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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Performed prior to introduction of GLP. Limited details reported. Designed mainly to detect skin cancer. Full histopathology only performed for 5 of 50 animals per dose group.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Skin Painting Studies in Mice with 14 FD&C and D&C Colors
Author:
Carson S
Year:
1984
Bibliographic source:
J. Toxicol. - Cut. and Ocular Toxicol. 3 (4), 357 - 370

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
18 months application twice weekly of 50 mg/kg bw onto shaved skin of mice with histopathology of skin and major organs
GLP compliance:
no
Limit test:
yes

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:
- 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:
- 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 animals

Species:
mouse
Strain:
ICR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: not applicable
- Housing: single
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
no data

Administration / exposure

Type of coverage:
not specified
Vehicle:
water
Details on exposure:
Application of 0.1 ml of a 1% suspension in water
application site: 6 cm2

Initially. the hair on the dorsal area of each animal was clipped with an animal clipper free of lubricatirig oil. Subsequent periodic clipping was performed according to the rate of hair growth.

The test item suspension was prepared fresh weekly
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
471 days (ca 18 months)
Frequency of treatment:
twice per week
Doses / concentrations
Dose / conc.:
0.166 mg/cm² per day (nominal)
No. of animals per sex per dose:
50 for test item
150 for control
50 for positive control
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: Based on human exposure from use in lipstick

Positive control:
3,4-benzpyrene, dissolved in acetone

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations not included

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily
DERMAL IRRITATION (if dermal study): No data
BODY WEIGHT: No data
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: No data
CLINICAL CHEMISTRY: No data
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (preparation of: brain, pituitary, thyroid, thymus, liver, spleen, kidney, adrenal, stomach, small and large intestines, urinary bladder, axillary lymph nodes, testes, ovary, skin from area of treatment, any tissue massess, grossly abnormal organs; complete pathology only for each five males and females; skin and grossly abnormal organs for all animals)
Statistics:
no data

Results and discussion

Results of examinations

Details on results:
No test-item related effects were observed.

Effect levels

Dose descriptor:
NOEL
Effect level:
>= 50 other: mg/kg bw twice weekly
Based on:
test mat.
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion