Linalool

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Although an old study (1970) and not fully compliant with OECD 402, and non GLP, the report is well documented, and the design is considered scientifically accepted.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1970

Report date:

1970

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

3 animals per dose group of unspecified sex, post exposure (observation) only 7 days, area exposed not specified, animal weight slightly too low, no information on housing conditions.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Linalool

EC Number:

201-134-4

EC Name:

Linalool

Cas Number:

78-70-6

Molecular formula:

C10H18O

IUPAC Name:

3,7-dimethylocta-1,6-dien-3-ol

Details on test material:

- Name of test material (as cited in study report): Linalool
- Physical state: clear liquid

Test animals

Species:

rabbit

Strain:

other: albino

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: approx. 1500 to 2300 g.

ENVIRONMENTAL CONDITIONS: No data

IN-LIFE DATES: No data

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Type of wrap if used: Saran Wrap

REMOVAL OF TEST SUBSTANCE
- Washing: Gently removed
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amounts applied: 2500, 5000 and 10000 mg/kg/bw
- Concentration: Undiluted

Duration of exposure:

24 hours

Doses:

2500, 5000 and 10000 mg/kg/bw

No. of animals per sex per dose:

3

Control animals:

yes, concurrent no treatment

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: observation: daily; weighing: at start and termination (at 7 days) of the study
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, hematology and clinical chemistry were conducted on survivors at five days of the studies.
Hematology: Erythrocyte, leucocyte and differential leucocyte counts; hematocrit; hemoglobin.
Clinical chemistry: Serum glutamic oxaloacetic transaminase (SCOT): glucose; blood urea nitrogen (BUN); serum alkaline phosphatase (SAP); total serum protein; serum albumin; bilirubin; lactic acid dehydrogenase (LDH); cholesterol; serum calcium; serum phosphate; and uric acid, using the SMA-12 methods.

Statistics:

The acute dermal LD50 was calculated by the method of Weil (Biometrics 8, 3, p.249, Sept., 1952).

Results and discussion

Preliminary study:

Not applicable

Effect levels

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

5 610 mg/kg bw

95% CL:

>= 3 578 - <= 8 374

Mortality:

At 5000 mg/kg bw one out of three animals died at day 5.
At 10000 mg/kg bw all three rabbits were dead within the first 24 hours of the study.

Clinical signs:

other: - Other observations: Signs of intoxication were depression, coma and death. Signs developed within 24 hours following application of the test material, and survivors were normal after 5 days. On removal of the bandages, the skins of the rabbits at all tr

Gross pathology:

At autopsy no significant gross pathology was noted which could be attributed to the dermal application of the test substance.

Other findings:

- Other observations: All hematology and clinical chemistry values, conducted on survivors at five days of the studies, appeared to be within normal limits and are comparable to control values generated in this laboratory.

Any other information on results incl. tables

Not relevant

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 of linalool in rabbits is calculated to be 5610 mg/kg, with confidence limits of 8374 - 3578 mg/kg, under the conditions of this study. The substance does not need to be classified for acute dermal toxicity according to the criteria outlined in Regulation (EC) 1272/2008 (CLP/EU-GHS).

Executive summary:

The substance has been tested in an acute dermal toxicity test (similar to OECD 402, test system: Rabbit). Three dose levels, 2500, 5000 and 10000 mg/kg/bw, were applied undiluted for 24 hours. Untreated animals served as control.

On removal of the bandages, the skins of the rabbits at all treatment levels appeared blanched, with moderate erythema and slight edema of the skin surrounding the blanched areas. At 24 hours after removal, the skin of surviving rabbits appeared normal.

At 5000 mg/kg bw one out of three animals died at day 5. At 10000 mg/kg bw all three rabbits were dead within the first 24 hours of the study.

All hematology and clinical chemistry values, conducted on survivors at five days of the studies, appeared to be within normal limits and are comparable to control values generated in this laboratory. At seven days the surviving rabbits showed a normal weight gain for the period (at 2500 and 5000 mg/kg).

At autopsy no significant gross pathology was noted which could be attributed to the dermal application of the test substance.

Signs of intoxication were depression, coma and death. Signs developed within 24 hours following application of the test material, and survivors were normal after 5 days.

The substance does not need to be classified for acute dermal toxicity according to criteria Regulation (EC) 1272/2008/EC), as the LD50 is calculated to be 5610 mg/kg bw, with confidence limits of 8374 - 3578 mg/kg bw, under the conditions of this study.