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Description of key information

No adverse reactions or pathological changes were observed following weekly dermal applications for 18 months to the dorsal area of Swiss-Webster.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
other: FDA and Tolitet Goods Association
Deviations:
not specified
Principles of method if other than guideline:
The protocol for the series of tests carried out between 1961 and 1969 was agreed on and utilized after direct consultation with the Food and Drug Administration.
The study design followed was prepared by the late Dr. Arnold J. Lehman of the Food and Drug Administration and was considered to be appropriate testing procedure for assessing the carcinogenic properties of these color materials.
GLP compliance:
not specified
Species:
mouse
Strain:
Swiss Webster
Sex:
male/female
Details on test animals or test system and environmental conditions:
Seventeen hundred Swiss-Webster mice with an initial weight ranging from 17 to 25 g were used in this study.
All groups were equally divided as to sex.
Mice of the same sex were housed five per cage and were allowed free access to pellets of Purina Laboratory Chow and fresh water.
Route of administration:
dermal
Vehicle:
water
Details on exposure:
The hair on the dorsal area of each animal was clipped with an animal clipper free of lubricating oil. Subsequent periodic clipping was performed
according to the rate of hair growth. An area of approximately 6 cm2 was treated twice weekly.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
18 months
Frequency of treatment:
Once each week for the duration of the study 0.1 ml of the solvent or of the color solution containing 1.0% of the respective color was applied to the depilated area of the mice.
No. of animals per sex per dose:
600 mice for test, 700 mice for control
Control animals:
yes, concurrent vehicle
Observations and examinations performed and frequency:
The animals were observed daily for behaviour, survival and visible or palable growth.
Sacrifice and pathology:
All surviving animals were terminated after approximately 18 months, when a marked increase of geriatric mortality became apparent.
All mice were necropsied after they died or were sacrificed.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Relevance of carcinogenic effects / potential:
There was no indication of treatment related pathology since most lesions were also evident in the controls.
The test was considered appropriate for assessing the carcinogenic properties of the color additives.
All lymphomas, lymphomatous infiltrates, and leukemic infiltrates have been grouped under the term “lymphoma”.
Such changes are considered to be a single type of spontaneous neoplasia in mice which may show a range of cytological variations.
There was no significant difference in the incidence of this lesion among the groups. In the experience of the testing laboratory, 1ymphoJnatous neoplasias of some degree occur in almost all albino Swiss-Webster mice that die between 5 and 12 months of age, without regard to treatment.
There was no indication of treatment related pathology since most lesions were also evident in the controls.
No adverse reactions or pathological changes were observed following weekly dermal applications for 18 months to the dorsal area of Swiss-Webster.

No effect on growth, behavior, or survival indicative of a dose related effect was observed.

All lymphomas, lymphomatous infiltrates, and leukemic infiltrates have been grouped under the term “lymphoma”.

Such changes are considered to be a single type of spontaneous neoplasia in mice which may show a range of cytological variations.

There was no significant difference in the incidence of this lesion among the groups. In the experience of the testing laboratory, 1ymphoJnatous neoplasias of some degree occur in almost all albino Swiss-Webster mice that die between 5 and 12 months of age, without regard to treatment.

There was no indication of treatment related pathology since most lesions were also evident in the controls.

No adverse reactions or pathological changes were observed following weekly dermal applications for 18 months to the dorsal area of Swiss-Webster.

Conclusions:
No adverse reactions or pathological changes were observed following weekly dermal applications for 18 months to the dorsal area of Swiss-Webster.
Executive summary:

No effect on growth, behavior, or survival indicative of a dose related effect was observed.

Repeated twice weekly applications of solution or suspensions of the eleven cosmetic color additives to the skin of depilated mice produced no significant incidence of gross or histopathological changes.

Macroscopic and microscopic observations revealed only such lesions as are common in geriatric mice, with equal frequency and degree in both treated and control animals.

The findings in this series of skin painting studies more clearly denote administration limited to topical administration minimizing or delimiting oral exposure. Every effort was made to place these dyes in an area with limited oral access during preening activity.

The findings described above appear to indicate freedom from significant systemic and/or dermal toxic manifestations associated with these administrations. All lymphomas, lymphomatous infiltrates, and leukemic infiltrates have been grouped under the term “lymphoma”.

Such changes are considered to be a single type of spontaneous neoplasia in mice which may show a range of cytological variations.

There was no significant difference in the incidence of this lesion among the groups. In the experience of the testing laboratory, 1ymphoJnatous neoplasias of some degree occur in almost all albino Swiss-Webster mice that die between 5 and 12 months of age, without regard to treatment.

There was no indication of treatment related pathology since most lesions were also evident in the controls.

No adverse reactions or pathological changes were observed following weekly dermal applications for 18 months to the dorsal area of Swiss-Webster.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Study duration:
chronic
Species:
mouse

Justification for classification or non-classification

There was no indication of treatment related pathology since most lesions were also evident in the controls.

Additional information

All lymphomas, lymphomatous infiltrates, and leukemic infiltrates have been grouped under the term “lymphoma”.

Such changes are considered to be a single type of spontaneous neoplasia in mice which may show a range of cytological variations.

There was no significant difference in the incidence of this lesion among the groups. In the experience of the testing laboratory, limphomatous neoplasias of some degree occur in almost all albino Swiss-Webster mice that die between 5 and 12 months of age, without regard to treatment.

Justification for selection of carcinogenicity via dermal route endpoint:

The test was considered appropriate for assessing the carcinogenic properties of the color additives.