Esterification product of castor oil and tetrahydromethyl-1,3-isobenzofuranedione

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Remarks:

The test was performed for registration purpose outside EU

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January-February 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

According to the Guidelines for the testing of chemicals “Acute Dermal Toxicity” (402) published by the Ministry of Environmental Protection of People’s Republic of China in the year of 2013.

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Esterification product of castor oil and tetrahydromethyl-1,3-isobenzofuranedione

EC Number:

700-064-6

Cas Number:

2105830-60-0

Molecular formula:

Not applicable as this is a UVCB substance

IUPAC Name:

Esterification product of castor oil and tetrahydromethyl-1,3-isobenzofuranedione

Test material form:

liquid: viscous

Details on test material:

- Name: Cyclohexene-1,2-dicarboxylic acid, methyl-, castor-oil alkyl esters
- Product Name: Multiester P97-463
- CAS No.: 2105830-60-0
- Batch No.: X24Jan17
- Physical State: viscous liquid
- Colour: amber
- Density: 1.06 g/cm³
- Active Components: 94%
- Expiry Date: 31 December 2018
- Storage Conditions: Room temperature, protected from light and kept in closed container to avoid air contact
- Safety Precautions: The routine hygienic procedures were sufficient to assure personnel health and safety.

Specific details on test material used for the study:

Test item code in the facility: 2017CO 16

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals
- Number of animals: 10 rats (5 females, 5 males). The females were nulliparous and non-pregnant.
- Age: 10-11 weeks at the commencement of each animal’s dosing.
- Range of body weights (dosing): Males: 295~300 g, Females: 247~272 g
- Physical check-up and acclimation: Physical check-up and acclimation were made to all animals imported. Healthy young adult animals were acclimatized to the laboratory conditions and housed two per cage for at least 5 days prior to the test. Clinical observations were performed daily during acclimation.
All animals were marked by the special animal markers on the hair and numbers written on cage cards. At the end of the necropsy, animals were also marked on the tails.

Husbandry
Animals were housed in Room A120-1 of the facility. Animals were raised in suspended, stainless steel cages on cage racks. There were 10 cages per layer, and 4 layers per rack.
Animals were housed individually during the test.
Temperature and humidity were controlled automatically and daily recorded. The values in the animal room were 20-25°C for temperature, and 40%-70% for humidity. A controlled light cycle was 12 hour light, 12 hour dark.
Food and water: Animals were provided sterilized diet with complete nutrition supplied by Beijing Keaoxieli Feed Co., LTD. (Product License No: SCXK (jing) 2014-0010, Batch No.17113221). Analysis reports of diet were supplied by the supplier. All the nutrition components and contaminants were within the permitted limits described in the national standard (GB 14924.3-2010 and GB 14924.2-2001). Water was purified by HT-R01000 purity system. Water analysis was conducted routinely analyzed (annually), and all parameters were within the permitted limits described in the national drinking water standard (8B5749-2006). The diet and water were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. Diet and water were available to the animals ad libitum during test.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Approximately 24 hours before the test, fur was removed from the dorsal area of the trunk of the test animals by shaving. Care was taken to avoid abrading the skin, which could alter its permeability. Clear area was about 40 cm2.
Dosing frequency: Dosing once for each animal.
The test item was applied evenly to the treatment area. The gauze (6×6.5 cm2) on no-irritating adhesive tape was placed over the treatment area and wrapped with a piece of medical self-adhesive bandage to hold the test substance in contact with the skin. The dressing was semi-occlusive. Shortly after dosing the dressing was examined to ensure that the animals cannot ingest the test item.
At the end of the exposure period for approximated 24 hours, residual test item was removed with cotton ball soaked with water.

Duration of exposure:

24 hours

Doses:

2000 mg/kg/bw

No. of animals per sex per dose:

5 male and 5 female

Control animals:

no

Details on study design:

A limit test at dose level of 2000mg/kg body weight was carried out in one group of 10 animals (5 males and 5 females). Clinical observations were made during the first 30 minutes, at 1, 2 and 4 hours after dosing and then once each day for up to 14 days. Individual weights of animals were determined. At the end of the test, a gross necropsy was performed on all animals under test.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths or moribund during the test.

Clinical signs:

There were no abnormal findings in all animals after dosing from the first day until the end of the test.

Body weight:

The body weight gain of the animals was within the range commonly recorded for this strain and age.

Gross pathology:

No abnormalities were found at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results, the acute dermal LD50 in rats for Cyclohexene-1,2-dicarboxylic acid, methyl-, castor-oil alkyl esters was as follows: Male/female rats: > 2000 mg/kg bw.
According to the GHS’s classification criteria of acute dermal toxicity, no classification is warranted.

Executive summary:

The study was performed to assess the acute dermal toxicity of Cyclohexene-1,2-dicarboxylic acid, methyl-, castor-oil alkyl esters in Sprague Dawley rats. The method was designed to meet the Guidelines for the testing of chemicals “Acute Dermal Toxicity” (402) published by the Ministry of Environmental Protection of People’s Republic of China in the year of 2013.

A limit test at dose level of 2000mg/kg body weight was carried out in one group of 10 animals (5 males and 5 females).Clinical observations were made during the first 30 minutes, and at 1, 2 and 4 hours after dosing and then once each day for up to 14 days. Individual weights of animals were determined. At the end of the test, a gross necropsy was performed on all animalsunder test.

Results

- Mortality: There were no deaths or moribund during the test.

- Clinical observations: There were no abnormal findings in all animals after dosing from the first day until the end of the test.

- Body Weights: The body weight gain of the animals was within the range commonly recorded for this strain and age. 

- Necropsy: No abnormalities were found at necropsy.

Conclusion

Based on the results, the acute dermal LD50 in rats for Cyclohexene-1,2-dicarboxylic acid, methyl-, castor-oil alkyl esters was as follows: Male/female rats: >2000 mg/kg/bw. According to the GHS’s classification criteria of acute dermal toxicity, no classifiaction is warranted.