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

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

821-997-6

Cas Number:

2136366-99-7

Molecular formula:

C11H16O6 to C21H32O8

IUPAC Name:

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

Test material form:

liquid

Test animals

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

Administration / exposure

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

Results and discussion

Preliminary study:

no

Effect levels

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.

Applicant's summary and conclusion

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.