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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
3 May - 15 June 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was performed according to methods similar to OECD guideline 402 and under GLP conditions. Test groups included only 3 animals of each sex and included animals with abraded skin.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
For each of four dose levels three male and three female rabbits were used and the skin of two males and one female was abraded
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Constituent 1
Reference substance name:
Eucalyptus Citriodora
IUPAC Name:
Eucalyptus Citriodora
Details on test material:
- Name of test material: Eucalyptus Citriodora

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: a suitably licensed dealer
- Age at study initiation: no data
- Weight at study initiation: 1.47 to 2.25 kg
- Fasting period before study: no data
- Housing: galvanized or stainless steel cages
- Diet: growth and maintenance ration from a commercial producer
- Water: ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: mid dorsal area of the trunk between the scapulae and pelvis
- % coverage: no data
- Type of wrap if used: impermeable plastic wrap fixed with adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the excess test article was gently wiped off
- Time after start of exposure: 24 hours

TEST MATERIAL
- Single dermal application (volumetric dosing).
Duration of exposure:
24 hours
Doses:
250, 1000, 2000, 3500 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation at 1, 3, 6, and 24 hours; once per day thereafter. Weighing on the day of dosing, after 14 days or upon death
- Necropsy of survivors performed: yes, animals sacrificed at the end of the 14 day observation period as well as non-survivors
- Other examinations performed: clinical signs

Results and discussion

Preliminary study:
Successive dose levels were chosen on the basis of the mortality observed at previously performed test level.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 480 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 530 - < 4 002
Mortality:
250 mg/kg: none
1000 mg/kg: 1M
2000 mg/kg: 2M, 1F
3500 mg/kg: 2M, 1F
Clinical signs:
other: 250 mg/kg: none 1000 mg/kg: none 2000 mg/kg after 24 hours: 1M, 1F slight depression, 1M severe depression 3500 mg/kg after 6 hours: 1M slight depression; after 24 hours: 1M; 1M, 2F slight depression
Gross pathology:
250 mg/kg: none
1000 mg/kg: : 2M, 3F blanched skin; 1M faeces loose, 1M liver and lungs discoulered, 2F scab formed over test site, sloughing
2000 mg/kg: 2M, 2 F blanched skin; 1 M 1 F skin slightly reddened and swollen, blanched; 1M kidneys pitted; 1F yellow-white liver lesions, 0.2 - 0.3 cm, firm; 2F scab formed over test site, sloughing
3500 mg/kg: 2M 1F skin slightly reddened and swollen, blanched; 1M, 2F scab formed over test site, sloughing

Any other information on results incl. tables

Draize scores:

- 250 mg/kg: all animals 1/1;

- 1000 mg/kg: 2/1, 0/0, 2/2, 1/1, 2/2, 2/1;

- 2000 mg/kg: 1/2, 1/2, 1/1, 1/1;

- 3500 mg/kg: 1/2, 1/1, 1/2

The LD50 can be considered as a 'worst-case' value since animals with abraded skin were included in the calculation. It is expected that the LD50 would have been higher when all animals would have been tested with intact skin.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
based on CLP criteria
Conclusions:
Under the conditions of this study, the acute dermal LD50 in rabbits was calculated to be 2480 mg/kg bw. Based on this result, the test substance does not need to be classified in accordance with the criteria outlined in CLP (1272/2008/EC).
Executive summary:

Acute dermal toxicity was tested in a test similar to OECD guideline 402. New Zealand white rabbits were acclimated for at least 6 days and dosed in groups of six (3M:3F) at 250, 1000, 2000 and 3500 mg/kg bw. The skin of half the animals (2M:1F) was abraded. Each animal received a single dermal application of the test substance. The test sites were occluded for 24 hours after which the wrap and remaining substance was removed. Animals were observed for clinical signs and mortality 1, 3, 6 and 24 hours after treatment and daily thereafter for a total of 14 days. All animals were subjected to gross necropsy.

Mortality was observed starting from the 1000 mg/kg bw dose group (1 animal). In the highest dose groups 3 animals of each group died. Clinical signs were only noted in the 2 highest dose groups and included slight and severe depression. Gross necropsy showed no effects in the lowest dose groups. From the 1000 mg/kg bw dose group effects on skin (blanching, reddening, swelling, scab formation) and some internal organs (liver and lungs discoloured, kidneys pitted, liver lesions) were observed.

Based on these results, the LD50 was calculated to be 2480 (CI: 1530 - 4020) mg/kg bw and therefore the test substance does not need to be classified in accordance with the criteria outlined in CLP (1272/2008/EC).

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