reaction products of 2-Propenoic acid (2 moles) and Neopentylglycol hydroxypivalate (1 mole)

Endpoint summary

Description of key information

The acute toxicity of the registered substance has been evaluated for the oral and dermal route.

The oral study available showed no mortality or adverse systemic toxicity at the limit dose of 2000 mg/kg bw in rats.

In the three dermal studies, no mortality or adverse systemic toxicity at the limit dose of 2000 mg/kg bw were observed in rats.

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:

March - April 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Orient Bio Co., Ltd, korea
- Age at study initiation: 8/9 weeks old
- Weight at study initiation: 201.1-218.1 g
- Fasting period before study: yes
- Housing: by 3
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.6-22.2
- Humidity (%): 47.1-52.6
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

For 2000 mg/kg bw treatment to the animals, the test substance suspended with autoclaved distilled water to bring the formulation to 200 mg/mL test substance.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were carefully observed for 4 hours after treatment and then an once every day for 14 days. Bodyweight was measured animal receipt day, animal allocation day, just before treatment and on day 7 and 14 after the administration
- Necropsy of survivors performed: yes, on the end of study period, all animals were examined for external findings.

Statistics:

no

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality was observed.

Clinical signs:

other: Clinical signs related with the test substance in all animals were not observed during the observation period.

Gross pathology:

In all animals, there were no lesions caused by administration of the test substance.

Other findings:

no

Interpretation of results:

GHS criteria not met

Conclusions:

Based on these results, there were no mortality when the test substance was acute administrated orally at a dose volume of 2000 mg/kg bw in female rats, the oral LD50 is higher than 2000 mg/kg bw.

Executive summary:

The acute oral toxicity study was conducted to the SD rats. The test substance was administrated only one time by oral route at a dose volume of 2000 mg/kg bw. Three animals were used for each step that divided 1 step and 2 step. Mortality, clinical signs, body weights and necropsy findings were observed for 14 days. No mortality was observed. Clinical signs related with the test substance in all animals were not observed during the observation period. All tested animals showed normal gains in body weights. In all animals, there were no lesions caused by administration of the test substance. Based on these results, there were no mortality when the test substance was acute administrated orally at a dose volume of 2000 mg/kg bw in female rats, the oral LD50 is higher than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is considered to be reliable with a klimish of 1.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK limited, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 12 weeks
- Weight at study initiation: at least 200g
- Fasting period before study: no data
- Housing: individually during the treatment , and in group of 4/5 by sex
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day before treatment, the back and flanks of each animal were clipped free of hair.
Volume dose : 1.93 ml/kg
The calculated volume of test material, as received, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The animals were caged individually for the 24 hours exposure period and for the remainder of the test. Shortly after dosing the dressings were examined to ensure that they were securely in place.
After the 24-hour contact period the bandage was carrefully removed and the treated skin and surrounding hair wiped with cottin wool moistened with distilled water to remove aby residual test material.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Using available information on the toxicity of the test material, a single group of animals (one male and one female) were initially treated. As no mortalities were noted, a further group of animals (4 males and 4 females) was similarly treated with the test material at a dose of 2000 mg/kg bw to give a total of 5 males and 5 females. After the 24- hour contact period the bandages were carefully removed and the treated skin and surrunding hair wiped with cotton wool moistened with distilled water remove any residual test material. These animals were returned to group housing for the remainder of the test meriod.
The animals were observed for deaths or overt signs of toxicity 30 min, 1, 2 , 4 hours after dosing and subsequently once daily for 14 days.
After removal of the dressing and subsequently once daily for 14 days, the test sites were examined for evidence of primary and scored according to the scale from Draize JH (1977) "Dermal and eye toxicity tests".
Individual bodyweights were recorded prior to application of the test material on Day 0 and on days 7 and 14.
At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearence of any macroscopic abnormalities was recorded. no tissues were retained.
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.

Statistics:

no

Preliminary study:

no

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

There were no deaths

Clinical signs:

other: there were no signs of systemic toxicity. Well-defined erythema was noted at the treatment sites of 4 males with a very slight erythema noted at the treatment sites of 3 females, 1 and 2 days after dosing. very slight erythema was noted at the treatment s

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Very slight to well-defined erythema was noted at the treatment sites of seven animals. Small superficial scattered scabs were noted at the treatment sites of 2 male animals with scab lifting at edges to reveal bleeding and a hardened light brown coloured scab also noted at the treatment site of one of these animals. Animals showed expected gains of bodyweight over the study period, except for one female which showed bodyweight loss during the first week but expected gain in bodyweight during the second week. No abnormalities were noted at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

In conclusion, the acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bw.

