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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Not documented
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Significant methodological deficiences. Exposure to one dose only.
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)

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Rats were exposed to the test substance at one concentration for 50 days via inhalation route.
GLP compliance:
not specified
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:
rat
Strain:
Long-Evans
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gilroy Laboratories, California.
- Age at study initiation: Not documented
- Weight at study initiation: Not documented
- Fasting period before study: Not documented
- Housing: Housed 2 to a cage
- Diet (e.g. ad libitum): Special green powdered feed which afforded optimum nutritional conditions.
- 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

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
not specified
Remarks on MMAD:
MMAD / GSD: No information provided
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Exposure chambers of 200 litre capacity
- Method of holding animals in test chamber: Not documented
- Source and rate of air: The constant metering device delivered the substance in measured amounts to the evaporator, where they were vapourized in the air entering the chamber. The air in the chamber was allowed to equilibrate to a theoretical 95 to 99% of the desired concentration before the animals were introduced.
- Method of conditioning air: Not documented
- System of generating particulates/aerosols: Not documented
- Temperature, humidity, pressure in air chamber: Not documented
- Air flow rate: 11.7 to 22 L/min.
- Air change rate: 3.5 to 6.6 air changes per hour.
- Method of particle size determination: Not documented
- Treatment of exhaust air: Not documented

TEST ATMOSPHERE
- Brief description of analytical method used: Vapour concentrations were monitored by frequent analysis of air drawn from a sampling port and absorbed in a magnesium chloride and hydrochloric acid solution.
- Samples taken from breathing zone: no data

Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Vapour concentrations were monitored by frequent analysis of air drawn from a sampling port and absorbed in a magnesium chloride and hydrochloric acid solution.
Duration of treatment / exposure:
10 weeks
Frequency of treatment:
5 days/week, 7 h/day
Doses / concentrations
Remarks:
Doses / Concentrations:
400 ppm
Basis:

No. of animals per sex per dose:
No information provided
Control animals:
yes
Details on study design:
Post-exposure period: no data
Control animals received untreated air.
Positive control:
No information provided

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

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: Yes
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked: Haemoglobin

CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes - lungs, Iivers, and kidneys of all animals were freed of connective tissue and excess moisture and weighed for determination of organ/body weight ratios.
HISTOPATHOLOGY: Yes - brain, thyroid, thymus, heart, stomach, intestine, pancreas, adrenal, testis, and bladder as well as sections from the tissues taken in gross pathological examinations.
Other examinations:
Organ/body weight ratios, percentage weight gain and haemoglobin concentrations were examined.
Statistics:
Organ/body weight ratios, percentage weight gain and haemoglobin concentrations were compared with those of the controls using the Student t-test.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not specified
Details on results:
No lethality, slight retardation of weight gain, necropsy revealed no gross histopathological lesions, slight decrease of peritoneal fat, no effect on organ weights, slightly increased hemoglobin concentration.

Effect levels

Dose descriptor:
NOAEC
Effect level:
400 ppm
Based on:
not specified
Sex:
male/female
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 lethality, slight retardation of weight gain, necropsy revealed no gross histopathological lesions, slight decrease
of peritoneal fat, no effect on organ weights, slightly increased hemoglobin concentration.


Applicant's summary and conclusion

Conclusions:
In this 50-day inhalation toxicity study with glycidol in rats no mortality, no effect on organ weights and no gross histopathological lesions occured. A slight decrease of peritoneal fat, slightly increased hemoglobin concentration and slight retardation of weight gain were observed.
Executive summary:

In a study conducted in 1956 by Hines et al, the test substance was examined for its ability to cause toxicity when administered to male Long-Evans for a testing period of 50 days. The test animals were exposed to the test substance 7 hours per day, 5 days per week for 50 days via the inhalation route. The test substance was admininstered at a concentration of 400ppm. The test animals were observed during exposure and gross and histopathological examinations were conducted following exposure. Following exposure, no mortality, no effect on organ weights and no gross histopathological lesions occured. A slight decrease of peritoneal fat, slightly increased hemoglobin concentration and slight retardation of weight gain were observed.