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Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1962
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Unknown purity, old and not very well described method, Not GLP
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
GLP compliance:
no
Species:
rat
Sex:
male/female
Route of administration:
oral: feed
Duration of treatment / exposure:
90 days
Frequency of treatment:
in diet
Remarks:
Doses / Concentrations:1% Basis:nominal in diet
Remarks:
Doses / Concentrations:5% Basis:nominal in diet
No. of animals per sex per dose:
10 at 1%, 5 at 5%
Control animals:
yes, plain diet
Dose descriptor:
LOAEL
Effect level:
ca. 10 000 mg/kg diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: toxic effect in kidney and spleen
Critical effects observed:
not specified
Conclusions:
LOAEL < 10,000 mg/kg diet
Executive summary:

Ten male and ten female rats per group were exposed to C.I. Pigment Red 4 in the diet for 90 days at two concentrations of 5% and 1%. 

No rats died during the study. The general behavior of rats at 5% and 1% was not affected. The body weight gain was lower in the 5% group compared to controls for male rats. Body weight gain of female rats at 5% concentration of test substance in the diet were not affected.

The histological examination of the organs did show some signs of changes related to the experiment in the kidney and spleen when exposed to 1% of C.I. Pigment Red 4 and more prominently at 5%.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEL
500 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1984
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Based on the limited reporting, the limited number of organs investigated as well as the study design it is not possible to assess the validity of the study.
Species:
mouse
Sex:
male/female
Vehicle:
water
Duration of treatment / exposure:
18 month
Frequency of treatment:
2 times a week
Remarks:
Doses / Concentrations:0.1 mL 1% suspension of test itemBasis:
No. of animals per sex per dose:
50
Dose descriptor:
NOAEL
Effect level:
> 0.05 mg/cm² per day (nominal)
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable
Remarks:
no NOAEL identified
Critical effects observed:
not specified
Executive summary:

A series of 14 cosmetic colors were submitted to dermal toxicity testing in accordance with a protocol designed by the Food and Drug Administration and agreed upon with the Cosmetic, Toiletry and Fragrance Association (formerly the Toilet Goods Association). Dosage levels were based on lipstick use determinations made in a group of human female volunteers. The groups of lipstick colors were divided into three treatment series and painted on twice weekly to an area approximately 6 cm2. A total of 1400 mice were used comprising groups of 100 mice (50 per sex) plus additional positive control group of the same size and a vehicle control group of 300 mice (150 per sex). All colors were prepared at 1.0% suspensions in water. The positive control received 3.4–benzpyrene dissolved in acetone. Survival was approximately equivalent in all experimental groups except the positive controls who died earlier consistent with survival recorded by others for 3.4–benzpyrene treated mice. Extramedullary hematopoesis was found in all treated groups, equivalent to the findings in the controls. The repeated application of 0.1 ml containing 1.0% dye did not increase the incidence of neoplasia when compared to controls in any of the groups receiving application of the 14 dyes.

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1984
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Based on the limited reporting, the limited number of organs investigated as well as the study design it is not possible to assess the validity of the study.
Species:
mouse
Sex:
male/female
Vehicle:
water
Duration of treatment / exposure:
18 month
Frequency of treatment:
2 times a week
Remarks:
Doses / Concentrations:0.1 mL 1% suspension of test itemBasis:
No. of animals per sex per dose:
50
Dose descriptor:
NOAEL
Effect level:
> 0.05 mg/cm² per day (nominal)
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable
Remarks:
no NOAEL identified
Critical effects observed:
not specified
Executive summary:

A series of 14 cosmetic colors were submitted to dermal toxicity testing in accordance with a protocol designed by the Food and Drug Administration and agreed upon with the Cosmetic, Toiletry and Fragrance Association (formerly the Toilet Goods Association). Dosage levels were based on lipstick use determinations made in a group of human female volunteers. The groups of lipstick colors were divided into three treatment series and painted on twice weekly to an area approximately 6 cm2. A total of 1400 mice were used comprising groups of 100 mice (50 per sex) plus additional positive control group of the same size and a vehicle control group of 300 mice (150 per sex). All colors were prepared at 1.0% suspensions in water. The positive control received 3.4–benzpyrene dissolved in acetone. Survival was approximately equivalent in all experimental groups except the positive controls who died earlier consistent with survival recorded by others for 3.4–benzpyrene treated mice. Extramedullary hematopoesis was found in all treated groups, equivalent to the findings in the controls. The repeated application of 0.1 ml containing 1.0% dye did not increase the incidence of neoplasia when compared to controls in any of the groups receiving application of the 14 dyes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Most sensitive species with the lowest LOAEL

Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: spleen; urogenital: kidneys

Justification for classification or non-classification