1,2-diethoxypropane

Endpoint summary

Description of key information

Skin irritation (in vivo): Not irritating (equivalent or similar to OECD 404/GLP)

Serious eye damage/eye irritation (in vivo): Not irritating (equivalent or similar to OECD 405/GLP)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17th August 1991 - 2nd Decmber 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

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:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna UK Limited, Abbots Ripton Road, Wyton, Huntingdon
- Age at study initiation: young adult
- Housing: The rabbits were housed individually in aluminium cages with grid floors beneath which were peat moss filled trays.
- Diet: Standard Rabbit Diet, supplied by Special Diets
Services, 1 Stepfield, Witham, Essex, CM8 3AD ad libitum
- Water: tap water ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-20 °C
- Humidity (%): 57%
- Photoperiod (hrs dark / hrs light): A 12 h light/dark cycle was in operation

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Ethylene glycol diethyl ether (ethyl glyme),

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.5 mL
- Concentration (if solution):undiluted

0.5mL of the control material, ethylene glycol diethyl ether (ethyl glyme) was also applied.

Duration of treatment / exposure:

4 hrs

Observation period:

1, 24, 48 and 72 h after patch removal. Further assessments were carried out at 5, 6, 8, 9, 10 and 11 days after patch removal to determine the reversibility of responses.

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: The hair was clipped from the dorsal area of the trunk of each rabbit approximately 24 h before treatment. Care was taken to avoid abrading the skin.
- % coverage: The test and control materials (0.5 ml) were applied to intact skin on each rabbit under 2.5 cm x 2.5 cm patches of gauze.

- Type of wrap if used: Due to the volatility of the test material, the patches were covered with Sleek, an occlusive dressing, which remained in position for 4 h.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The patches were removed and the skin wiped with water dampened tissues to remove surplus test material without altering the existing response or the integrity of the epidermis.
- Time after start of exposure: After 4 hr exposure period

OBSERVATION TIME POINTS
(indicate if minutes, hours or days)
1, 24, 48 and 72 h after patch removal. Further assessments were carried out at 5, 6, 8, 9, 10 and 11 days after patch removal to determine the reversibility of responses.

SCORING SYSTEM:
- Method of calculation: The daily scores for erythema and oedema for the test and control material at the 24, 48 and 72 h assessments were totalled and the mean was calculated. This mean value is expressed as a mean irritation score for each material. The Draize scoring system was used (Appendix).

Irritation parameter:

erythema score

Basis:

other: animals 1 & 2

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

other: animals 1 & 2

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 6 days

Irritation parameter:

erythema score

Basis:

other: animals 1 & 2

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 6 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 11 days

Remarks:

Erythema = 1

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 11 days/Erythema = 1

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

overall irritation score

Remarks:

erythema

Basis:

animal: 1,2,3

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

not fully reversible within: 11 days

Remarks:

Animal #3 erythema = 1

Irritation parameter:

overall irritation score

Remarks:

oedema

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

overall irritation score

Remarks:

oedema

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

overall irritation score

Remarks:

oedema

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritant / corrosive response data:

Following a 4 h application of both the test and control materials, very slight to well defined erythema and very slight to slight oedema were noted up to 72 h after patch removal. At 5 days skin reactions deteriorated at a test site treated with test material and a test site treated with control material on one rabbit.

Interpretation of results:

GHS criteria not met

Conclusions:

In an in vivo skin irritation study in male New Zealand rabbits, the substance 1,2-Diethoxypropane was not irritating.

Executive summary:

In a primary dermal irritation study (8280), 3 male rabbits were dermally exposed (dorsal area of the trunk; occlusive) to 0.5mL of undiluted 1,2-Diethoxypropane for 4 hours. The substance was removed after 4 hrs with washing. Animals were observed at 24, 48 and 72 hrs for overall irritation scores and up to 11 days for reversibility. Irritation was scored by the method of Draize.

The overall irritation score (erythema) for all animals was 1.33. In only 1 animal (#3) the irritation was not fully reversible at Day 11 (erythema = 1). The overall irritation score (oedema) for animal #1 was 0. The overall irritation score (oedema) for animal #2 was 1.33 (fully reversible within 10 days). The overall irritation score (oedema) for animal #3 was 0.66 (fully reversible within 8 days). The observations were not extended to 14 days. In only 1 animal (#3) was the erythema not fully reversible at Day 11 (erythema = 1). Overall, based on the CLP criteria, the substance is not irritating.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19th August 1991 - 2nd December 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

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:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Interfauna UK Limited, Abbots Ripton Road, Wyton, Huntingdon
- Age at study initiation: young adult
- Housing: The rabbits were housed individually in aluminium cages with grid floors beneath which were peat moss filled trays.
- Diet: Standard Rabbit Diet, supplied by Special DietsServices, 1 Stepfield, Witham, Essex, CM8 3AD ad libitum
- Water: tap water ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C
- Humidity (%): 60%
- Photoperiod (hrs dark / hrs light): A 12 h light/dark cycle was in operation

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.1 mL

Duration of treatment / exposure:

The eye was not washed after treatment.

