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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:
9 August 2005 to 25 August 2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
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

Constituent 1
Chemical structure
Reference substance name:
Tall oil
EC Number:
232-304-6
EC Name:
Tall oil
Cas Number:
8002-26-5
Molecular formula:
Variable
IUPAC Name:
Tall Oil
Test material form:
liquid: viscous
Details on test material:
- Appearance: dark, high viscous liquid
- Storage Conditions: room temperature <25 °C in the dark, may be used under light
- Stability under storage conditions: stable

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain: CRL: CD (SD) BR SPF.
- Age at study initiation: Approximately 8 weeks (males) and 12 weeks (females) at the time of administration.
- Weight at study initiation: 270 to 284 g (males); 245 to 252 g (females).
- Fasting period before study: No.
- Housing: Single caging (39 cm x 23 cm x 18 cm cages) with wire mesh lids. Cages were sanitised once a week. Autoclaved aspen wood chips were used as bedding material; also changed weekly.
- Diet (e.g. ad libitum): gamma irradiated with 25 kGy ⁶⁰Co, ad libitum.
- Water (e.g. ad libitum): Tap water, from an automatic watering system, ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average of 22 °C (continuous control and recording).
- Humidity (%): Average of 67 %(continuous control and recording).
- Air changes (per hr): 12 per hour.
- Photoperiod (hrs dark / hrs light): Artificial light from 6 am to 6 pm.

IN-LIFE DATES: From: 9 August 2005 To: 25 August 2005

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: A single dermal administration was performed by spreading the test material on an area of 6.5 x 8 cm (52 cm²). The test site was located on the dorsal thoracal region. The hair of the dorsal trunk was clipped with an electrical hair clipper (Aesculap GH, 0.1 mm cutter head) one day prior to application.
- % coverage: At least 10 % of the estimated body surface.
- Type of wrap if used: A cellulose patch (Pehazell, Hartmann AG) with the calculated amount of the test material on the surface was applied to the test site and held in place by fixing marginally with non irritating tape (Blenderm Wundpflaster, 3M). Patch and tape were covered semi-occlusively by a dressing (Fixomull Stretch, Fa. Beiersdorf).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance was wiped off using wet cellulose tissue, if necessary, once the dressing, the tape and the patch were removed at the end of the eposure period.
- Time after start of exposure: At the end of the exposure period (24 hours).

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight; the amounts were calculated and weighed for each individual using the body weights determined on the day of the administration.
Duration of exposure:
24 hours.
Doses:
2000 mg/kg bodyweight.
No. of animals per sex per dose:
5 animals per sex per dose.
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Observations were performed at 0 to 0.5, > 0.5 to 1, > 1 to 2, > 2 to 4 and > 4 to 6 hours after administration and then at least once a day. Observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions. No skin examination of the administration site was possible during the exposure period, while it was covered by the patch and wrappings.
Body weights were determined before administration, 7 and 14 days after dosing. Body weight gain was calculated for each week of the study, between 0 and 7 days and 7 and 14 days after dosing.
- Necropsy of survivors performed: Yes. All animals were killed by inhalation of 80 % CO₂ + 20 % O₂ 14 days after dosing and subjected to a necropsy including a gross pathological examination.

- Justification for selection of the dose level: In a range finding study, three groups of one male and one female each were dosed with 400, 894 or 2000 mg/kg bodyweight. All animals survived for 7 days; therefore a limit-test with one dose of 2000 mg/kg body weight was performed. Both animals, dosed with 2000 mg/kg in the preliminary test were included into the main study.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality. All animals survived until the scheduled termination of the study.
Clinical signs:
All animals were normal during the entire observation period. Exposed skin was not found to be altered by the test material.
Body weight:
- Males: Bodyweights and bodyweight gain were unremarkable during the entire study in all males.
- Females: Bodyweight loss was noted in 1 female in the first week. This might be due to the discomfort caused by the dressing and was not considered to be toxicologically relevant. Bodyweights and bodyweight gain were inconspicuous in the second week in all females.
Gross pathology:
All animals were normal at terminal necropsy.
Other findings:
No noteworthy sex difference in the response to the test material was derived from clinical observations or post-mortem findings.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the LD50 was found to be >2000 mg/kg bw in male and female rats and therefore requires no classification in accordance with EU criteria.
Executive summary:

The potential of the test material to cause acute toxic effects when administered by the dermal route was investigated in accordance with the standardised guidelines OECD 402 and EU Method B.3 under GLP conditions.

The test material was administered once dermally on the dorsal thoracal region of 5 male and 5 female Sprague Dawley rats at a limit dose of 2000 mg/kg bw.

A cellulose patch with the individually weighed amount of the test material on the surface was applied to the test site and held in place by fixing marginally with non irritating tape. This was covered by a semi-occlusive dressing and left in place for 24 hours.

There was no mortality and no local or systemic effects related to administration of the test material. All animals appeared normal at necropsy.

Under the conditions of this study the LD50 was found to be >2000 mg/kg bw in male and female rats and therefore requires no classification in accordance with EU criteria.

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