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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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented study report which meets basic scientific principles, pre-GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1961
Report Date:
1961

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Test material was applied by skin contact once daily for a total of 10 applications with a one-day rest period between the first and second applications, and a two day rest period between the third and fourth and eight and ninth applications.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MRD-59-12
- Physical state: liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.6-2.5 kg
- Acclimation period: 5 d

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on exposure:
TEST SITE
- Area of exposure: Back and/or abdominal skin
- % coverage: 10% for 0.5 ml/kg dose, 40% for the 2.5 ml/kg dose
- Type of wrap if used: Gauze and plastic sleeve
- Time intervals for shavings or clippings: Frequent intervals


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 or 2.5 ml/kg
- Concentration (if solution): 100%
- Constant volume or concentration used: no

Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
18-24 hours estimated exposure time.
Frequency of treatment:
Test material was applied by skin contact once daily for a total of 10 applications with a one-day rest period between the first and second applications, and a two day rest period between the third and fourth and eight and ninth applications.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.5
Basis:
other: ml/kg/application
Remarks:
Doses / Concentrations:
2.5
Basis:
other: ml/kg/application
No. of animals per sex per dose:
2 Male, 2 Female
Details on study design:
- Undiluted control and test material were applied to intact skin of the animals once daily for a total of 10 applications with a 1 day rest period between the first and second applications, and a 2 day rest period between the third and fourth and eighth and ninth applications.
Positive control:
Isopropyl alcohol

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS:
- Time schedule: Daily


DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: daily


HAEMATOLOGY: Yes
- Time schedule for collection of blood: Initially and 24 hours following the final application
- Parameters checked: total erythrocyte count, total and differential leukocyte counts, hematocrit determination


URINALYSIS: Yes
- Time schedule for collection of urine: Initially and 24 hours following the final application
- Parameters checked: Complete urine analysis.

Sacrifice and pathology:
GROSS PATHOLOGY:
- 48 hours following the tenth application the animals were sacrificed by intravenous air embolism.
- From each animal, samples of brain, thyroid, lung, heart, liver, kidney, adrenals, skin, and bone marrow.
Statistics:
No data analyzed

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
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:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
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
Details on results:
CLINICAL SIGNS AND MORTALITY
- No mortality from exposure

BODY WEIGHT AND WEIGHT GAIN
- Final weight of each animal was increased over the initial value.

HAEMATOLOGY
- General improvement in hematocrit and total erythrocyte during the course of the study
- Slight shift in the differential count noted in the high dose group
- Terminal increase in segmented neutrophils count in the high dose group

URINALYSIS
- Unremarkable

GROSS PATHOLOGY
- Unremarkable

Effect levels

open allclose all
Dose descriptor:
other: skin irritation
Effect level:
>= 0.5 other: ml/kg
Sex:
male/female
Basis for effect level:
other: Moderate erythema, slight or moderate edema, and slight to marked atonia and desquamation.
Dose descriptor:
NOAEL
Effect level:
> 2.5 other: ml/kg
Sex:
male/female
Basis for effect level:
other: No adverse systemic effects reported.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Repeated applications of isooctanol at 0.5 or 2.5 ml/kg of body weight produced moderate or marked degree of dermal irritation. The irritation was characterized by slight or moderate erythema, slight or moderate edema, and slight to marked atonia and desquamation.
Executive summary:

In this study, male and female rabbits were subjected to a repeated dose of either 0.5 or 2.5 ml/kg body weight isooctanol. Undiluted control and test material were applied to intact skin of the animals once daily for a total of 10 applications with a 1 day rest period between the first and second applications, and a 2 day rest period between the third and fourth and eighth and ninth applications. Repeated applications of isooctanol produced moderate or marked degree of dermal irritation. The irritation was characterized by slight or moderate erythema, slight or moderate edema, and slight to marked atonia and desquamation. In addition, two of the low level animals showed slight necrosis, and all of the high level animals showed fissuring and a coriaceous condition of the skin. No adverse systemic effects were noted even at the highest dose of 2.5 ml/kg.