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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 is from secondary source

Data source

Reference
Reference Type:
secondary source
Title:
Teratogenicity study for Acid Violet 43
Author:
Scientific Committee on Consumer Safety SCCS
Year:
2013
Bibliographic source:
OPINION ON Acid Violet 43 COLIPA n° C63, 2013

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: OECD 414
Principles of method if other than guideline:
Prenatal Development Toxicity Study of Acid Violet 43 in rat
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonate
EC Number:
224-618-7
EC Name:
Sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonate
Cas Number:
4430-18-6
Molecular formula:
C21H14NNaO6S
IUPAC Name:
sodium 2-[(4-hydroxy-9,10-dioxo-9,10-dihydroanthracen-1-yl)amino]-5-methylbenzenesulfonate
Test material form:
solid: particulate/powder
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
Specific details on test material used for the study:
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
Sex:
female
Details on test animals or test system and environmental conditions:
not specified

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:
not specified
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 / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
94 mg/kg bw/day
Dose / conc.:
282 mg/kg bw/day
Dose / conc.:
940 mg/kg bw/day
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:
not specified
Positive control:
not specified

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):
not specified
Sperm parameters (parental animals):
not specified
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:
not specified
Reproductive indices:
not specified
Offspring viability indices:
not specified

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
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
Description (incidence):
No mortality was 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 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 to be incidental as a dose relation was missing.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
940 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
reproductive performance
Remarks on result:
other: No effect 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:
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):
No effect on foetuses weight were observed as compared to control.
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 external anomalies were observed in foetuses.
Histopathological findings:
no effects observed
Description (incidence and severity):
No soft tissue and skeletal anomalies were observed in foetuses as compered to control.
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

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:
body weight and weight gain
gross pathology
histopathology: non-neoplastic
Remarks on result:
other: No effect 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 for P and F1 generation when Wistar female rats were treated with Acid Violet 43 orally by gavage through day 6-17 of gestation.

Executive summary:

In a reproductive toxicity study, Wistar female rats were treated with Acid Violet 43 in the concentration of0, 94, 282 or 940mg /kg bw/day through day 6-17 of 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. Discoloured faeces were observed at 940 mg/kg bw/day. No mortality was observed in treated female rat. Similarly, 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 to be incidental as a dose relation was missing. In addition, No effect on foetuses weight and noexternal, soft tissue and skeletal anomalies were observed as compared to control. Therefore, NOAEL was considered to be 940 mg/kg bw for P and F1 generation whenWistar female rats were treated with Acid Violet 43 orally by gavage through day 6-17 of gestation.

 

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