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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September to October 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report date:
1979

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Method: other: Sprague-Dawley rats, 10 male and 10 female, application with stomach tube; LD50 was calculated by the method of Litchfield and Wilcoxon.
GLP compliance:
no
Remarks:
study conducted prior to adoption of GLP
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2,3-epoxypropan-1-ol
EC Number:
209-128-3
EC Name:
2,3-epoxypropan-1-ol
Cas Number:
556-52-5
Molecular formula:
C3H6O2
IUPAC Name:
oxiran-2-ylmethanol
Details on test material:
Test substance: Glycid
Physical State: Liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: S.IVONAS Postfach 7, D-7964 Kissleg/Allgau
- Age at study initiation: 52 days for males and 70 days for females
- Weight at study initiation: 175-180 g
- Fasting period before study: 16 hours
- Housing: Animals were housed individually in Makrolon cages (Type III).
- Diet (e.g. ad libitum): RF-M 771 ad libitum, except for 16 hours prior to administration of the test substance.
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: Not documented

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 0.5°C
- Humidity (%): 55 ± 5%
- Air changes (per hr): Not documented
- Photoperiod (hrs dark / hrs light): Not documented

IN-LIFE DATES: From: September To: October 1978

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Test substance was administered undiluted.

MAXIMUM DOSE VOLUME APPLIED:
1.0 ml/kg.

DOSAGE PREPARATION (if unusual): Not documented

Doses:
0.147, 0.215, 0.316, 0.464, 0.681, 1.0 mL/kg
No. of animals per sex per dose:
10 per sex per group with the exception of the highest dose level tested which only used 10 females.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days up to 4 weeks.
- Frequency of observations and weighing: Not documented
- Necropsy of survivors performed: yes
- Other examinations performed: Not documented
Statistics:
LITCHFIELD and WILCOXON where appropriate

Results and discussion

Preliminary study:
Not relevant
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
463.8 mg/kg bw
Mortality:
Number of decedents at 24 hours after dosing and total number of decedents at scheduled termination after 14 days.
0.316 ml/kg dose group: 2 females after 24 hours and 2 females and 1 male after 14 days.
0.464 ml/kg dose group: 5 males and 7 females after 24 hours and 5 males and 7 females 14 days.
0.681 ml/kg dose group: 10 males and 8 females after 24 hours and 10 males and 9 females after 14 days.
1.0 ml/kg dose group: All female test animals died.
Clinical signs:
sedation, ataxia, dyspnoea, muscular hypotonia
Body weight:
Not documented
Gross pathology:
In the 0.147 and 0.215 dose groups, there was no evidence of abnormal reactions following administration. In the 0.215ml/kg dose group, 1 animal had a decreased lung lobe, however, there were no pathological findings.
In the 0.316 ml/kg dose group, pale ulcers were observed on the stomach wall, as well as restricted parenchyma on the animals that died. In the surviving animals, renal abnormalities were observed.
In the 0.464 ml/kg dose group, the animals that died had pale liver and kidneys , with some showing enlarged ulceration of the stomach wall and kidneys. In the survivng animals, pale kidneys were observed, usually without specific pathological findings.
In the 0.681 ml/kg dose group, the animals that died had pale liver and kidneys , with some showing enlarged ulceration of the stomach wall (up to 0.5mm). Surviving female animals did not show any specific pathological findings.
In the 1.0 ml/kg dose group, the liver was stained pale and had a gritty structure. The stomach wall also showed ulceration.
Other findings:
reduced food consumption, cirrhotic liver

Any other information on results incl. tables

No additional information

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the conditions of this study, an acute oral toxicity LD50 value of 464 mg/kg bw was determined. Based on this result, the test susbtance should be considered to be a category 4 toxicant, with the hazard statement H302: Harmful if swallowed and the signal word Warning associated with it, according to Regulation EC No. 1272/2008. According to Directive 67/548/EEC, the test substance should be classified as Harmful (Xn) and have the risk phrase R22: Harmful if swallowed associated with it.
Executive summary:

In a study conducted in 1979, the test substance, Glycid, was investigated for its ability to cause toxicity when administered via the oral route to male and female Sprague-Dawley rats. The test substance was administered via oral gavage at concentrations of 0.147, 0.215, 0.316, 0.681 and 1.0ml/kg, with only females receiving the highest dose level. The test animals were observed for 14 days up to 4 weeks.

Mortalities were observed in each test group, except the 2 lowest concentrations. In the 0.316 ml/kg dose group 2 females died after 24 hours and 2 females and 1 male died after 14 days. In the 0.464 ml/kg dose group 5 males and 7 females died after 24 hours and 5 males and 7 females died after 14 days. In the 0.681 ml/kg dose group, 10 males and 8 females died after 24 hours and 10 males and 9 females died after 14 days. In the 1.0 ml/kg dose group, all female test animals died. Other observations included sedation, ataxia and a prone position, as well as reduced food consumption. Macropscopic findings included ulceration of the stomach wall and effects on the liver and kidneys.

Under the conditions of this study, an acute oral toxicity LD50 value of 464 mg/kg bw was determined. Based on this result, the test susbtance should be considered to be a category 4 toxicant, with the hazard statement H302: Harmful if swallowed and the signal word Warning associated with it, according to Regulation EC No. 1272/2008. According to Directive 67/548/EEC, the test substance should be classified as Harmful (Xn) and have the risk phrase R22: Harmful if swallowed associated with it.