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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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1984

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: FDA and Tolitet Goods Association
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:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium 4-[(2-hydroxy-1-naphthyl)azo]benzenesulphonate
EC Number:
211-199-0
EC Name:
Sodium 4-[(2-hydroxy-1-naphthyl)azo]benzenesulphonate
Cas Number:
633-96-5
Molecular formula:
C16H12N2O4S.Na
IUPAC Name:
sodium 4-[(2-hydroxy-1-naphthyl)azo]benzenesulphonate

Test animals

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.

Administration / exposure

Type of coverage:
open
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.
Doses / concentrations
Remarks:
Doses / Concentrations:
0.1 ml containing 1% of the tested substance
Basis:
nominal per unit body weight
No. of animals per sex per dose:
600 mice for test, 700 mice for control
Control animals:
yes, concurrent vehicle

Examinations

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.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
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:
not specified
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
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

Effect levels

Dose descriptor:
NOAEL
Effect level:
other: no data
Basis for effect level:
other: No data
Remarks on result:
not determinable
Remarks:
no NOAEL identified

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
No adverse reactions or pathological changes were observed following weekly dermal applications for 18 months to the dorsal area of Swiss-Webster. The calculated NOAEL is 30 mg/kg bw weekly which correspond to a 4.29 mg/kg bw/day.
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.