Bis(2,6-diisopropylphenyl)carbodiimide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001-02-23 - 2001-10-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2,6-diisopropylphenyl)carbodiimide

EC Number:

218-487-5

EC Name:

Bis(2,6-diisopropylphenyl)carbodiimide

Cas Number:

2162-74-5

Molecular formula:

C25H34N2

IUPAC Name:

N,N'-bis[2,6-bis(propan-2-yl)phenyl]methanediimine

Details on test material:

- Name of test material: bis(2,6-diisopropylphenyl)carbodiimide
- Substance type: organic technical product
- Description : white solid
- Batch number : 0600181/009
- Date received : 19 July 2001
- Storage conditions : room temperature, in the dark

For the purpose of the study the test material was weighed out according to each animals individual bodyweight and moistened with distilled water prior to application.
The absorption of the test material was not determined.

Test animals

Species:

rat

Strain:

other: CD (Crl: CD® (SD) IGS BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS: Five male and five female Sprague-Dawley CD (Crl: CD® (SD) IGS BR)
- Source: Charles River (UK) Ltd, Margate, Kent, UK.
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: at least 200g
- Fasting period before study:
- Housing: On receipt the animals were randomly allocated to cages: individually (during the 24-hour exposure) or in groups of five (by sex) for the remainder of the study in suspended polypropylene cages furnished with wood flakes.
- Diet (e.g. ad libitum): Rat and Mouse SQC Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK, ad libitum
(The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.)
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: at least five days.
- Other a): The females were nulliparous and non-pregnant. Animal selection at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25°C.
- Humidity (%): 30 - 70%.
- Air changes (per hr): at least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
- Other : Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study.


The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: moistened with distilled water

Details on dermal exposure:

TEST SITE
- Area of exposure: an area of shorn skin (approximately 10% of the total body surface area, area used: back and flanks of each animal)
- % coverage:
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: yes (For the purpose of the study the test material was weighed out according to each animals individual bodyweight and moistened with distilled water prior to application.)

The appropriate amount of test material, moistened with distilled water, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area, area used: back and flanks of each animal). 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-hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place. After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.

Duration of exposure:

single application for 24 hours exposure

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. The clinical observations for females were not recorded on Day 9. This deviation was considered not to affect the purpose or integrity of the study.

After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H (1977) "Dermal and Eye Toxicity Tests".

Any other skin reactions, if present were also recorded. 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 appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

No specific information given

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths were recorded.

Clinical signs:

other: No signs of systemic toxicity. Signs of dermal irritation noted were very slight to well-defined erythema, very slight oedema, crust formation, desquamation and small superficial scattered scabs. Very slight to well-defined erythema was noted at the treat

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

No other findings recorded

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: EU-GHS

Conclusions:

The study was performed according to the OECD Guideline 402 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1).The validity criteria of the test system was fulfilled. The test material did not induce any signs of acute dermal toxicity. The test material was considered to be not toxic via the dermal exposure route under the conditions of the test, which is based on the LD50 values derived from this study (LD50 > 2000 mg/kg bw).The test material does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with EU labelling regulations Commission Directive 93/21/EEC.

Executive summary:

The acute dermal toxicity of bis(2.6-diisopropylphenyl)carbodiimide was investigated in rats (Driscoll, 2001, according to OECD 402). The test item was moistened with distilled water and applied in a dose of 2000 mg/kg bw under semiocclusive conditions for 24 h. No death occurred and all animals showed expected gains in bodyweight over the study period. Additionally no abnormalities were recorded in the gross pathology performed after sacrifice. So the dermal LD50 was identified as LD50>2000 mg/kg bw.