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Diss Factsheets

Administrative data

Description of key information

The hazard information on the substance is based on read across from Tall oil and 2-ethylhexanoic acid and reveals low toxicity, however may irritate the skin. Furthermore, the source substances contain higher or similar concentrations of the constituents used for read across compared to the target substance. There are no scientific reasons indicating that the constituents of the substance can interact in a way that will influence the toxicological/ecotoxicological properties of the substance.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2005-09-13 - 2005-09-19
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Justification for read across, see attached document.
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
24 april 2002
GLP compliance:
yes (incl. QA statement)
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA/Ca
Remarks:
CBA/CaOlaHsd
Sex:
female
No. of animals per dose:
5
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
A (low dose) 10 % Crude Tall Oil (v/v) 15 mg
B (mid dose) 25 % Crude Tall Oil (v/v) 37.5 mg
C (high dose) 50 % Crude Tall Oil (v/v) 75 mg
K (negative control) AOO 150 mg
P (positive control) 25% HCA in AOO (v/v) 37.5 mg
No. of animals per dose:
5
Details on study design:
The test substance was administered in 3 concentrations to the dorsal surfaces of the ears of the animals of the test substance groups. In a manner identical to that of animals in the treatment groups animals of one negative control group and one positive control group were treated with AOO and HCA respectively. Each animal was treated for 3 consecutive days. 3 days after the last administration the proliferation of the lymphocytes of the draining lymph nodes was measured by the determination of the amounts of incorporated 3HTdR.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Positive control results:
The positive control substance led to a stimulation index of 5.3.
Key result
Parameter:
SI
Value:
0.9
Test group / Remarks:
Low dose dpm 4338
Key result
Parameter:
SI
Value:
2.6
Test group / Remarks:
mid dose dpm 13098
Key result
Parameter:
SI
Value:
3.9
Test group / Remarks:
High dose dpm 19314
Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Remarks:
According to the OECD-Guideline 429 and the Directive 2004/73/EC, method B.42., "Skin Sensitisation: Local Lymph Node Assay", "Crude Tall Oil" is regarded as a sensitiser in the LLNA.
Conclusions:
3H-thymidine incorporation, stimulation indices The calculated stimulation indices (test substance/negative control ratio) were decisive for the grading of the potential of sensitisation: According to the guidelines the decision process with regard to a positive response includes a stimulation index of equal to or greater than 3, together with consideration of dose-response.  

A concentration related response was observed. The SIs of the tested test substance concentrations were 0.9 (low dose), 2.6 (mid dose) and 3.9 (high dose).

Positive control The positive control substance led to a stimulation index of 5.3, thus demonstrating the validity of the experiment.
Executive summary:

Aim  

The Local Lymph Node Assay was performed to evaluate a possible skin sensitising potential of  "Crude Tall Oil" according to the OECD-Guideline 429, 24 April 2002 and the EC Directive 2004/73/EC, method B.42., 30 April 2004.

Method

The test substance was diluted with Acetone:olive oil, 4:1, v/v (AOO) and was administered to three groups of 5 female CBA/Ca mice. Administration was performed epicutaneously to the dorsal surface of both ears, once a day on three consecutive days. The volume administered was 25 µL per ear.

Concentrations used:  

• Group A (low dose):  10% (v/v) solution of "Crude Tall Oil" in AOO

• Group B (mid dose):  25% (v/v) solution of "Crude Tall Oil" in AOO

• Group C (high dose):  50% (v/v) solution of "Crude Tall Oil" in AOO

Two groups with 5 animals each served as positive and negative controls. Both control substances were administered under identical conditions as the test substances.  The following solutions served as control substances:

• Group P (positive control): 25% (v/v) solution of hexyl cinnamic aldehyde in acetone:olive oil (4:1, v/v)

• Group K (negative control): AOO

5 days after the first topical application, 3H-thymidine was intravenously administered to all mice via a tail vein. Approximately 5 hours later all animals were sacrificed, the draining auricular lymph nodes were excised, pooled for each group, and single cell suspensions were prepared. Then incorporation of 3H-methyl thymidine into the cells was determined (liquid scintillation counter) and compared with the negative controls. The stimulation index (SI) was calculated as the ratio of the disintegrations per minute (dpm) of the dosed groups or of the positive control group to the dpm of the negative control group.

