Barium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1972

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non GLP, little reporting details on animals, test item and results. Highest dose is only 50 mg/kg bw and no maternal toxicity mentioned.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1972

Report date:

1972

Reference 2

Reference Type:

review article or handbook

Title:

Toxicity Profile for Lithol Rubine BK

Author:

Anonymous

Year:

1993

Bibliographic source:

BIBRA Information and Advisory Service, BIBRA Toxicology International, Carshalton, Surrey, SM5 4DS Great Britain

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

low dose, limited investigations regarding maternal toxicity. No individual data, no statistical evaluation

Principles of method if other than guideline:

teratogenicity study in rabbits

GLP compliance:

no

Remarks:

pre-dates GLP requirements

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate

EC Number:

226-109-5

EC Name:

Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate

Cas Number:

5281-04-9

Molecular formula:

C18H14N2O6S.Ca

IUPAC Name:

calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate

Test material form:

solid: nanoform

Details on test material:

- Name of test material (as cited in study report): D&C Red 7
- Substance type: pigment
- Physical state: solid
- Analytical purity: 98%
- Impurities (identity and concentrations): no data
- Purity test date: no data
- Lot/batch No.: W4602
- Expiration date of the lot/batch: no data

Test materials used in this dossier are all considered to fall under the definition of nano-materials according to the European Commission Recommendation 2011/696/EU as the synthesis and manufacturing of this pigment always yields particulate material with a fine particle size distribution.

Specific details on test material used for the study:

D&C Red No. 7 (FDA Certification no. Y W4502)

Test materials used in this dossier are all considered to fall under the definition of nano-materials according to the European Commission Recommendation 2011/696/EU as the synthesis and manufacturing of this pigment always yields particulate material with a fine particle size distribution.

Test animals

Species:

rat

Strain:

other: CD

Details on test animals or test system and environmental conditions:

Male and female CD rats were obtained from Tthe Charles River Breeding Laboratory an weanlings, the males assigned numerical identification at random and placed in individual hanging cages until they reached a satisfactory age for mating. The diet consisted of Puriria Laboratory Chow.
Body weight of dams of gestation ranged between 213 and 292 g on day 0.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% methylcellulose

Details on exposure:

Volumes of 10, 3-2, and 1 ml/kg were used with all controls receiving a volume of 10 ml/kg.

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

Mating was accomplished by pairing one female with one male. The appearance of a vaginal plug was taken as evidence of satisfactory mating and this was counted as day zero of gestation.

Duration of treatment / exposure:

day 6-15 of pregnancy

Frequency of treatment:

daily

Duration of test:

Dams wew sacrificied on day 20 of gestation ander chloroform anaesthesia.

Doses / concentrations

Remarks:

Doses / Concentrations:
5, 16, 50 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

control: two groups, each with 22 females
test substance: 22 females per dose group

Control animals:

yes, concurrent vehicle

Details on study design:

Acetylsalicylic acid (aspirin, 250 mg/kg bw) was used as positive control.

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: No data


DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: days 0, 6, 15 and 20 of gestation


POST-MORTEM EXAMINATIONS: No
- Sacrifice on gestation day 20

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No, but total litter weight determined
- Number of corpora lutea: No
- Number of implantations: Yes
- Number of resorptions: Yes (no difference made for early or late)
- Other: number of dead and live fetuses were recorded, sex distribution was recorded.

Fetal examinations:

- External examinations: Yes
- Soft tissue examinations: Yes: one third per litter
- Skeletal examinations: Yes: two thirds per litter
- Head examinations: No data
- fetal weight: determined per litter litter

Statistics:

none

Indices:

none

Historical control data:

The results were compared to historical control data, but no actual historical control data is included in the report.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Body weight gain was not affected.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

>= 50 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

>= 50 mg/kg bw/day

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

no effects observed

Overall developmental toxicity

Developmental effects observed:

no

Any other information on results incl. tables

Groups of ten females given 5, 16 or 50 mg/kg bw/day by stomach tube on days 6-15 of pregnancy showed no adverse effects on maternal weight gain, number of resorptions, litter size, foetal weight and viability, or the incidence of foetal malformations. Animals of the positive control group (aspirin at 250 mg/kg bw) showed the expected malformations.

Applicant's summary and conclusion

Conclusions:

No developmental toxicity was observed in rats at doses of 5, 16 and 50 mg/kg bw.