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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
08 Oct 1998 - 26 Nov 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP Guideline study Read-Across justification for CAS No. 61790-12-3: On the basis of Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby human health effects may be predicted from data for a reference substance, provided that the physicochemical, toxicological and ecotoxicological properties of the reference and target substances are likely to be similar as a result of structural similarity, read-across from the surrogate substance fatty acids, tall-oil (CAS No. 61790-12-3) is conducted and the aforementioned study is selected as a key study for assessment of potential skin sensitising effects of the members of the category Dimerised Fatty Acids and its Derivates. The similarities between fatty acids, tall-oil and the category members are based on the following considerations: The Dimerised Fatty Acids and its Derivates category includes the following members: 61788-89-4 Fatty acids, C18-unsaturated, dimers, “Dimer” 68937-90-6 Fatty acids, C18-unsaturated, trimers, “Trimer” 68783-41-5 Fatty acids, C18-unsaturated, dimers, hydrogenated, “Hydrogenated dimer” 71808-39-4 Fatty acids, C16-18 and C18 unsaturated, dimerized, “Crude dimer” 68955-98-6 Fatty acids, C16-18 and C18-unsaturated, branched and linear, “Monomer acid” 68201-37-6 Octadecanoic acid, branched and linear, “Hydrogenated monomer acid” 30399-84-9 Isooctadecanoic acid All the members of this category of substances are derived from unsaturated fatty acids, for example from fatty acids, tall-oil, which contains predominantly C18 unsaturated and saturated fatty acids. Natural fatty acids, tall-oil has the following properties: Chemical name: Fatty acids, tall-oil Chemical formula: not available - UVCB substance EC No.: 263-107-3 CAS Name: Fatty acids, tall-oil CAS number: 61790-12-3 logKow: determined range 4.9 – 7.6 (Lightbody et al., 2002) Solubility in water (mg/L, at 20 °C): 12.6 (The quoted value represents the sum solubility of all the components of the test material) (Dinwoodie, 2004) Biodegradation at 28 days: 56-84% (Madsen, 1993; Aniol, 1999; Sewell, 1994) The HPV report final submission for fatty acids, tall-oil and related substances; CAS No. 61790-12-3 CAS No. 65997-03-7 CAS No. 68955-98-6 CAS No. 68201-37-6 CAS No. 61790-44-1 CAS No. 61790-45-2 Submitted to the US EPA August 2004 was screened by the US EPA and a screening level hazard characterisation report was published in 2007 (U. S. Environmental Protection Agency, 2007). This report prepared by the High Production Volume Chemicals Branch indicated that fatty acids, tall-oil are non-toxic following acute oral exposure (LD50 (rat) > 10000 mg/kg bw) and following a 90-day test in rats the No Observed Effect Level (NOEL) was 5% (approximately 2500 mg/kg bw/day). Fatty acids, tall-oil were negative in an Ames test with 5 S. typhimurium strains and in an in vitro chromosomal aberration assay with Chinese Hamster Ovary cells. In a Two-Generation Reproduction Toxicity study in rats, the NOEL for reproduction and systemic toxicity was 10% in diet (ca. 5000 mg/kg bw/day). Furthermore, fatty acids, tall-oil were not acute toxic in fish (96 h NOELr 1000 mg/L), daphnia (48 h NOELr 1000 mg/L) and algae (72 h NOELr 845 mg/L). Given their chemical nature, fatty acids, tall-oil are expected to be absorbed, metabolised and excreted following the same well-known pathways of dietary fatty acids. In conclusion, the physicochemical, toxicological and ecotoxicological properties of fatty acids, tall-oil and the members of the category Dimerised Fatty Acids and its Derivates are considered to be similar, and similarity is based on common functional groups (long-chain fatty acids, saturated and unsaturated) and the likelihood of common breakdown products via the metabolism of fatty acids. It is therefore considered appropriate that the skin sensitisation data of fatty acids, tall-oil is used for read-across purposes to this category. The selected study fulfils the requirements laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 for read-across, i.e. the results are adequate for the purpose of classification and labelling and/or risk assessment; have adequate and reliable coverage of the key parameters addressed in the corresponding test method referred to in Article 13(3); cover an exposure duration comparable to or longer than the corresponding test method referred to in Article 13(3); and adequate and reliable documentation of the applied method is provided.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Remarks:
Scantox
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tall Oil Fatty Acid
- Physical state: light yellow liquid
- Analytical purity: no data
- Storage condition of test material: at room temperature in the dark

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: M & B, Ejby, Lille Skensved, Denmark
- Weight at study initiation: 277-337 g
- Housing: Two or three to a cage (macrolone type IV)
- Diet (e.g. ad libitum): Pelleted diet ("Altromin 3113" from Chr. Petersen A/S, Ringsted, Denmark) ad libitum. Autoclaved hay 3 times a week.
- Water (e.g. ad libitum): domestic quality drinking water (enriched with vitaminC and acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth) ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
coconut oil
Concentration / amount:
6.25% w/w for intradermal induction
25% w/w for topical induction
12.5% w/w for challenge
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
coconut oil
Concentration / amount:
6.25% w/w for intradermal induction
25% w/w for topical induction
12.5% w/w for challenge
No. of animals per dose:
Vehicle: 10
Test article: 20
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Test groups: Test material in coconut oil
- Control group: coconut oil
- Site: Shoulder region
- Frequency of applications: Days 1 (intradermal) and 8 (topical)
- Duration: 48 h (topical application)
- Concentrations: 6.25% w/w


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21
- Test groups: Test material in coconut oil
- Control group: Test material in coconut oil
- Site: Left flank
- Concentrations: 12.5% w/w
- Evaluation (hr after challenge): 24 and 48 h (Days 23 and 24)
Positive control substance(s):
yes
Remarks:
Hexyl cinnamic aldehyde, 12.5% w/w in ethanol/diethylphthalate 1:1

Results and discussion

Positive control results:
Under experimental conditions similar to those described for the main study, evidence of delayed contact hypersensitivity was seen in 6 out if 10 animals (60%).

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
12.5% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 12.5% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no effects.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
12.5% w/w
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 12.5% w/w. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
12.5% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 12.5% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
12.5% w/w
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 12.5% w/w. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no effects.

Any other information on results incl. tables

None of the animals showed signs of ill health.

The animals had a normal body weight gain during the study period.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the experimental conditions described, It was concluded that no evidence of delayed contact hypersensitivity reaction was seen after treatment with the test material.