4-isopropyl-m-cresol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

February 26 to March 04, 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted similar to OECD test Guideline No. 401 and before the GLP compliance. 7 days observation followed instead of 14 days observation

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 1

Reference Type:

other: Unpublished data submitted by CTFA

Title:

Unnamed

Year:

1980

Reference 2

Reference Type:

review article or handbook

Title:

Final Report on the Safety Assessment of sodium p-chloro-m-cresol, p-chloro-m-cresol, chlorothymol, mixed cresols, m-cresol, o-cresol, p-cresol, isopropyl cresols, thymol, o-cymen-5-ol and carvacrol

Author:

Cosmetic Ingredient Review (CIR) expert panel

Year:

2006

Bibliographic source:

International Journal of toxicology, 25(Suppl.1):29-127, 2006

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Old study before GLP. No details about the substance (purity, conditions of storage, etc). 7 days observation followed instead of 14 days observation.

Principles of method if other than guideline:

Groups of mice (7 mice of both sexes/ dose) were administered the test substance by gavage at two different doses (10 mL/kg bw and 22 mL/kg bw). The animals were observed for 7 days before necropsy. The LD50 is determined.

GLP compliance:

no

Remarks:

Study conducted before GLP compliance applied

Test type:

standard acute method

Limit test:

no

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

Details on test material:

- Name of test material (as cited in study report): Biosol (Iso-propyl m-cresol)
- Source: Matsumoto Kosho Co., Ltd.
- Physical state: liquid
- Analytical purity: >99%
- Lot/batch No.: no data

Test animals

Species:

mouse

Strain:

other: Slc-ddy strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Shizuoka Test Animal Laboratory
- Age at receipt: 4 weeks
- Weight at study initiation: 20.0-24.1 g (males); 19.0-22.3 g (females)
- Fasting period before study: None
- Housing: Seven mice were housed in the plastic cages (manufactured by Japan Klare Co., Ltd.) wood out in the bottom.
- Diet: Solid food (CE-2; manufactured by Japan Klare Co., Ltd.), ad libitum
- Water, ad libitum
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature: 23 ± 1 °C
- Humidity: 55 ± 5 %

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

10% test substance in an aqueous suspension of 0.5% CMC was given by stomach tube to two groups of both sexes mice.

Doses:

10 and 22 mL/kg bw (1000 and 2200 mg/kg bw, respectively)

No. of animals per sex per dose:

7 mice of both sexes/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: General conditions and mortality were observed for one week after dosing. Each mouse was weighed every day (except Sunday).
- Necropsy of survivors performed: Yes; Survivors were sacrificed under the ether anesthesia on day 8 after dosing.

Statistics:

No data

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 200 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: No clinical signs were observed.

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:

Oral LD50 (male and female) > 2200 mg/kg bw. Under the test conditions, parathymol is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

Executive summary:

In an acute oral toxicity study performed equivalent to OECD Guideline No. 401, groups of mice (7 mice of both sexes/ dose) was given a single oral dose of 10% CMC diluted Biosol at dose level of 10 and 22 mL/kg bw corresponding to 1000 and 2200 mg/kg bw, respectively. Animals were observed daily for mortality, clinical signs and bodyweights for 7 days. At the end of the study the surviving animals were sacrificed for macroscopic examination.

No mortality or systemic toxicity was observed up to the end of observation. No body weight change was observed in males at 10 mL/kg bw. Males at 22 mL/kg bw and females at 10 and 22 mL/kg bw showed reduction in body weight gain on the 1st day after dosing. However, weight gain was normal thereafter. No abnormalities were noted at necropsy.

 

Oral LD50 (male and female) > 2200 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 oral toxicity endpoint.