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Administrative data

Description of key information

The acute oral toxicity of the test substance, 2,3-epoxypropyl o-tolyl ether, was accessed in three independent rat studies.  The test substance was evaluated in an O.E.C.D. test guideline no. 403 rat four hour Acute Inhalation study.  The acute aerosol inhalation toxicity of the tst substance was also evaluated in a rat, nose-only four hour study.  Acute dermal toxicity was evaluated in two independent rat 24 hr exposure studies and a rabbit 24 hour study..    

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was not conducted according to any established test guideline or the GLP regulations. Furthermore, study detail is limited, rat strain is unknown and test substance is ill defined.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Inhalation toxicity was tested accordinq to the method of Sachese et a1. (1973, 1976).
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Tif RAIF (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
The rat strain was proprietary to Ciba-Geigy. Before and after the inhalation the animals were kept at a room tanperatire of 22 ± 1° C, at a relative humidity of 55 ± 5%I and on a 10 hours light cycle day. They received ad libitüm rat food and water. Prior to treatment they were adapted 1aboratory conditions for a minimum of 4 days. The initial body weights ranged from 190 to 235 grams. The animals maintained in Maorolon cages, type 4, (10 aninals to a cage).
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
The inhalation chamber aerosols were generated by injecting the liquid test substance at a rate of 6, 12,310 and 60 mL/hr into a clean air stream which was discharged into the exposure chamber through a spray hozzle under a pressure of 2 atm. at a rate of 10 mL/mim. The concentration and the particle size distribution of the aerosol in the vicinity of the animals was monitored at 1 hour intervals throughout the aerosol exposure The concentration was determined gravimetrically by sampling the test atmosphere.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
ca. 4 h
Concentrations:
Approximately 999, 2750, 3970 and 8140 mg/m3 (nominal).
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
The rats were exposed nose-only to the aeresols of the test substance for four hours. After a 4 hour inhalation the rats were returnea to their cages.Physital condition and incidence of death were monitored throughout an observation period of 14 days.
Statistics:
No data
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 6 090 mg/m³ air (nominal)
Based on:
test mat.
95% CL:
ca. 4 795 - ca. 8 510
Exp. duration:
4 h
Mortality:
15/20 at 8140 mg/m3 and 4/20 at 3970 mg/m3. At the high concentration 9/20 died within 0-4 hr and 14/20 had died within 48 hr. At 3970 mg/m3 the four animals had died by 48 hr.
Clinical signs:
other: Within 2 to 4 hours of starting the exposure period the rats in all concentratiohs showed dyspnoea, exophthalmos, ventral or curved position. In addition the rats in the highest concentration showed ataxia.
Body weight:
No data
Gross pathology:
Animals dying on-study had small isolated hemorrhages in the lungs. No gross pathology was observed in the animals surving to study termination.
Interpretation of results:
relatively harmless
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
With an aerosol inhalation LC50 of 6090 mg/m3 in the rat the test substance is relativel non-toxic by inhalation.
Executive summary:

