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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
For unsaturated compounds that bear structural similarity to the test substance, GPMT may give results that more adequately reflects the relevance for humans (see Comparison of the skin sensitizing potential of unsaturated compounds as assessed by the murine local lymph node assay (LLNA) and the guinea pig maximization test (GPMT) - R. Kreiling, H.M. Hollnagel, L. Hareng, D. Eigler, M.S. Lee, P. Giem, B. DreeBen, M. Kleber, A. Albrecht, C. Garcia, A. Wendel - Food and Chemical Toxicology 46 (2008) 1896-1904)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name: Fatty acids, tall-oil, reaction products with diethylenetriamine, maleic anhydride, tetraethylenepentamine and triethylenetetramine
CAS No.: 68990-47-6
Batch No.: TEE3316/22
Expiry Date: November 2011
Physical State at RT: solid
Colour: dark
Purity: 97%; Date of analysis: 11 Feb. 2010
Storage Conditions: at room temperature, protected from light
Solubility in Water: very low
Safety precautions: Routine hygienic procedures will be sufficient to assure personnel health and safety.

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 5 weeks old
- Weight at study initiation: 328 - 365 g
- Diet : Free access to autoclaved hay and to Altromin 3122 maintenance diet
- Water : Free access to tap water (drinking water, municipal residue control, microbiological control at regular intervals)
- Acclimation period: (at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): at least 10 x / hour
- Photoperiod (hrs dark / hrs light): Artificial light, sequence being 12 hours light, 12 hours dark

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
cotton seed oil
Concentration / amount:
For the intradermal injection (induction - first stage), 0.3591 g of the test item were suspended in 7.182 mL of vehicle to gain a 5% suspension (w/v). The test item was heated up to 80°C in an ultrasonic bath before being suspended in the vehicle.
For the topical application (induction – second stage), 2.64 mL of the test item were suspended in/with 2.64 g of vehicle to gain a 50% suspension (v/w). The test item was heated up to 80°C in an ultrasonic bath before being suspended in the vehicle.
For the topical application (challenge), 2.7125 g of the test item were suspended ad 10.85 mL of the vehicle to gain a 25% suspension (w/v). The test item was heated up to 80°C in an ultrasonic bath before being suspended in the vehicle.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
cotton seed oil
Concentration / amount:
For the intradermal injection (induction - first stage), 0.3591 g of the test item were suspended in 7.182 mL of vehicle to gain a 5% suspension (w/v). The test item was heated up to 80°C in an ultrasonic bath before being suspended in the vehicle.
For the topical application (induction – second stage), 2.64 mL of the test item were suspended in/with 2.64 g of vehicle to gain a 50% suspension (v/w). The test item was heated up to 80°C in an ultrasonic bath before being suspended in the vehicle.
For the topical application (challenge), 2.7125 g of the test item were suspended ad 10.85 mL of the vehicle to gain a 25% suspension (w/v). The test item was heated up to 80°C in an ultrasonic bath before being suspended in the vehicle.
No. of animals per dose:
Number of animals in the test group: 10
Number of animals in the negative control group: 5
Number of animals in the dose range finding study: 3

