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

Carcinogenicity

Description of key information

No indication of carcinogenic properties was observed in a skin painting study in mice with 50 mg/kg bw of Pigment Red 57:1 (Carson 1984).

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1961 -1969

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

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.

Qualifier:

according to guideline

Guideline:

other: protocol agreed between the U.S. Food and Drug Agency and CTFA

Principles of method if other than guideline:

Dermal application onto shaved mouse skin twice weekly for 18 months.

GLP compliance:

no

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%
- Lot/batch No.: W4602

Species:

mouse

Strain:

ICR

Remarks:

Swiss Webster derived

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: ad libitum
- Water:ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS: no data

Route of administration:

dermal

Vehicle:

water

Details on exposure:

- Application volume: 0.1 mL of a 1% suspension in water;
- Application site: doral, applied with an automatic syringe and distributed on the skin with a rubber applicator over a surface of 6 cm2
- Time intervals for shavings or clipplings: 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

Post exposure period:

none

Dose / conc.:

1 other: mg/mouse

Remarks:

corresponding to 0.166 mg/cm2 (nominal); 50 mg/kg bw/day (nominal)

No. of animals per sex per dose:

- Test substance: 50
- Control: 150
- Positive control: 50

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

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily

DERMAL IRRITATION: 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

Clinical signs:

not specified

Mortality:

mortality observed, non-treatment-related

Description (incidence):

No effects in comparison to the control

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

- Extramedullary ematopoiesis was found in the spleen, although this was consistent with the vehicle control group and therefore considered not treatment-related.
- Lesions that were observed in several organs could alsno not be attributed to exposure to the test material.

Histopathological findings: neoplastic:

no effects observed

Description (incidence and severity):

No apparent change in number of neoplasias, such as in the mammary glands or internal organs, that was attributable to the test material when compared to the control.

Other effects:

effects observed, treatment-related

Description (incidence and severity):

Ectoparasitism was greater than that in the control group, that may have contributed to epidermal changes.

Dose descriptor:

NOAEL

Effect level:

>= 0.17 other: mg/cm2; corresponds to 1 mg per mouse or roughly 50 mg/kg bw

Sex:

male/female

Basis for effect level:

other: no adverse effects observed

In the mid-1960s a number of cosmetic color additives originally identified by US Food and Drug Administration and the Cosmetic, Toiletry and Fragrance Association (CTFA) (formerly the Toilet Goods Association) were evaluated as part of an overall program to determine safety for human usage in a series of coal tar derived colors which were then in wide use by the cosmetic, drug and food industries.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. Because, no carcinogenicity has been observed and the substance is also not genotoxic, the substance is not considered to be classified for carcinogenicity according to Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008.

Additional information

Skin painting

No indication of carcinogenic properties was observed in a skin painting study in mice with Pigment Red 57:1(CA) (Carson 1984). The investigation was performed prior to introduction of GLP. Limited details are given in the literature publication. The study was designed by the US competent authority and an industry association to assess the safety of the use in lipstick. For 18 months, mice were given 0.1 ml of an aqueous solution of 1% onto an area of 6 cm2 twice per week. This corresponds to a dose of 1 mg per mouse (50 mg/kg bw) per treatment. Full histopathology was only performed for 5 of 50 animals per dose group.