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Administrative data

Description of key information

The acute oral and dermal toxicity of 2-allyloxymethyl-2-ethylpropanediol is low. The oral LD50 of the substance in the rat is 4930 mg/kg bw. The dermal LD50 of the substance in the rabbit is > 15800 mg/kg bw. A waiver is proposed in accordance with Column 2 of Annex VIII of the REACH Regulation for acute inhalation toxicity on the basis that acute toxicity data are available for the oral and dermal routes.  Inhalation is not predicted to be a significant route of exposure based on the physicochemical properties of the substance.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April - May 1961
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No indication of guideline followed or GLP compliance.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Rats were administered a single dose of test material via stomach intubation and were observed for 14 days to determine the toxicity of the test substance when administered orally.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Albino
Sex:
male
Details on test animals and environmental conditions:
Five male albino rats weer used. The rats were non-fasted.
Route of administration:
oral: gavage
Vehicle:
other: mazola
Details on oral exposure:
The chemical was diluted with mazola and the concentration of the aliquots to be used for dosing the various concentration levels was adjusted so that no less than on milliliter or more than 10 milliliters was given to each animal.
Doses:
The rats were administered at four consecutive dosage levels differing by a factor of 2, specifically: 2, 3.98, 7.95 and 15.8 g/kg.
No. of animals per sex per dose:
5 male rats per dose.
Control animals:
no
Details on study design:
Doses were administered by stomach intubation to groups of five male albino rats who were non-fasted. Each rat received between 1 and 10 ml of test material. The rats were observed for 14 days at which time mortality due to chemcial exposure was considered complete. All fatalities were subjected to autopsies to include extraneous causes of death. Survivors were sacrificed and examined for the existence of gross lesions.
Statistics:
he single oral dose LD50 based on mortality during the 14-day observation period was estimated by Thompson's method of moving averages employin tables of Weil.
Preliminary study:
Not applicable.
Sex:
male
Dose descriptor:
LD50
Effect level:
4.93 other: g/kg
Based on:
test mat.
95% CL:
3.73 - 5.16
Mortality:
1 rat died 1 day after dosing at the 3.98 g/kg dose level.
All 5 rats died at the 7.95 g/kg dose level, with 4 rats dead 4 hours after dosing and 1 rat dead 1 day after dosing.
All 5 rats died less than 1 hour after dosing at the 15.8 g/kg dose level.
Clinical signs:
At the higher concentrations tested, trimethylolpropane monoallyl ether resulted in a slight narcotic effect on rats.
Body weight:
For the surviving rats in the 2.00 and 3.98 g/kg dose groups, an increase in body weight was recorded.
Gross pathology:
The survivors of the 14-day observation period showed no gross lesions upon examinaiton following sacrifice.
Other findings:
The growth of the surviving rats was normal and they were in good condition.

The Acute Oral Toxicity for Rats of Trimethylolpropane Monoallyl Ether.

Average Weight (kg)

 

 

Dosage g/kg

Initial

Change 14 days

Number Died / Number Dosed

Days after dosing on which death occurred.

2.00

115

+66

0/5

-

3.98

124

+80

1/5

1 (1)

7.95

128

-

5/5

4 hrs (4), 1 (1)

15.8

120

-

5/5

1hr (3), 2 (1), 3 (1)

Interpretation of results:
sligthly toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of trimethylolpropane monoallyl ether was determined to be 4.93 g/kg, when tested on male rats.
Executive summary:

The acute oral toxicity of Trimethylolpropane monoallyl ether was determined in male albino rats. Groups of five male albino rats were administered a single dose of Trimethylolpropane monoallyl ether at dose levels of 2, 3.98, 7.95 and 15.8 g/kg via stomach intubation. The rats were observed for 14 days and an oral LD50 based on mortality was determined to be 4.93 g/kg. 1 mortality was observed in the 3.98 g/kg dose group the day after dosing. In the 7.95 and 15.8 g/kg dose groups, all 5 rats in each group died within 1 day of dosing. All surviving rats had an increase in body weight followig the 14 day observation period.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
4 930 mg/kg bw
Quality of whole database:
Klimisch score = 2. The single study available was a range-finding investigation conducted prior to acceptance of GLP and test guidelines but the data are acceptable.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

