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Description of key information

Two acute oral studies have been conducted. One study reported the acute LD50 for males and females is reported as 2940 mg/kg bw. The other study reported the LD50 for female rats was calculated to be 2700 mg/kg bw; the LD50 for male rats was 3660 mg/kg bw. Both studies indicate that ETOX is a UN GHS Category 5 acute oral hazard. Neither study reported clinical signs or gross pathological findings that would indicate specific organ toxicity following single exposure.

 

Male rats were exposed to 635 ppm (measured concentration) ETOX vapour via whole body exposure. No mortality was reported. No toxicologically significant gross pathological findings were reported. The 7-hour LC50 is >635 ppm.

 

No deaths were reported following unabraded dermal exposure of 2 male and 2 female rabbits to 500 mg/kg bw active material presented as a 10% aqueous solution of ETOX. The dermal acute LD50 is >500 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reason / purpose for cross-reference:
reference to other study
Remarks:
Weight of evidence reference
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Temperature 20-26°C
Humidity: 45-75%
12h light / 12h dark
water: ad libitum

5 aminals/cage
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
- Concentration in vehicle:
5000 mg/kg bw - 10 mL/kg of a 50% solution
3160 mg/kg bw - 10 mL/kg of a 31.6% solution
2610 mg/kg bw - 10 mL/kg of a 26.1% solution
2150 mg/kg bw - 10 mL/kg of a 21.5% solution
Doses:
5000, 3160, 2610, 2150 mg/kg bw
No. of animals per sex per dose:
5 males/dose & 5 females/dose
Control animals:
no
Details on study design:
Cage weight monitored days 3, 4, 7, 13

Symptoms monitored: <15 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours and 5 hours, thereafter twice a week until end of study
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 940 mg/kg bw
Based on:
test mat.
Mortality:
At 5000 mg/kg bw, 100% of animals died
At 3160 mg/kg bw, 70% of animals died
At 2610 mg/kg bw, 20% of animals died
At 2150 mg/kg bw, 0% of animals died
Other findings:
General congestion hyperemia
Stomach: isolated bloody ulcerations, glandular stomach slight reddened
Intestine: blood-coloured contents, intestinal mucosa reddened
Liver: partly loam colored areas
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Five male and five female Sprague-Dawley rats were treated with a single oral gavage dose of ETOX at 5000, 3160, 2610, and 2150 mg/kg bw and observed for 14 days. Clinical signs were observed during the 14 day observation period and macroscope examination of organs occurred at the end of the study. There were symptoms of general congestion hyperemia, isolated bloody ulcerations in the stomach, the glandular stomach was slight reddened, the intestinal mucosa were reddened and the liver has partly loam coloured areas. The acute LD50 for males and females is reported as 2940 mg/kg bw.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reason / purpose for cross-reference:
reference to other study
Remarks:
Weight of evidence reference
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Route of administration:
oral: gavage
Vehicle:
water
Doses:
5 rats / sex / dose: 1000, 2000, 2520, 3160, 3980 mg/kg bw.
5 male rats / dose: 3610, 3400, 3680, 3980 mg/kg bw
Details on study design:
Five rats per sex per dosage level were given 1000, 2000, 2520, 3160, or 3980 mg/kg of the material as a 20% solution in water by single-dose gavage. Then 5 male rats per level were given 3160, 3400, 3680, or 3980 mq/kq in the same manner. Food was withheld from the rats for 16-18 hours before treatment. The animals were weighed just prior to treatment, the day following treatment, and weekly thereafter for the two week post-treatment observation period. The animals were observed periodically for signs of toxicity. Survivors were submitted for a gross pathological examination two weeks post-treatment.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
2 700 mg/kg bw
Based on:
test mat.
95% CL:
> 2 500 - < 3 230
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
3 660 mg/kg bw
Based on:
test mat.
95% CL:
> 3 350 - < 4 340

Tremors and lethargy were noted the day of treatment and the day following in groups dosed at 2000 mg/kg bw and higher; convulsions were observed those 2 days in groups dosed at 2520 mg/kg bw and higher. Dark red nasal secretions and diuresis were apparent the day following treatment on males dosed at 2520 mg/kg bw and higher; imbalance or lack of co-ordination was apparent the day of treatment on male rats dosed at 2520 mg/kg bw and at higher doses on the next day as well.

