Registration Dossier

Administrative data

Description of key information

No acute toxicity data are available for Distilled Tall Oil. Good quality, guideline studies for the related substance Crude Tall Oil are therefore read across.

The key acute oral toxicity study gave an LD50 (oral) >2000 mg/kg bw (OECD 423, acute toxic class method) in rats (ARC, 2005a). There were no clinical signs or necropsy findings.


The key acute dermal toxicity study gave an LD50 (dermal) >2000 mg/kg bw (OECD 402, limit test) in rats (ARC, 2005b). There were no clinical signs, signs of local irritation or necrospy findings.

These values are read across to the registered substance, Distilled Tall Oil.


Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17.07.05 to 03.11.05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP,, using a closely-related test substance.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: Crl:CD(SD)IGS BR
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Age at study initiation: 8 weeks
- Weight at study initiation: 174-194 g
- Fasting period before study: Feed was withdrawn the evening before administration until three hours after administration.
- Housing: Individually caged in Makrolon cages type III
- Diet (e.g. ad libitum): Ad libitum (except during fasting)
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 (average)
- Humidity (%): 70.6 (average)
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 17-08-05 To: 07-09-05
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: No data
- Amount of vehicle (if gavage): Total of 10 ml/kg bw used
- Justification for choice of vehicle: The test substance was not soluble in water, and corn oil is a common vehicle for acute oral toxicity testing.
- Lot/batch no. (if required): No data
- Purity: No data


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As no prior information on the toxicity of the test substance was available, a starting dose of 300 mg/kg bw was chosen.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
Three
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed within the periods 0-0.5, 0.5-1, 1-2, 2-4 and 4-6 hours after administration of the test substance and then at least once per day up to two weeks. Body weights were determined before administration and 7 and 14 days after administration.
- Necropsy of survivors performed: yes
Statistics:
None
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No animals died
Mortality:
All animals survived until the scheduled termination of the study.
Clinical signs:
There were no clinical signs of toxicity.
Body weight:
All animals gained weight as expected.
Gross pathology:
There were no findings during the gross pathological examination.
Other findings:
No other findings.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
In a good quality acute oral toxicity study (reliability score 1) conducted to OECD test guideline 423, and GLP, the LD50 for Crude Tall Oil, whose chemical composition is similar to that of Distilled Tall Oil, was greater than 2000 mg/kg bw in Crl:CD(SD)IGS BR rats. It can therefore be concluded that the acute oral LD50 for Distilled Tall Oil is also >2000 mg/kg.
Executive summary:

Crude Tall Oil was administered once as a solution in corn oil (10 ml/kg bw), given orally via gavage to female Crl:CD(SD)IGS BR rats. The dosing was performed sequentially to groups of three animals per step using a starting dose of 300 mg/kg bw and 2000 mg/kg bw as the second dose. The animals were then observed for 14 days. Clinical observations were noted at least once per day, body weights were recorded before administration, and on days 7 and 14. At the end of the observation period all animals were sacrificed and necropsied. There were no clinical signs of toxicity, no deaths and all animals gained weight normally. The oral LD50 was therefore greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09.08.05 to 12.10.05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP, using a closely-related test substance.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CRL: CD(SD)BR SPF
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland
- Age at study initiation: Males: 8 weeks. Females: 12 weeks.
- Weight at study initiation: Males: 270 - 284 g. Females: 245 - 252g.
- Fasting period before study: No
- Housing: Individually in Makrolon cages Type III
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 (average)
- Humidity (%): 67 (average)
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 09.08.05 To: 25.08.05
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 52 cm2
- % coverage: 10% of estimated body surface.
- Type of wrap if used: Cellulose patch was held in place by a non-irritating tape. The patch and tape were covered semi-occlusively by a dressing.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with wet cellulose tissue.
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Five
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed 0-0.5, 0.5-1, 1-2, 2-4 and 4-6 hours after administration of the test substance and then at least once per day for two weeks. Body weights were recorded before administration and on Days 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
None
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: No deaths occurred
Mortality:
All animals survived until scheduled termination of the study.
Clinical signs:
There were no clinical signs of toxicity.
Body weight:
Body weight loss was noted in 1/5 females in the first week. The authors concluded that this might have been caused by the discomfort of the dressing and was not considered to be toxicologically significant. Body weights and body weight gains were normal in the second week. There were no effects on male body weights.
Gross pathology:
There were no abnormal findings during the gross pathological examination.
Other findings:
No other findings.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
In a good quality acute dermal toxicity study (reliability score 1) conducted to OECD test guideline 402, and GLP, the LD50 for Crude Tall Oil , which has a chemical composition similar to that of Distilled Tall Oil, was greater than 2000 mg/kg bw in Crl:CD(SD)IGS BR rats. It can therefore be concluded that the acute dermal LD50 of Distilled Tall Oil is also >2000 mg/kg.
Executive summary:

A single dermal administration of Crude Tall Oil was performed, by spreading the test substance on an area of skin that was at least 10% of the estimated body surface of male and female CRL: CD(SD)BR SPF rats. 2000 mg/kg bw of the test substance was held in place with a semi-occlusive dressing for 24 hours. At the end of the exposure period the residual test substance was wiped off with a wet cellulose tissue, when necessary. The animals were then observed for 14 days. Clinical observations were noted at least once per day, body weights were recorded before administration, and on days 7 and 14. At the end of the observation period all animals were sacrificed and necropsied. There were no clinical signs of toxicity, no deaths and there were no treatment-related effects on body weight. The dermal LD50 was therefore greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

There is no acute toxicity data are available for Distilled Tall Oil. Acute oral and dermal toxicity studies are, however, available for the related substance Crude Tall Oil.Read-across of acute toxicity data from CTO to DTO is justified on the grounds that all the chemical constituents that are present in DTO are present in CTO i.e. fatty acids, resin acids, polymers and neutral compounds containing alcohols, hydrocarbons etc. It should be noted that Distilled Tall Oil contains a higher proportion of non-hazardous fatty acids that are exempt from REACH in accordance with Annex V of the Regulation. In addition, the chemical constituent blocks of which they are comprised are compositionally very similar and are made up of constituents with common functional groups and properties. As a result the substances share very similar physicochemical properties both in terms of their bulk properties and the properties of the constituent blocks. CTO does contain some constituents that are not present in DTO and for this reason read-across from DTO to CTO is not considered appropriate. However, for the purposes of read-across from CTO to DTO this is only likely to make the outcome conservative i.e. if anything the hazard of DTO is likely to be overestimated. A more detailed description of the technical justification for read-across is given in Section 1.4 of the CSR.

Acute oral toxicity:

Three acute oral toxicity studies are available for Crude Tall Oil. In all cases, the observed LD50 was greater than 2000 mg/kg bw. The key study was selected as the most recent study which was conducted in accordance with OECD Test Guideline 423 and in compliance with GLP.

Acute dermal toxicity:

An acute dermal toxicity study is available for Crude Tall Oil. The test was carried out in accordance with OECD Test Guideline 402 (limit test) and in compliance with GLP. The observed LD50 was greater than 2000 mg/kg bw.

Acute Inhalation Toxicity:

No acute inhalation studies in animals are available for Distilled Tall Oil. Testing is not required since a reliable acute dermal study is available for a related substance, and inhalation exposure is not expected for this very low volatility substance. 

Justification for classification or non-classification

According to the criteria in Regulation 1272/2008, Distilled Tall Oil is not classified for acute toxicity based on read-across from Crude Tall Oil, for which LD50 values for oral and dermal toxicity were greater than 2000 mg/kg bw.