Executive summary:

The study was performed to assess the acute dermal toxicity of the test material in the Wistar strain rat. The method was deisgned to meet the requirements of the OECD guideline 402.

Initially, 2 animals (1F, 1M) were given a single, 24 -hour, semi-occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bw. Based on the results of the initial test, a further group of eight animals (4F, 4M) was similarly treated. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths, no signs of systemic toxicity. Very slight to well-defined erythema was noted at the treatment sites of seven animals. Small superficial scattered scabs were noted at the treatment sites of 2 male animals with scab lifting at edges to reveal bleeding and a hardened light brown coloured scab also noted at the treatment site of one of these animals. Animals showed expected gains of bodyweight over the study period, except for one female which showed bodyweight loss during the first week but expected gain in bodyweight during the second week. No abnormalities were noted at necropsy.

In conclusion, the acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

December 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

1984

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: harlan Olac Ltd, Bicester, Oxon, England
- Age at study initiation: 7-10 weeks
- Weight at study initiation: 201-248 g
- Fasting period before study:
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50-51
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Volume of administration: 1.90 ml/kg
One day prior to treatment hair was removed from the dorso-lumbar region of each rat with electric clippers exposing an area equivalent to approximately 10% of the total body surface.
The test substance was applied by spreading it evenly over the prepared skin. The treated area (approximately 50 mm x 50 mm) was then promptly covered with gauze which was held in place with a non-irritative dressing encircled firmly around the trunk.
At the end of the 24 hours exposure period, the dressings were carefully removed and the treated area of skin was washed with warm (30 to 40 °c) water and blotted dry with absorbent paper.
The day of dosing was designated Day 1.

Duration of exposure:

24h

Doses:

2000

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Cages of rats were checked at least twice daily for any mortalities.
Animals were observed soon after dosing and at frequent intervals for the remainded of Day 1 (a period of 7h). On subsequent days animals were observed once in the morning and agin at the end of the experimental day. This latter observation was at approximately 16.30 hours on week days or 11.30 on Saturdays, Sundays and public holidays. The nature and the severity of the clinical signs and time were recorded at each observation. All animals were observed for 14 days after dosing.
Local dermal irritation at the treatment site was assessed daily using the following numerical system.
Individual bodyweights were recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes were calculated.
All animals were killed on Day 15 by cervical dislocation and were subjected to a macrospcopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearence of all examined tissues was recorded.

Statistics:

no

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

There were no deaths

Clinical signs:

other: There were no signs of systemic reaction to treatment. Local reactions: slight to well-defined erythema was observed at the sites of application of the test substance for all rats on days 2 to 4 accompanied by slight oedema in all rats on Day 3 ; well-def

Gross pathology:

No macroscopic abnormalities were observed for animals killed on Day 15.

Other findings:

no

Interpretation of results:

GHS criteria not met

Conclusions:

The acute lethal dermal dose of the test material was found to be greater than 2000 mg/kg bw.

Executive summary:

A study was performed to assess the acute dermal toxicity of the test material to the rat. A group of ten rats (5M/5F) was given a single dermal application of the test substance, as supplied, at a dose level of 2000 mg/kg bw. All animals were killed and axamined macroscopically on Day 15, the end of the observation period.

There were no deaths and no signs of systemic reaction to treatment. Slight to well-defined erythema was observed at the sites if application of the test substance for all rats on Days 2 to 4 accompanied by slight oedema in all rats on Day 3 ; well-defined erythema only persisted in five rats to Day 5 with slight oedema seen in one female on Day 6. There were no other dermal changes and irritation had resoled by Day 7. Slightly low bodyweight gains were recorded for three females on Day 8 and for one male and 3 females on Day 15. No abnormalities were recorded at the macroscopic examination on Day 15.

The acute lethal dermal dose of the test material was found to be greater than 2000 mg/kg bw.