 

Most of the survivors exhibited no treatment-related lesions or conditions at the gross pathological examination. The non-glandular portion of the stomach appeared to be slightly thickened on 1 female and 2 males dosed at 2000 mg/kg bw. The kidneys of 1 male dosed at 3160 mg/kg bw appeared pale, and of another male from the same group, slightly swollen. The mucosal surface of the stomach of 1 male dosed at 3400 mg/kg contained a nodule about 4 mm in diameter.

 

In general, the survivors appeared healthy at the 2-week weighing. The animals dosed at the higher levels gained weight, but not as much as the animals dosed at lower levels.

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Five male and five female Sprague-Dawley rats were treated with a single oral gavage dose of ETOX and observed for 14 days. Tremors and lethargy were noted the day of treatment and the day following in groups dosed at 2000 mg/kg bw and higher; convulsions were observed those 2 days in groups dosed at 2520 mg/kg bw and higher. Dark red nasal secretions and diuresis were apparent the day following treatment on males dosed at 2520 mg/kg bw and higher; imbalance or lack of co-ordination was apparent the day of treatment on male rats dosed at 2520 mg/kg bw and at higher doses on the next day as well.

Most of the survivors exhibited no treatment-related lesions or conditions at the gross pathological examination. The non-glandular portion of the stomach appeared to be slightly thickened on 1 female and 2 males dosed at 2000 mg/kg bw. The kidneys of 1 male dosed at 3160 mg/kg bw appeared pale, and of another male from the same group, slightly swollen. The mucosal surface of the stomach of 1 male dosed at 3400 mg/kg contained a nodule about 4 mm in diameter.

In general, the survivors appeared healthy at the 2-week weighing. The animals dosed at the higher levels gained weight, but not as much as the animals dosed at lower levels.
The LD50 for female rats was calculated to be 2700 mg/kg bw; the LD50 for male rats was 3660 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 700 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reason / purpose for cross-reference:
reference to other study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
fixed concentration procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Details on inhalation exposure:
- Exposure chamber volume: 19 liter glass chamber
- System of generating particulates/aerosols: The ETOX atmosphere was generated by bubbling air through liquid ETOX at room temperature (~23°C) at a rate of 0. 5 liters per minute for 7 hours, while filtered air at a rate of 0.5 liters/minute was mixed with the vapor airstream prior to entry into the exposure chamber.

Analytical Verification:
The analytical concentration of ETOX in the exposure· chamber as determined by infrared spectrophotometry using a Miran I infrared spectrophotometer equipped with a variable pathlength gas cell. The wavelength used for the analysis was 9.9µ. Chamber air analysis was performed by attaching a Saran gas sampling bag to the exhaust port of the chamber, collecting 8 liters of the exhausted chamber atmosphere, and diluting it with 32 liters of filtered air to acquire sufficient volume to pump through the gas cell of the infrared spectrophotometer for analysis. Standards were made using 100 liter Saran gas sampling bags connected to a glass U-tube for evaporation of ETOX prior to entry into the bag. The U-tube was gently heated with an air gun to improve evaporation of the test material. The nominal concentration of ETOX vapor in the chamber was calculated from the weight of material used and the total airflow through the chamber.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
7 h
Concentrations:
Nominal 5,960 ppm (20.5 mg/l)
No. of animals per sex per dose:
5 control animals
6 treatment animals
Control animals:
yes
Details on study design:
During and after exposure the rats were observed for signs of toxicity, such as eye and nasal irritation and respiratory distress. Body weights were taken prior to exposure and 3 times a week for 2 weeks after exposure. At the end of this period gross pathologic examinations were performed on all rats.
Sex:
male
Dose descriptor:
LC50
Effect level:
> 20.5 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
7 h
Remarks on result:
other: 5068 ppm
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
> 635 ppm
Based on:
test mat.
95% CL:
> 578 - < 692
Exp. duration:
7 h
Remarks on result:
other: time weighted analytical concentration
Mortality:
No mortality
Clinical signs:
other: Throughout most of the 7 hour exposure to ETOX the rats' extremities (ears, paws, scrotal sacs, and tails) were pinker than those of the control rats, their respiration was labored, and their reaction to sound was diminished (anesthetic symptom). Upon rem
Body weight:
After an initial body weight decrease, the ETOX exposed rats gained weight in a manner comparable to the controls.
Gross pathology:
Upon gross pathologic examination 1 of 5 control rats and 5 of 6 ETOX exposed rats were described as having pale kidneys but were otherwise normal.