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
Study period:
April - May 1961
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No indication of guideline followed of GLP compliance.
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test material was applied to a clipped area on rabbits for a 24 hour exposure period and was observed for 14 days to determine the toxicity of the test substance when applied dermally.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
other:
Sex:
male
Details on test animals and environmental conditions:
Groups of 4 male albino rabbits were used. The rabbits weighed 2 - 3 kgs.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The fur of the rabbits was clipped over the entire trunk, which equated to approximately 10% of the body surface and this area was coverd by an impervious plastic film. The calculated dose of the undiluted chemical was introduced through a cathether once the plastic cover was in place. The maximum dose applied to the rabbits was 20 milliliters/kg bw.
Following application of the test material, the rabbits were confined in stocks for 24 hours, after which the cover and the chemical were removed and the skin examined for gross changes.
Duration of exposure:
24 hours.
Doses:
3.95, 7.5 and 15.8 g/kg.
No. of animals per sex per dose:
4 male rabbits per dose group.
Control animals:
not specified
Details on study design:
Male albino rabbits (4 per dose group) were exposed to Trimethylolpropane Monoallyl Ether via dermal penetration. The degree of penetration through the intact skin was estimated employing the one-day cuff method used by Draize and associates as modified by Smyth and associates. The fur was clipped from the entire trunk of each animal and the test material was held in contact with the skin for 24 hours by an occlusive dressing. Following this exposure period, the dressing and test material were removed and the skin examined for any signs of gross changes. Mortality due to the effect of the chemical was considered complete after 14 days. All fatalities were subjected to autopsies to exclude extraneous causes of death while some survivors were sacrificed and examined for the existence of gross lesions.
Statistics:
No information provided.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 15.8 other: g/kg.
Based on:
test mat.
Mortality:
There were no mortalities observed in this study.
Clinical signs:
When dosed at 15.8 g/kg, necrosis of the skin was observed.
Body weight:
All animals
Gross pathology:
No information provided.
Other findings:
No additional information.

Skin penetration Toxicity for Rabbits of Trimethylolpropane Monoallyl Ether.

Average Weight (kg)

 

 

Dosage g/kg

Initial

Change 14 days

Number Died / Number Dosed

Days after dosing on which death occurred.

3.98

2.26

+0.33

0/4

-

7.95

2.04

+0.51

0/4

-

15.8

2.04

+0.07

0/4

-

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of Trimethylolpropane Monoallyl Ether by skin penetration for male albino rabbits is greater than 15.8 g/kg.
Executive summary:

The acute dermal toxicity of Trimethylolpropane Monoallyl Ether was determined in a study conducted on groups of 4 male albino rabbits administered the test material via dermal application. The fur was clipped from the entire trunk of each test animal and Trimethylolpropane Monoallyl Ether was applied by a cathether at concentrations of 3.98, 7.95 and 15.8 g/kg to the clipped area and was held in place using an impervious plastic cover. The test material remained in place for 24 hours. Any signs of toxicity were observed on removal of the test material and further observations were made over a 14 day observation period.

No mortalities were observed at any concentration over the course of the study. When dosed at 15.8 g/kg, some skin necrosis was observed. The LD50of Trimethylolpropane Monoallyl Ether by skin penetration for male albino rabbits is greater than 15.8 g/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
15 800 mg/kg bw
Quality of whole database:
Klimisch score = 2. The single study available was a range-finding investigation conducted prior to acceptance of GLP and test guidelines but the data are acceptable.

Additional information

Acute oral toxicity

The acute oral LD50 of 2 -allyloxymethyl-2 -ethylpropanediol in the rat is 4930 mg/kg bw (McNerney, 1961).

Acute dermal toxicity

The acute dermal LD50 of 2 -allyloxymethyl-2 -ethylpropanediol in the rabbit was found to be > 15800 mg/kg bw (McNerney, 1961).

Acute inhalation toxicity

A waiver is proposed for acute inhalation studies in accordance with Column 2 of Annex VIII of the REACH Regulation on the basis that acute toxicity data are available for the oral and dermal routes, showing that the 2 -allyloxymethyl-2 -ethylpropanediol is of low inherent acute toxicity. Inhalation is not predicted to be a significant route of exposure based on the physicochemical properties of the substance. The substance is a non-volatile liquid and the use pattern indicates that significant inhalation exposure is unlikely. No additional testing is therefore warranted.


Justification for selection of acute toxicity – oral endpoint
The test was the sole study available.

Justification for selection of acute toxicity – dermal endpoint
The test was the sole study available.

Justification for classification or non-classification

Acute oral and dermal LD50 values of 4930 and 15800 mg/kg respectively have been reported for 2 -allyloxymethyl-2 -ethylpropanediol. The substance does not meet the criteria for classification for acute oral or dermal toxicity according to Directive 67/548/EEC or Regulation 1272/2008/EC.