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

December 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

1984

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: harlan Olac Ltd, Bicester, Oxon, England
- Age at study initiation: 7-10 weeks
- Weight at study initiation: 201-248 g
- Fasting period before study:
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50-51
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Volume of administration: 1.93 ml/kg
One day prior to treatment hair was removed from the dorso-lumbar region of each rat with electric clippers exposing an area equivalent to approximately 10% of the total body surface.
The test substance was applied by spreading it evenly over the prepared skin. The treated area (approximately 50 mm x 50 mm) was then promptly covered with gauze which was held in place with a non-irritative dressing encircled firmly around the trunk.
At the end of the 24 hours exposure period, the dressings were carefully removed and the treated area of skin was washed with warm (30 to 40 °c) water and blotted dry with absorbent paper.
The day of dosing was designated Day 1.

Duration of exposure:

24h

Doses:

2000

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Cages of rats were checked at least twice daily for any mortalities.
Animals were observed soon after dosing and at frequent intervals for the remainded of Day 1 (a period of 7h). On subsequent days animals were observed once in the morning and agin at the end of the experimental day. This latter observation was at approximately 16.30 hours on week days or 11.30 on Saturdays, Sundays and public holidays. The nature and the severity of the clinical signs and time were recorded at each observation. All animals were observed for 14 days after dosing.
Local dermal irritation at the treatment site was assessed daily using the following numerical system.
Individual bodyweights were recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes were calculated.
All animals were killed on Day 15 by cervical dislocation and were subjected to a macrospcopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearence of all examined tissues was recorded.

Statistics:

no

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

There were no deaths

Clinical signs:

other: There were no signs of systemic reaction to treatment. Local reactions: slight erythema was observed at the sites of application of the test substance for all rats on days 2 and 3. There were no other dermal changes and irritation had resolved by Day 4.

Gross pathology:

No macroscopic abnormalities were observed for animals killed on Day 15.

Other findings:

no

Interpretation of results:

GHS criteria not met

Conclusions:

The acute lethal dermal dose of the test material was found to be greater than 2000 mg/kg bw.

Executive summary:

A study was performed to assess the acute dermal toxicity of the test material to the rat. A group of ten rats (5M/5F) was given a single dermal application of the test substance, as supplied, at a dose level of 2000 mg/kg bw. All animals were killed and axamined macroscopically on Day 15, the end of the observation period.

There were no deaths and no signs of systemic reaction to treatment. Slight erythema was observed at the sites if application of the test substance for all rats on Days 2 and 3. There were no ohter dermal changes and irritation had resolved by Day 4. Slightly low bodyweight gains were recorded for 2 males and 4 females on Day 8 and for 2 males and 2 females on Day 15. No abnormalities were recorded at the macroscopic examination on Day 15.

The acute lethal dermal dose of the test material was found to be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The key and supporting studies are considered to be reliable with a klimish of 1.

Additional information

Oral acute toxicity study (KTR 2009):

The acute oral toxicity study was conducted to the SD rats. The test substance was administrated only one time by oral route at a dose volume of 2000 mg/kg bw. Three animals were used for each step that divided 1 step and 2 step. Mortality, clinical signs, body weights and necropsy findings were observed for 14 days. No mortality was observed. Clinical signs related with the test substance in all animals were not observed during the observation period. All tested animals showed normal gains in body weights. In all animals, there were no lesions caused by administration of the test substance. Based on these results, there were no mortality when the test substance was acute administrated orally at a dose volume of 2000 mg/kg bw in female rats, the oral LD50 is higher than 2000 mg/kg bw.

Dermal acute toxicity studies :

The key study is the most recent study (Sanders 2009).

The study was performed to assess the acute dermal toxicity of the test material in the Wistar strain rat. The method was deisgned to meet the requirements of the OECD guideline 402.

Initially, 2 animals (1F, 1M) were given a single, 24 -hour, semi-occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bw. Based on the results of the initial test, a further group of eight animals (4F, 4M) was similarly treated. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths, no signs of systemic toxicity. Very slight to well-defined erythema was noted at the treatment sites of seven animals. Small superficial scattered scabs were noted at the treatment sites of 2 male animals with scab lifting at edges to reveal bleeding and a hardened light brown coloured scab also noted at the treatment site of one of these animals. Animals showed expected gains of bodyweight over the study period, except for one female which showed bodyweight loss during the first week but expected gain in bodyweight during the second week. No abnormalities were noted at necropsy.

In conclusion, the acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bw.

Both supporting studies (Denton 1993a, 1993b) showed the same results: absence of mortality and systemic effects at the limit dose of 2000 mg/kg bw in rats.

Justification for classification or non-classification

Based on the available data, no classification for acute toxicity is required for the registered substance according to the Regulation EC n°1272/2009.