The test substance was accessed for acute aerosol inhalation toxicity in a four hour nose-only exposure study with rats. The aerosol inhalation LC50 of 6090 mg/m3 in the rat suggests that the test substance is relativel non-toxic by aerosol inhalation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
6 090 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted similar the O.E.C.D. test guideline 402 with limited evidence of GLP compliance.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
GLP compliance:
no
Remarks:
Documentation of GLP compliance is limited.
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
The rabbits acquired from Ray Nichols Rabbitry, Lumberton, Texas, were used in the study. The animals were caged individually with ad libitum food and water. The rabbits were held for an acclimation period of 22 days. The animal room was maintained with a temperature range of 18.9—20.0°C and relative humidity range 35—87%. A light cycle of 12 hours on (6 a.m.- 6 p.m.) and 12 hours off was maintained throughout the study.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The day before exposure the rabbits to placed on-study were clipped of all hair over the back/trunk region using an electric clipper. On the day of treatment the required amount of test material was applied undiluted to the rabbit’s back under a 4 x 4 inch surgical gauze patch secured in place with tape. and covered with impervious/occlusive plastic wrap (Saran Wrap) and an overwrap of an elastic Ace bandage to immobilize the patch. Following a 24—hour exposure period, the dressings were removed and any remaining material removed with a moist towel.
Duration of exposure:
24 hr
Doses:
Approximately 2200 mg/Kg of body weight
No. of animals per sex per dose:
8
Control animals:
yes
Details on study design:
Following experimental initiation observations for mortalities and clinical signs of toxicity were made at 1, 2, 4, and 6 hours following application, at 24 hours and twice daily (a.m. and p.m.) thereafter until termination of the study on day 14. In addition, each exposure site was scored for degree of irritation according to the method of Draize following the removal of the occlusive covering and prior to termination on day 14. Body weights were determined on days —1, 0, 7 and 14. All animals dying during the study were necropsied. Survivors were necropsied on day 14, following euthanasia.
Statistics:
The independent T-test was used to determine significance for body weight differences. The 95% confidence limits of the observed incidence of mortalities was obtained from CRC Handbook of Tables for Probability and Statistics (1979).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 200 mg/kg bw
Based on:
test mat.
Mortality:
5/16
Clinical signs:
No clinical signs of toxicity occurred over the first experimental day. Prominent clinical signs of toxicity observed after the occlusive wrappings were removed included hypoactivity, hypopnea, cyanosis, hypothermia and incoordination of the rear limbs.
Body weight:
Exposed animals showed little/or no body weight gain over the 14 day observation period.
Gross pathology:
No treatment related gross pathology effects, other than dermal site findings were observed.
Other findings:
Severe edema and erythema was evident at 24 hours at all application sites. By 14 days the application sites were necrotic.
Interpretation of results:
sligthly toxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The test substance did induce some acute dermal toxicity in the rabbits with 5/16 moralities occuring at a dose level of approximately 2200 mgKg of body weight. Evidence of severe skin irritation/corrosion was observed following the 24 hr occlusive exposure to the test substance.
Executive summary:

The test substance, 2,3 -epoxypropyl o-tolyl ether was accessed for acute dermal toxicity in the rabbit by a 24 hr occlusive dermal exposure.The test substance did induce some acute dermal toxicity in the rabbits with 5/16 moralities occuring at a dose level of approximately 2200 mgKg of body weight. Therefore the rabbit acute dermal LD50 is > 2200 mg/Kg. Evidence of severe skin irritation/corrosion was observed following the 24 hr occlusive exposure to the test substance.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
Based on the outcome of two reliable acute dermal toxicity studies the LD50 is > than 2000 mg/Kg of body weight.

Additional information

Based on a weight-of-evidence approach, the rat acute oral toxicity of the test substance, 2,3 -epoxypropyl o-tolyl ether is > 2000 mg/Kg of body weight. The test substance was non-toxic to rats when exposed to the maxium achievable vapor concentration of 6.1 ppm for four hours. Therefore, the LC50 value for the test substance is > 6.1 ppm. The test substance was accessed for acute aerosol inhalation toxicity in a four hour nose-only exposure study with rats. The aerosol inhalation LC50 of 6090 mg/m3 in the rat suggests that the test substance is relatively non-toxic by aerosol inhalation. The rat acute dermal LD50 was > 2000 mg/Kg of body weight in two independent 24 hr occlusive exposure studies. The rabbit acute dermal toxicity study also had a LD50 of > 2000 mg/Kg of body weight. However, there were 5/16 mortalties at approximately 2200 mg/Kg and substantial evidence of skin corosion/irritation in this rabbit study.


Justification for selection of acute toxicity – oral endpoint
Weight-of-Evidence demonstrates that the acute oral LD50 value is > 2000 mg/Kg of body weight.

Justification for selection of acute toxicity – inhalation endpoint
Adverse clinical signs and mortality were observed in the study.

Justification for selection of acute toxicity – dermal endpoint
Adverse clinical signs and mortality in this study.

Justification for classification or non-classification

Based on the available study data, Classification and Labeling for acute toxicity is not required.