4-isopropyl-m-cresol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From June 19 to July 03, 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in compliance with OECD Guideline No. 402 without any deviation.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

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

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Compliance Programme (inspected on March 12-14, 2014/ signed on May 12, 2014

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-isopropyl-m-cresol

EC Number:

221-761-7

EC Name:

4-isopropyl-m-cresol

Cas Number:

3228-02-2

Molecular formula:

C10H14O

IUPAC Name:

4-isopropyl-m-cresol

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report): Parathymol P16029
- Physical state: White crystalline solid
- Storage condition of test material: Room temperature in the dark

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, Bicester, Oxon, UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: At least 200 g
- Housing: Animals were housed individually during the 24 h exposure period and in groups of five by sex for the remainder of the study in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: Food (2014C Teklad Global Rodent diet supplied by, Harlan Laboratories UK Limited, Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: 15 changes/h
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From June 19 to July 03, 2014

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: moistened with dimethyl sulphoxide

Details on dermal exposure:

TEST ITEM FORMULATION AND EXPERIMENTAL PREPARATION
- For the purpose of the study the test item was weighed out according to each animal’s individual body weight and moistened with dimethyl sulphoxide prior to application.

TEST SITE
- Area of exposure: Back and flank area
- % coverage: The appropriate amount of test item, moistened with dimethyl sulphoxide, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area).
- 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 h contact period, the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with dimethyl sulphoxide followed by distilled water to remove any residual test item. The animals were returned to group housing for the remainder of the study period.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: Yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortality or clinical signs of toxicity at 0.5, 1, 2 and 4 h after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the Draize scale.
- Necropsy of survivors performed: Yes; at the end of the study animals were killed by cervical dislocation and subjected to gross necropsy.

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed.

Mortality:

No mortality was observed.

Clinical signs:

other: - No signs of systemic toxicity were noted during the observation period. - Dermal reactions: Very slight erythema (score 1) and hemorrhage of dermal capillaries were noted at the test sites of two males on Day 1; one male continued to show very slight er

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Dermal LD50 Combined > 2000 mg/kg bw.  Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and of the Directive 67/548/EEC. 

Executive summary:

In an acute dermal toxicity study (limit test) performed according to OECD Guideline No. 402 and in compliance with GLP, a group of Wistar (RccHan^TM:WIST) rats (5/sex) was given a single dermal application of the undiluted test material to intact skin of the back and flank area at a dose level of 2000 mg/kg bw. Test sites were covered with a semi-occlusive dressing for 24 h. Animals were observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination. Skin irritation was assessed and scored according to the Draize scale at 24 h after removal of the dressings and then daily for 14 days. 

No mortality or systemic toxicity was observed. Very slight erythema (score 1) and hemorrhage of dermal capillaries were noted at the test sites of two males on Day 1; one male continued to show very slight erythema (score 1) on Day 2. Very slight erythema (score 1) was noted at the test site of one female on Day 5 and crust formation was noted at the test sites of three females on Day 5. Crust formation persisted at the treatment site of two females from Days 6 to 8. Small superficial scattered scabs and glossy skin were noted at the test sites of two females from Days 5 to 8. All animals showed gains in body weight over the observation period. No abnormalities were noted at necropsy.

 

Dermal LD50 Combined > 2000 mg/kg bw

 

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and of the Directive 67/548/EEC. 

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.