Registration Dossier

Toxicological information

Repeated dose toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Not documented
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Documentation insufficient for assessment. No details of the method, evaluation, and results reported.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
The toxicology of glycidol and some glycidyl ethers
Author:
Hine, C.H. et al.
Year:
1956
Bibliographic source:
Arch. Ind. Health 14, 250-264 (1956)
Report Date:
1956

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Method: other: Based on Draize test - repeated application
GLP compliance:
no
Remarks:
study conducted prior to adoption of GLP
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Glycidol
- Molecular weight (if other than submission substance): 74.05
- Physical state: Liquid

Test animals

Species:
rabbit
Strain:
Californian
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Point Reyes, California or Gilroy Laboratory, California
- Age at study initiation: Not documented
- Weight at study initiation: Not documented
- Fasting period before study: Not documented
- Housing: Not documented
- Diet (e.g. ad libitum): Not documented
- Water (e.g. ad libitum): Not documented
- Acclimation period: Not documented

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not documented
- Humidity (%): Not documented
- Air changes (per hr): Not documented
- Photoperiod (hrs dark / hrs light): Not documented

IN-LIFE DATES: From: To: Not documented

Administration / exposure

Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on exposure:
Route of Administration: dermal
TEST SITE
- Area of exposure: Backs of the rabbits, treated area approximately 1 cm in diameter.
- % coverage: Not documented
- Type of wrap if used: Not documented
- Time intervals for shavings or clipplings: If it was necessary to clip regrowth of fur during the experiment, a period of at least 15 hours was allowed for healing of possible injury before further applications were made.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test area was wiped with soft laboratory tissues followed by tissues moistened with acetone.
- Time after start of exposure: one hour after application.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.2ml of undiluted test material.
- Concentration (if solution): applied as supplied
- Constant volume or concentration used: no data
- For solids, paste formed: not relevant

VEHICLE
Not relevant as substance was applied undiluted.

USE OF RESTRAINERS FOR PREVENTING INGESTION: no information provided
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No information provided
Duration of treatment / exposure:
1 h
Frequency of treatment:
once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
200 µl
Basis:

No. of animals per sex per dose:
6 male rabbits
Control animals:
no
Details on study design:
- Dose selection rationale: No information provided
- Rationale for animal assignment (if not random): No information provided
- Rationale for selecting satellite groups: No information provided
- Post-exposure recovery period in satellite groups: No information provided
- Section schedule rationale (if not random): No information provided
Positive control:
No information provided

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: No data

BODY WEIGHT: Yes
- Time schedule for examinations: No data

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: No data

CLINICAL CHEMISTRY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
Other examinations:
No additional information provided
Statistics:
No information provided

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Dermal irritation:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
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:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY
Three of the six animals died after the 7th application of the test substance. The erythema observed was greater than the oedema and it usually appeared earlier. There was a steady progression in the degree of irritation observed. Maximum irritation appeared as early as the fourth day - in some cases, application was discontinued after the fifth application because of maximum escharotic effect.

BODY WEIGHT AND WEIGHT GAIN
None of the animals gained weight and the weight of the animals that died decreased significantly prior to death.

FOOD CONSUMPTION
No information provided.

FOOD EFFICIENCY
No information provided.

WATER CONSUMPTION
No information provided.

OPHTHALMOSCOPIC EXAMINATION
No information provided.

HAEMATOLOGY
No information provided.

CLINICAL CHEMISTRY
No information provided.

URINALYSIS
No information provided.

NEUROBEHAVIOUR
No information provided.

ORGAN WEIGHTS
No information provided.

GROSS PATHOLOGY
Following necropsy, the skin treated with glycidol showed a more localised effect but deep penetration.

HISTOPATHOLOGY: NON-NEOPLASTIC
No information provided.

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
No information provided.

HISTORICAL CONTROL DATA (if applicable)
No information provided.

OTHER FINDINGS
Signs of systemic toxicity appeared 48 hours before death, and the surviving animals were below normal in appearance.

Effect levels

Dose descriptor:
LOAEL
Effect level:
200 other: µl/cm2
Sex:
male
Basis for effect level:
other: Only dose level tested

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

No weight gain, erythema appeared earlier than oedema and were greater, degree of irritation progressing, maximal on
day 4.
No further data reported.

Applicant's summary and conclusion

Conclusions:
In this dermal repeated dose toxicity study with glycidol in rabbits 3/6 animals died after the 7th application of 200 uL glycidol. Signs of systemic toxicity and skin irritation were observed. Based on the results of this study, the test substance should be classified as a STOT-RE2 toxicant with the Signal word "Warning" and the Hazard Statement H373: MAy cause damage to organs through prolonged or repeated exposure via the dermal exposure
Executive summary:

In a study conducted by Hine et al, (1956), the test substance, Glycidol, was examined for its ability to cause toxicity when applied to the shaved intact backs of 6 male Californian albino rabbits for 1 hour per day for successive days until eschar formation made it impossible for additional applications or systemic toxicity was observed. The test substance was applied at a dose of 200ul glycidol to an area approximately 1cm2 in diameter. Following treatment, 3 of the 6 animals died after the 7th application of the test substance. Signs of systemic toxicity were recorded 48 prior to death and the surviving animals did not have a normal appearance. The erythema observed was greater than the oedema and appeared earlier, with a steady progression in the degree of irritation observed with each successive application. Maximum irritation appeared on the 4th day of application in some animals. Necropsy reported a relatively localized effect with deep penetration. Based on the results of this study, the test substance should be classified as a STOT-RE2 toxicant with the Signal word "Warning" and the Hazard Statement H373: May cause damage to organs through prolonged or repeated exposure via the dermal exposure.