Observation period (in vivo):

1, 24, 48 and 72 h after instillation.

Number of animals or in vitro replicates:

3 males

Details on study design:

Approximately 24 h before test commencement; both eyes of the rabbits were examined and only animals with no ocular defects were used in the test.The rabbit was held firmly but gently and the test material placed into the right eye by gently pulling the lower eyelid away from the eyeball to form a sac into which the test material was dropped. The lids were then gently held together for one or 2 s. One rabbit was treated first and observed 1 h after instillation for signs of severe irritation. As none were noted, the remaining 2 rabbits were then treated the following day.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: The OECD Recommended Scoring System in OECD 405 was used.

TOOL USED TO ASSESS SCORE: The eyes were examined for irritation, using a hand held magnifier and pen torch (Pifco)

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal: 2,3

Time point:

other: 48/72 hrs

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Details of reaction scores are given in the Table. No corneal or iridial responses were noted. Slight conjunctival redness and chemosis and a slight discharge were noted up to 24 h post instillation. Full recovery was noted in all treated eyes at 48 h post instillation.

Interpretation of results:

GHS criteria not met

Conclusions:

In an in vivo eye irritation study in New Zealand rabbits, the substance 1,2-Diethoxypropane is not irritating.

Executive summary:

In a primary eye irritation study (8281), 0.1mL of 1,2-Diethoxypropane (undiluted) was instilled into the conjunctival sac of the right eye of young adult New Zealand White rabbits (3 males). The eye was not washed after instillation of the test article. Animals were observed for 1 hr, 24 hr, 48 hr and 72 hrs after dosing. Irritation was scored by the method of Draize.

The following mean values, based on the results from the 24, 48 and 72 hour readings were calculated - cornea opacity: 0; iris lesion: 0; oedema of conjunctiva (chemosis): 0; redness of conjunctiva: 0.33 (fully revsersible).

In this study, 1,2-Diethoxypropane is not an eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion:

There is no in vitro skin irritation test available for 1,2-Diethoxypropane. There is one in vivo skin irritation test in rabbits available.

In a primary dermal irritation study (equivalent or similar to OECD 404/GLP), 3 male rabbits were dermally exposed (dorsal area of the trunk; occlusive) to 0.5mL of undiluted 1,2-Diethoxypropane for 4 hours. The substance was removed after 4 hrs with washing. Animals were observed at 24, 48 and 72 hrs for overall irritation scores and up to 11 days for reversibility. Irritation was scored by the method of Draize. The overall irritation score (erythema) for all animals was 1.33. In only 1 animal (#3) the irritation was not fully reversible at Day 11 (erythema = 1). The overall irritation score (oedema) for animal #1 was 0. The overall irritation score (oedema) for animal #2 was 1.33 (fully reversible within 10 days). The overall irritation score (oedema) for animal #3 was 0.66 (fully reversible within 8 days). The observations were not extended to 14 days. In only 1 animal (#3) was the erythema not fully reversible at Day 11 (erythema = 1). Overall, based on the CLP criteria, the substance is not irritating.

Serious eye damage/eye irritation:

There is no in vitro eye irritation test available for 1,2-Diethoxypropane. There is an in vivo eye irritation study in rabbits available.

In a primary eye irritation study (equivalent or similar to OECD 405/GLP), 0.1mL of 1,2-Diethoxypropane (undiluted) was instilled into the conjunctival sac of the right eye of young adult New Zealand White rabbits (3 males). The eye was not washed after instillation of the test article. Animals were observed for 1 hr, 24 hr, 48 hr and 72 hrs after dosing. Irritation was scored by the method of Draize. The following mean values, based on the results from the 24, 48 and 72 hour readings were calculated - cornea opacity: 0; iris lesion: 0; oedema of conjunctiva (chemosis): 0; redness of conjunctiva: 0.33 (fully revsersible). In this study, 1,2-Diethoxypropane is not an eye irritant.

These studies are suitable to use the in human health 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) is not classified for skin irritation/corrosion or serious eye damage/eye irritation when considering the criteria outlined in Annex I of 1272/2008/EC.