2-methylanthraquinone

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 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

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

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

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 or test system 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.