Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: LD50 (male/female) > 2000 mg/kg bw (equivalent or similar to OECD 401/GLP)

Acute dermal toxicity: LD50 (male/female) > 2000 mg/kg bw (equivalent or similar to OECD 402/GLP)

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:
16th July 1991 - 2nd December 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Manston Road, Margate, Kent
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: 171-216 g
- Fasting period before study: Yes; overnight prior to dosing and 3 h post dosing
- Housing: polypropylene cages with mesh floors suspended over absorbent paper lined trays, with a maximum of 5 animals per cage.
- Diet: Rat and Mouse No. 1 Maintenance Diet, supplied by Special Diets Services, 1 Stepfield, Witham, Essex, CM8 3AD ad libitum
- Water: Tap water ad libitum
- Acclimination: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C mean relative humidity was 55%.
- Humidity (%): Mean relative humidity was 55%
- Photoperiod (hrs dark / hrs light): A 12 h light/dark cycle was in operation

Route of administration:
oral: gavage
Vehicle:
other: Tween 80
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: Observed frequently on the day of dosing and once daily for 14 days following dosing.
- Frequency of weighing: They were weighed immediately prior to dosing, 7 days after dosing and at sacrifice at the end of the 14 day observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths.
Clinical signs:
Clinical signs were noted 30 mins - 4 hrs after dosing, included piloerection, soiled coat, reduced activity, ataxia and subdued behaviour.
Body weight:
Body weight gains were acceptable.
Gross pathology:
There were no abnormalities detected at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study in Sprague Dawley rats the LD50 (male/female) was >2000 mg/kg bw.
Executive summary:

In an acute oral toxicity study (8279), groups (5/sex) of Sprague Dawley rats were given a single oral dose of 1,2-Diethoxypropane in Tween-80 by gavage at 2000 mg/kg bw. Animals were then observed for 14 days.

LD50 (male/female): > 2000 mg/kg bw.

Clinical signs were noted 30 mins - 4 hrs after dosing, included piloerection, soiled coat, reduced activity, ataxia and subdued behaviour. There was no mortality and no abnormalities were detected at necropsy. Body weight gains were acceptable.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
There is one study available and it has a Klimisch score of 2.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
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:
16th July 1991 - 3rd December 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- lot/batch No.of test material: 9059

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: The test material, a colourless liquid, was stored in the dark under ambient conditions.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Manston Road, Margate, Kent
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: 171-216 g
- Fasting period before study: Yes; overnight prior to dosing and 3 h post dosing
- Housing: polypropylene cages with mesh floors suspended over absorbent paper lined trays, with a maximum of 5 animals per cage.
- Diet: Rat and Mouse No. 1 Maintenance Diet, supplied by Special Diets Services, 1 Stepfield, Witham, Essex, CM8 3AD ad libitum
- Water: Tap water ad libitum
- Acclimination: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C mean relative humidity was 55%.
- Humidity (%): Mean relative humidity was 55%
- Photoperiod (hrs dark / hrs light): A 12 h light/dark cycle was in operation
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Rats were prepared by clipping the backs free of hair, approximately 24 h before application of the test material. Care was taken to avoid abrading the skin. The test material was applied evenly onto a gauze dressing which was applied to the shaved back of each rat.
- % coverage: 10%
- Type of wrap if used: Strip of non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin wiped with a water dampened tissue to remove excess test material.
- Time after start of exposure: 24 hrs
Duration of exposure:
24 hrs
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: The rats were observed frequently on the day of dosing and once daily for 14 days following dosing
- Frequency of observations and weighing: They were weighed immediately prior to dosing, 7 days after dosing and at sacrifice at the end of the 14 day observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no mortalities.
Clinical signs:
There were no clinical signs.
Body weight:
Body weight gains were acceptable.
Gross pathology:
No abnormalities were detected at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study in Sprague-Dawley rats, the LD50 (male/female) was >2000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study (8279), groups of Sprague-Dawley rats (5/sex) were dermally exposed (10% body surface area; occlusive) to 1,2-Diethoxypropane for 24 hours. The substance was removed after 24 hrs with washing. Animals were then observed for 14 days.

Dermal LD50 (Males/Females) = >2000 mg/kg bw

There was no mortality and no clinical signs were noted. No abnormalities were detected at necropsy. Body weight gains were acceptable.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
There is one study available and it has a Klimisch score of 2.

Additional information

Acute oral toxicity

There is one oral toxicity study in the rat available.

In an acute oral toxicity study (equivalent or similar to OECD 401/GLP), groups (5/sex) of Sprague Dawley rats were given a single oral dose of 1,2-Diethoxypropane in Tween-80 by gavage at 2000 mg/kg bw. Animals were then observed for 14 days. Clinical signs were noted 30 mins - 4 hrs after dosing, included piloerection, soiled coat, reduced activity, ataxia and subdued behaviour. There was no mortality and no abnormalities were detected at necropsy. Body weight gains were acceptable. The acute oral LD50 (males/females) was >2000 mg/kg bw.

Acute dermal toxicity

There is one dermal toxicity study in the rat available.

In an acute dermal toxicity study (equivalent or similar to OECD 402/GLP), groups of Sprague-Dawley rats (5/sex) were dermally exposed (10% body surface area; occlusive) to 1,2-Diethoxypropane for 24 hours. The substance was removed after 24 hrs with washing. Animals were then observed for 14 days. There was no mortality and no clinical signs were noted. No abnormalities were detected at necropsy. Body weight gains were acceptable. The acute dermal LD50 (males/females) was >2000 mg/kg bw.

These studies are acceptale to use in the human health risk assessment.

Justification for classification or non-classification

Based on the available information in the dossier, the substance 1,2-Diethoxypropane (CAS No. 10221-57-5) does not need to be classified for acute toxicity or specific target organ toxicity - single exposure, when the criteria outlined in Annex I of 1272/2008/EC are applied.