1,4-bis[(2-methylphenyl)amino]anthraquinone

Toxicity to reproduction

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

Test material information

Constituent 1

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 / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day

Doses / concentrations 2

Dose / conc.:

94 mg/kg bw/day

Doses / concentrations 3

Dose / conc.:

282 mg/kg bw/day

Doses / concentrations 4

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.