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: Intradermal Induction I, Injection site 1
Hours after challenge:
24
Group:
test group
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
erythema grade 1, oedema grade 1
Remarks on result:
other: Reading: other: Intradermal Induction I, Injection site 1. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: erythema grade 1, oedema grade 1.
Reading:
other: Intradermal Induction I, Injection site 1
Hours after challenge:
24
Group:
negative control
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
erythema grade 1, oedema grade 1
Remarks on result:
other: Reading: other: Intradermal Induction I, Injection site 1. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 5.0. Total no. in groups: 5.0. Clinical observations: erythema grade 1, oedema grade 1.
Reading:
other: Intradermal Induction I, Injection site 2
Hours after challenge:
24
Group:
test group
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
erythema grade 1, oedema grade 1
Remarks on result:
other: Reading: other: Intradermal Induction I, Injection site 2. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: erythema grade 1, oedema grade 1.
Reading:
other: Intradermal Induction I, Injection site 2
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
erythema grade 1, oedema grade 1
Remarks on result:
other: Reading: other: Intradermal Induction I, Injection site 2. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: erythema grade 1, oedema grade 1.
Reading:
other: Intradermal Induction I, Injection site 3
Hours after challenge:
24
Group:
negative control
No. with + reactions:
3
Total no. in group:
5
Clinical observations:
erythema grade 1
Remarks on result:
other: Reading: other: Intradermal Induction I, Injection site 3. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 3.0. Total no. in groups: 5.0. Clinical observations: erythema grade 1.
Reading:
other: Intradermal Induction I, Injection site 3
Hours after challenge:
24
Group:
test group
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
erythema grade 1, oedema grade 1
Remarks on result:
other: Reading: other: Intradermal Induction I, Injection site 3. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: erythema grade 1, oedema grade 1.
Reading:
other: Intradermal Induction I, Injection site 3
Hours after challenge:
24
Group:
negative control
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
oedema grade 1
Remarks on result:
other: Reading: other: Intradermal Induction I, Injection site 3. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 5.0. Total no. in groups: 5.0. Clinical observations: oedema grade 1.
Reading:
other: Intradermal Induction I, Injection site 1
Hours after challenge:
48
Group:
negative control
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
erythema grade 1, oedema grade 1
Remarks on result:
other: Reading: other: Intradermal Induction I, Injection site 1. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 5.0. Total no. in groups: 5.0. Clinical observations: erythema grade 1, oedema grade 1.
Reading:
other: Intradermal Induction I, Injection site 1
Hours after challenge:
48
Group:
test group
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
erythema grade 1, oedema grade 1, eschar
Remarks on result:
other: Reading: other: Intradermal Induction I, Injection site 1. . Hours after challenge: 48.0. Group: test group. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: erythema grade 1, oedema grade 1, eschar.
Reading:
other: Intradermal Induction I, Injection site 1
Hours after challenge:
48
Group:
negative control
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
eschar
Remarks on result:
other: Reading: other: Intradermal Induction I, Injection site 1. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 1.0. Total no. in groups: 5.0. Clinical observations: eschar.
Reading:
other: Intradermal Induction I, Injection site 2
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
erythema grade 1, oedema grade 1
Remarks on result:
other: Reading: other: Intradermal Induction I, Injection site 2. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: erythema grade 1, oedema grade 1.
Reading:
other: Intradermal Induction I, Injection site 2
Hours after challenge:
48
Group:
test group
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
erythema grade 1, oedema grade 1
Remarks on result:
other: Reading: other: Intradermal Induction I, Injection site 2. . Hours after challenge: 48.0. Group: test group. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: erythema grade 1, oedema grade 1.
Reading:
other: Intradermal Induction I, Injection site 3
Hours after challenge:
48
Group:
negative control
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
erythema grade 1, oedema grade 1
Remarks on result:
other: Reading: other: Intradermal Induction I, Injection site 3. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 5.0. Total no. in groups: 5.0. Clinical observations: erythema grade 1, oedema grade 1.
Reading:
other: Intradermal Induction I, Injection site 3
Hours after challenge:
48
Group:
test group
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
erythema grade 1, oedema grade 1
Remarks on result:
other: Reading: other: Intradermal Induction I, Injection site 3. . Hours after challenge: 48.0. Group: test group. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: erythema grade 1, oedema grade 1.
Reading:
other: dermal induction II
Hours after challenge:
24
Group:
test group
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
eschar
Remarks on result:
other: Reading: other: dermal induction II. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 4.0. Total no. in groups: 10.0. Clinical observations: eschar.
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
sensitisation
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: sensitisation.
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
sensitisation
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: sensitisation.

Any other information on results incl. tables

Main Test

Signs of irritation during the induction:

Intradermal Induction I (24 hours reading):

Injection site 1: erythema grade 1 in 5/5 control- and 10/10 test animals oedema grade 1 in 5/5 control- and 10/10 test animals Injection site 2: erythema grade 1 in 0/5 control- and 10/10 test animals oedema grade 1 in 0/5 control- and 10/10 test animals Injection site 3: erythema grade 1 in 3/5 control- and 10/10 test animals oedema grade 1 in 5/5 control- and 10/10 test animals Intradermal Induction I (48 hours reading):

Injection site 1: erythema grade 1 in 5/5 control- and 10/10 test animals oedema grade 1 in 5/5 control- and 10/10 test animals eschar in 1/5 control- and 10/10 test animals

Injection site 2: erythema grade 1 in 0/5 control- and 10/10 test animals oedema grade 1 in 0/5 control- and 10/10 test animals Injection site 3: erythema grade 1 in 5/5 control- and 10/10 test animals oedema grade 1 in 5/5 control- and 10/10 test animals

Dermal Induction II (48 hours exposure, occlusive):

Immediately after removing the patch: no effects observed

24 hours after removing the patch: eschar in 0/5 control- and 4/10 test animals.

Challenge Exposure (24 hours exposure, occlusive):

Erythema and oedema were observed during the observation period.

There was evidence of sensitisation and the percentage of animals sensitised was 90%.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of the present study it can be stated that the test item Fatty acids, tall-oil, reaction products with diethylenetriamine, maleic anhydride, tetraethylenepentamine and triethylenetetramine caused reactions identified as sensitisation at the tested concentration.