The control chamber atmosphere was analyzed by infrared spectroscopy to determine whether ammonia from the rats' urine would interfere with the infrared analysis for ETOX. No significant interference was found.

The nominal concentration of ETOX in the exposure chamber was calculated as 5,068 ppm (20.5 mg/L), while the time weighted analytical concentration was found to be 635±57 ppm. This marked difference was attributed to the adherence of ETOX to the walls of the chamber and to its affinity for the water produced by condensation from expired air and from urination in the small 19 liter exposure chamber.

Interpretation of results:
GHS criteria not met
Conclusions:
Male rats were exposed to 635 ppm (measured concentration) ETOX vapour via whole body exposure. No mortality was reported. No toxicologically significant gross pathological findings were reported. The 7-hour LC50 is >635 ppm.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
The animals were placed in individual holding cages with free access to food and water.
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
Acute percutaneous absorption toxicity was evaluated by application of 500 mg/kg of the active material as a 10% aqueous solution to the intact skin of 2 male and 2 female rabbits and 500 or 252 mg/kg to abraded skin on similar groups of rabbits. Twenty-four hours prior to application, the entire trunk of each rabbit was clipped free of hair with electric clippers. The material was applied under a heavy gauge plastic cuff which was held in place by rubber bands. The plastic cuff was covered with a cloth bandage taped securely to the marginal hair. After 24 hours the cuffs were removed, and the skin was washed with soap and water, rinsed thoroughly, and dried with a cloth towel.
Doses:
500 mg/kg (as a 10% aqueous solution) to intact skin
500 or 252 mg/kg to abraded skin
No. of animals per sex per dose:
2 males and 2 females per dose
Control animals:
no
Details on study design:
The topical response at the site of application was evaluated after removal of the plastic cuff. The animals were observed frequently during exposure and for the following two weeks for signs of toxicity. Body weights were recorded before and after the 24-hour exposure period and at 1 and 2 weeks post-treatment, or until pre-treatment weight was regained.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 500 mg/kg bw
Based on:
test mat.
Mortality:
The 2 female rabbits from the 500 mg/kg group with abraded skin died 17 and 18 days after treatment.
Clinical signs:
The animals with intact skin exhibited slight to moderate redness and slight to severe swelling when the cuffs were removed; the animals with abraded skin, exhibited very slight redness and swelling (252 mg/kg group); and slight to severe redness with slight to moderate swelling (500 mq/kg group). One male and one female from the abraded 500 mg/kg group exhibited slight transient diarrhea, then the other female developed severe diarrhea prior to death.
Body weight:
All of the animals from the abraded skin group gained weight during the first week following treatment, then lost weight (0.12 to 0.47 kg) during the second week, and the 2 male rabbits required 2 more weeks to equal pre-treatment weight. The animals from the other groups regained pre-treatment weight in 1 - 2 weeks with all animals showing a weight gain during the second week.
Interpretation of results:
study cannot be used for classification
Conclusions:
No deaths were reported following unabraded dermal exposure of 2 male and 2 female rabbits to 500 mg/kg bw active material presented as a 10% aqueous solution of ETOX.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for classification or non-classification

Acute oral: The measured acute oral toxicity of the ETOX is greater than 2000 mg/kg bw. Therefore, according to EC 1272/2008 as amended, the test substance does not meet the criteria for acute toxicity (oral) classification.

 

Acute Inhalation: The measured acute inhalation toxicity of the ETOX is (7h) LC50>635 ppm. Therefore, according to EC 1272/2008 as amended, the test substance does not meet the criteria for acute toxicity (inhalation) classification.

 

Acute Dermal: The acute dermal study investigated the acute toxicity of ETOX up to a maximum concentration of 500 mg/kg bw active material; no deaths were reported in the unabraded study group. However, this information is insufficient for the purposes of classification. As ETOX is CLP classified as Skin Corrosive Category 1B, no further investigation recommended.

STOT SE: The clinical symptoms and gross pathological findings do not indicate target organ toxicity following single exposure. Therefore, according to EC 1272/2008, as amended, the test substance does not meet the criteria for STOT SE classification.