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Toxicological information

Developmental toxicity / teratogenicity

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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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Little reporting details on animals, test item and results. Highest dose is only 50 mg/kg bw and no maternal toxicity mentioned.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1972
Report date:
1972
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
Reference Type:
publication
Title:
Unnamed
Year:
1974

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
GLP compliance:
no
Remarks:
pre-dates GLP requirements
Limit test:
no

Test material

Constituent 1
Chemical structure
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:
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 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 / concentrationsopen allclose all
Dose / conc.:
5 mg/kg bw/day (actual dose received)
Dose / conc.:
16 mg/kg bw/day (actual dose received)
Dose / conc.:
50 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
- Control: two groups, each with 22 females
- Test group: 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

General toxicity (maternal animals)

Body weight and weight changes:
no effects observed
Description (incidence and severity):
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.

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Effect level:
>= 50 mg/kg bw/day
Basis for effect level:
other: no adverse effects observed

Maternal abnormalities

Abnormalities:
not specified

Results (fetuses)

Details on embryotoxic / teratogenic effects:
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 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.

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Remarks:
teratogenicity
Effect level:
>= 50 mg/kg bw/day
Basis for effect level:
other: no adverse effects observed

Fetal abnormalities

Key result
Abnormalities:
no effects observed

Overall developmental toxicity

Key result
Developmental effects observed:
no

Applicant's summary and conclusion