Results

General All animals survived till the end of the study.  No adverse effects were noted in any animal.  Body masses and body mass gains were in the range to be expected from animals of the same strain, sex and age. No skin irritating effects were observed in the test substance groups and both control groups throughout the whole study.  

3H-thymidine incorporation, stimulation indices The calculated stimulation indices (test substance/negative control ratio) were decisive for the grading of the potential of sensitisation: According to the guidelines the decision process with regard to a positive response includes a stimulation index of equal to or greater than 3, together with consideration of dose-response.  

A concentration related response was observed. The SIs of the tested test substance concentrations were 0.9 (low dose), 2.6 (mid dose) and 3.9 (high dose).

Positive control The positive control substance led to a stimulation index of 5.3, thus demonstrating the validity of the experiment.

CONCLUSION

According to the OECD-Guideline 429 and the Directive 2004/73/EC, method B.42., "Skin Sensitisation: Local Lymph Node Assay", "Crude Tall Oil" is regarded as a sensitiser in the LLNA.

According to the results of this study and to the Directive 2001/59/EC for classification, the test substance "Crude Tall Oil" needs to be labelled with "R43  May cause sensitisation by skin contact".  

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP; non guideline; minor restrictions in design but adequate for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
GPMT test already available since 1979
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Route:
intradermal and epicutaneous
Vehicle:
water
Route:
epicutaneous, occlusive
Vehicle:
water
No. of animals per dose:
treated group: 10
control group: 5
Details on study design:
RANGE FINDING TESTS: 2 guinea pigs which were pre-treated with adjuvant only at the induction phase, test substance was applied at concentrations of 10, 5, 2 and 1%. A concentration of 2% was selected as the level to be used at the challenge stage.

MAIN STUDY
A. INDUCTION EXPOSURE
treated group: 3 injections: a) 0.1 ml Freund's adjuvant alone; b) 0.1 ml 2-ethylhexoic acid (1% w/w) alone; c) 0.05 ml 2-ethylhexoic acid (1% w/w) emulsified with 0.05 ml Freund's adjuvant; 6 days after the injection phase: treatment with sodium lauryl sulphate solution (10 % w/w), after 24 h: patch of Whatman No. 3 MM filter paper saturated with 2-ethylhexoic acid (5% w/w) covered by an overlapping patch of impermeable plastlc adhesive tape for48 h
control group: injection with Freund's adjuvant alone

B. CHALLENGE EXPOSURE
treated and control group: two weeks after the topical induction: 2-ethylhexoic acid (2% w/w) was applied on a 2 x 2 cm piece of filter paper to the test site of the guinea pig. The patch was held in place for the topical induction and removed 24 h Iater.

The degree of response was determined by trained assessors 24 h after removal of the challenge patch. Positive response are rated
according to the percentage of animals sensitised (Kligman).
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no data.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
2% w/w
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 2% w/w. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no data.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions tested, the test substance is a non-sensitiser in guinea pigs.
Endpoint:
skin sensitisation, other
Remarks:
LLNA and non-LLNA
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See attached file for justification of read across
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2 % w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no data
Remarks on result:
other: 2-EHA
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
2 % w/w
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no data
Remarks on result:
other: 2-EHA
Key result
Parameter:
SI
Variability:
0.9-3.9
Remarks on result:
other: tall oil
Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

There is no reason to believe that results obtained in the studies would not be applicable to humans.

Justification for selection of skin sensitisation endpoint: OECD & EC guideline study, no deviations, GLP

Justification for classification or non-classification

"Crude Tall Oil"  is regarded as a sensitiser in the LLNA according to the OECD-Guideline 429 and the Directive 2004/73/EC, method B.42., "Skin Sensitisation: Local Lymph Node Assay", since the SIs of one examined test substance concentrations was greater than 3.  According to the results of this study and to the Directive 2001/59/EC for classification, the test substance "Crude Tall Oil" needs to be labelled with "H317  May cause sensitisation by skin contact". Because of the classification of crude tall oil, the substance is classified as skin sensitising category 1 and needs to be labelled with "H317  May cause sensitisation by skin contact". The available data is not sufficient for sub classification into skin sensitising 1A or 1B. However, 2-ethylhexanoic acid is not regarded a sensitizer in the non-LLNA test.