg bw/day (0, 94, 282 or 940 mg active dye/kg bw/day)
- Amount of vehicle (if gavage): 10 ml/kg
Details on mating procedure:
No data available
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
12 days (6-17 of gestation period)
Frequency of treatment:
Daily
Details on study schedule:
A prenatal developmental study was conducted on female Wistar rats.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 100, 300 and 1000 mg/kg bw/day (0, 94, 282 or 940 mg active dye/kg bw/day)
Basis:
no data
No. of animals per sex per dose:
Total number of animals-88
0 mg /kg bw/day -22 female rats
94 mg /kg bw/day -22 female rats
282 mg /kg bw/day -22 female rats
940 mg /kg bw/day-22 female rats
Control animals:
yes, concurrent vehicle
Details on study design:
No data
Positive control:
No data

Examinations

Parental animals: Observations and examinations:
Parental animal: observation and examination- Clinical sign, body weight and food intake was observed.
Histopathology- About one half of the foetuses were examined for soft tissue anomalies whereas remaining foetuses were examined for skeletal anomalies following alizarin red staining.



Oestrous cyclicity (parental animals):
No data

Sperm parameters (parental animals):
No data
Litter observations:
Foetuses were sexed and weighed.
Postmortem examinations (parental animals):
Embryonic resorptions and implantation sites was observed.
Postmortem examinations (offspring):
Foetuses were observed externely.
Statistics:
No data
Reproductive indices:
No data
Offspring viability indices:
No data

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
effects observed, non-treatment-related
Description (incidence and severity):
Discoloured faeces were observed at 940 mg/kg bw/day.
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
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
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):
At the does group of 940mg /kg bw/day one female had only embryonic resorptions.At the dose group of 282 and 940 mg /kg bw/day two
Females were not pregnant, one female had only empty implantation sites and a further one only embryonic resorptions at Caesarean section. These findings were considered by the study authors to be incidental as a dose relation was missing

Details on results (P0)

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)-No mortality was observed.Clinical sign- Discoloured faeces were observed at 940 mg/kg bw/day.

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)-No data available

TEST SUBSTANCE INTAKE (PARENTAL ANIMALS)-No data available

REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS)-No data available

REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS)-No data available

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)-No data available

ORGAN WEIGHTS (PARENTAL ANIMALS)-No data available

GROSS PATHOLOGY (PARENTAL ANIMALS)-At the does group of 94 mg /kg bw/day one female had only embryonic resorptions.
At the dose group of 282 and 940 mg /kg bw/day two
Females were not pregnant, one female had only empty implantation sites and a further one only embryonic resorptions at Caesarean section.

HISTOPATHOLOGY (PARENTAL ANIMALS)-No data available

OTHER FINDINGS (PARENTAL ANIMALS)-No data available

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
940 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Maternal toxicity was not observed at all dose level.
Remarks on result:
other: overall no effects on reproductive performance was observed

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:
no effects observed
Description (incidence and severity):
No significannt change were observed in treated group compare to control group.
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No significannt change were observed in treated group compare to control group.
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:
no effects observed
Description (incidence and severity):
No significant change was observed on external soft tissue and skeletal anomalies based in treated group compare to control group .
Histopathological findings:
no effects observed
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Details on results (F1)

VIABILITY (OFFSPRING)-No data available

CLINICAL SIGNS (OFFSPRING)-No significannt change were observed in treated group compare to control group.

BODY WEIGHT (OFFSPRING)-No significannt change were observed in treated group compare to control group.

SEXUAL MATURATION (OFFSPRING)-No data available

ORGAN WEIGHTS (OFFSPRING)-No data available

GROSS PATHOLOGY (OFFSPRING)-No significant change was observed on external soft tissue and skeletal anomalies based in treated group compare to control group .

HISTOPATHOLOGY (OFFSPRING)-No data available

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
940 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant change were observed on litter parameters and foetal weight. No significant change were observed on external soft tissue and skeletal anomalies in treated group compare to control group
Remarks on result:
other: overall no developmental toxic effects observed

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:
NOAEL was considered to be 940 mg /kg bw/day for reproductive toxicity in P0 female Wistar rats , when they were exposed with test material at the concentration of 0, 94, 282 or 940 mg /kg bw/day through 6-17 of gestation period by oral (gavage).
Executive summary:

Reproductive toxicity study was observed for test material in P0 female Wistar rats, when they were  exposed at the concentration of 0, 94, 282 or 940mg /kg bw/day through  6-17of gestation period by oral (gavage).The test substance (in1%carboxymethylcellulose in water) was given daily at dose volumes of 10 ml/kg bw by oral gavage. Dams were observed daily for clinical signs, body weight and food intake recorded at designated intervals. The females were killed on gestation day 21, subjected to macroscopic examination, and foetuses were removed by Caesarean section. Common litter parameters were recorded and foetuses were sexed, weighed and submitted to external examination. About one half of the foetuses were also examined for soft tissue anomalies where as remaining foetuses were examined for skeletal anomalies following alizarin red staining. At the does group of 94 mg /kg bw/day one female had only embryonic resorptions.

At the dose group of 282 and 940 mg /kg bw/day two Females were not pregnant, one female had only empty implantation sites and a further one only embryonic resorptions at Caesarean section. These findings were considered by the study authors to be incidental as a dose relation was missing.No mortality was observed. Discoloured faeces were observed at 940mg/kg bw/day. No significant changes were observed on litter parameters and fetal weight. No significant changes were observed on external soft tissue and skeletal anomalies in treated group compare to control. Therefore NOAEL was considered to be 940 mg /kg bw/day for test material in P0 female Wistar rats.