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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Not enough details of experimental procedure for an evaluation of the study.

Data source

Reference
Reference Type:
publication
Title:
Short-term toxicity tests on the mono and di methyl ethers of hydroquinone
Author:
Hodge HC, Sterner JH, Maynard EA, Thomas J.
Year:
1949
Bibliographic source:
J. Ind. Hyg. Toxicol. 31, 79-92.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Subacute toxicity by dermal application
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no data

Test animals

Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no data

Administration / exposure

Type of coverage:
not specified
Vehicle:
other: sun tan lotion
Details on exposure:
TEST SITE
- Area of exposure: the areas of the skin on the back and sides of the rabbits were prepared by clipping the fur and then applying a depilatory.
- % coverage: no data
- Type of wrap if used: no data

REMOVAL OF TEST SUBSTANCE
- Washing (if done): unwashed
- Time after start of exposure: no data

TEST MATERIAL
- Amount(s) applied: 5 ml of sun tan lotion base prepared on two basic formulae.
One contained the specified amount of PDMB (1g or 10g), 5 g of castor oil, 6 g of water and alcohol to make 100 g.
The other formula contained the specified amount of PDMB (1g or 10g), 15 g of butyl stearate, and alcohol to make 100 g.
- concentration (if solution): 1% or 10%

VEHICLE: sun tan lotion
2 different formulations: One contained the specified amount of PDMB, 5 g of castor oil, 6 g of water and alcohol to make 100 g. The other formula contained the specified amount of PDMB, 15 g of butyl stearate, and alcohol to make 100 g.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
30 days
Frequency of treatment:
5 days a week.
Doses / concentrations
Remarks:
Doses / Concentrations:
5 ml of solution at 1 and 10% in sun tan lotion
Basis:
other: 2 different formulations
No. of animals per sex per dose:
6 animals per dose group (sex unspecified)
Control animals:
other: yes, animals received sun tan lotion preparation
Details on study design:
no data
Positive control:
no data

Examinations

Observations and examinations performed and frequency:
* CAGE SIDE OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
MORTALITY: Yes
- Time schedule for examinations: no mortality during the test
ORGAN WEIGHT: YES (heart, lungs, spleen, liver, kidneys, brain, stomach, testes)
FOOD CONSUMPTION: No data
WATER CONSUMPTION: No data
CLINICAL SIGNS: No data
FUNCTIONAL OBSERVATIONS: No data
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for examinations: at begin, middle after 2 weeks and the end of study (4 weeks)
- Animals fasted: No data
- Parameters: haemoglobin concentration / erythrocyte count / total leukocyte count / differential leukocyte count /
CLINICAL CHEMISTRY: No
- Animals fasted: No data
- Parameters: No data
URINALYSIS: Yes
- Time schedule for examinations: prior to, mid way and at the end of the study.
- Parameters: protein / sugar
Sacrifice and pathology:
yes
Other examinations:
no data
Statistics:
no data

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Details on results:
Loss of some organ weights.

No mortality during the study.
WEIGHT: there were no changes in body weights during the study.

URINALYSIS: no significant values.

HEMATOLOGY: all the hematological findings were within normal limits.

PATHOLOGY: no toxic reaction, except some tendency to decrease in testes weights, was observed and the spleen weights showed a tendency to increase. A gross pitting of the kidney surface was observed in 2 of the 1% treated animals and 3 of the 10%.
A large spleen was observed in 2 animals treated at 1%.

Principal changes were seen in the examination of the skin: grossly in both control and experimental animals, dryness and crusting of the surface was observed. Microscopic changes ranging from atrophy of the epidermis to ulceration and inflammation were seen.
A number of observations were drawn during this study: marked irritation of the treated area in the first week of application. Control animals receiving the base alone exhibited similar changes although less marked.
The skin changes were of 2 sorts:
- an incrustration resembling an extremly heavy dandruff, perhaps made up of skin plus crystals of PDMB
- a sloughing of skin in large areas.
The skin appeared tanned but points of attachment to the lower dermis were raw and sensitive when the sloughs was disattached. At the end of the month, advanced healing was present in all the rabbits even though daily treatment was continued. Low on the ventral side of the shaved area were the more extensive sloughs. This effect could be attributed to the accumulation of excess material which ran down the depilated area and was held by the fur at the site of the severe damage. The ears of the rabbits on the dorsal aspect lost hair and were irritated. Since the ears were frequently laid back on the areas that were treated, the contact might account for this effect. In some rabbits, certain areas exhibited a rapid regrowth of hairs creating a "patchy" effect. In these patches of longer hair, tree new skin was invariably raw and sensitive to a greater degree than elsewhere. It was possible that larger quantities of the lotion were held in such patches for a longer time.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion