4,4'-carbonimidoylbis[N,N-diethylaniline] monohydrochloride

Toxicity to reproduction

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 is from assessment report

Data source

Reference

Reference Type:

secondary source

Title:

OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING ACID RED 52

Author:

THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS (SCCNFP)

Year:

2004

Bibliographic source:

THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS (SCCNFP) /0803/ 23 April 2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Female rats were administered Acid Red 52 by gavage for examining its Reproductive/Developmetal toxicity potential.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Hydrogen 3,6-bis(diethylamino)-9-(2,4-disulphonatophenyl)xanthylium, sodium salt

EC Number:

222-529-8

EC Name:

Hydrogen 3,6-bis(diethylamino)-9-(2,4-disulphonatophenyl)xanthylium, sodium salt

Cas Number:

3520-42-1

Molecular formula:

C27H30N2O7S2.Na

IUPAC Name:

sodium 4-[3,6-bis(diethylamino)-2,7-dimethylxanthenium-9-yl]benzene-1,3-disulfonate; 2-(3-diethylamino-6-diethylazaniumylidene-xanthen-9-yl)-5-sulfo-benzenesulfonate

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report):Acid Red 52
- Molecular formula : C27H30N2O7S2.Na
- Molecular weight : 580.6551 g/mol
- Substance type:Organic
Physical State: Solid

Specific details on test material used for the study:

- Name of test material (as cited in study report): Acid Red 52
- Molecular formula : C27H30N2O7S2.Na
- Molecular weight : 580.6551 g/mol
- Substance type: Organic
- Physical state: solid
- Impurities (identity and concentrations): 80% (± 3%)

Test animals

Species:

rat

Strain:

Wistar

Details on species / strain selection:

not specified

Sex:

female

Details on test animals or test system and environmental conditions:

not specified

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: (bi-distilled water containing 1% carboxymethyl cellulose sodium salt

Details on exposure:

not specified

Details on mating procedure:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

20 dyas

Frequency of treatment:

daily

Details on study schedule:

not specified

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

300 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5 females / dose level

Control animals:

yes

Details on study design:

not specified

Positive control:

not specified

Examinations

Parental animals: Observations and examinations:

Clinical signs

Oestrous cyclicity (parental animals):

not specified

Sperm parameters (parental animals):

not specified

Litter observations:

not specified

Postmortem examinations (parental animals):

the animals were killed and examined macroscopically. Foetuses were removed by Caesarean section.

Postmortem examinations (offspring):

not specified

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:

effects observed, non-treatment-related

Description (incidence and severity):

Violet discoloured faeces, urine and bedding material were noted from day 7 post coitum till day 19 post coitum in all treatment groups, no reaction to treatment or clinical signs were observed in any female.

Dermal irritation (if dermal study):

not specified

Mortality:

no mortality observed

Description (incidence):

No death occurred during the course of the study.

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

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):

The relevant maternal reproductive data (mean number of implantations and live foetuses) were similar in all groups. No external abnormalities were noted in any of the foetuses. The sex ratios were similar in all groups.

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

clinical signs

mortality

reproductive function (sperm measures)

Target system / organ toxicity (P0)

Critical effects observed:

not specified

Results: F1 generation

Effect levels (F1)

Remarks on result:

other: not specified

Target system / organ toxicity (F1)

Critical effects observed:

not specified

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Based on the results described above, 1000 mg/kg bw/day of sodium 4-[3,6-bis(diethylamino)-2,7-dimethylxanthenium-9-yl]benzene-1,3-disulfonate (Acid Red 52) is considered to be the No-Observable-Adverse-Effect-Level (NOAEL) for the maternal/ reproductive toxicity.

Executive summary:

Three groups of five mated female rats were administered Acid Red 52 by gavage at doses of 100, 300 or 1000 mg/kg bw/day from day 6 through day 17 post coitum. An additional group of five mated rats was administered the vehicle (bi-distilled water containing 1% carboxymethyl cellulose sodium salt) and served as a control group. On day 21 post coitum, the animals were killed and examined macroscopically. Foetuses were removed by Caesarean section. No death occurred during the course of the study. Violet discoloured faeces, urine and bedding material were noted from day 7 post coitum till day 19 post coitum in all treatment groups. The relevant maternal reproductive data (mean number of implantations and live foetuses) were similar in all groups. No external abnormalities were noted in any of the foetuses. The sex ratios were similar in all groups. Based on the results described above, 1000 mg/kg bw/day of sodium 4-[3,6-bis(diethylamino)-2,7-dimethylxanthenium-9-yl]benzene-1,3-disulfonate (Acid Red 52) is considered to be the No-Observable-Adverse-Effect-Level (NOAEL) for the maternal/ reproductive toxicity.