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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 based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
February to March 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This is a GLP guideline study and is used in read-across from Alchisor CAL 123 (see 'Read Across Justification Document'). The study merits a Klimisch 1 rating; Klimisch 2 when used for read-across.

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)
Deviations:
yes
Remarks:
Temperature and humidity outside protocol range but did not affect study outcome
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
yes
Remarks:
see above
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study was conducted for other regulatory requirements.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Alkenes, C11-12, hydroformylation products, distn. residues, Alchisor CAL (Commercial Name)
- Substance type: pure active substance
- Physical state: colourless liquid
- Storage condition of test material: at room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Hdq: Wilmington, MA, USA
- Age at study initiation: approx. 5 weeks
- Weight at study initiation: 333 - 382 g (males); 345 - 405 g (females)
- Housing: 1 - 5 animals per cage, males separate from females (cage type: suspended, wire bottom, stainles steel); housed individually for 3 days during wrapping
- Diet: PMI Feeds, Inc. Guinea Pig Diet ad libitum
- Water: Municipal water ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24 (temperature outside protocol range)
- Humidity (%): 26-63 (humidity outside protocol range)
- Air changes (per hr): 10 - 12
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 2010-02-21 To: 2010-03-20

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
5 % v/v solution of test substance in vehicle with and without adjuvant (50:50 v/v) for intradermal injections; 100 % undiluted test substance for epicutaneous and challenge applications
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
5 % v/v solution of test substance in vehicle with and without adjuvant (50:50 v/v) for intradermal injections; 100 % undiluted test substance for epicutaneous and challenge applications
No. of animals per dose:
10 animals per sex for the test group, 5 per sex for the control group; 3 per sex for range finding
Details on study design:
RANGE FINDING TESTS:
Intradermal testing: 0.5, 1 , 2 and 5 % v/v in corn oil at 1 male and 1 female animal (left and right flanks); dose amount 0.1 mL; evaluation after 24 and 48 hours
Topical application: 25, 50, 75 and 100 % v/v at 2 male and 2 female animals (left and right flanks); dose amount 0.5 m; evaluation after 48 hours


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period:
Intradermal: single injections
Epicutaneous: 48 hours, evaluation 24 hours after patch removal
- Test groups:
Intradermal: 3 pairs of symmetrical intradermal injections (0.1 mL each). Injections sites 1&2: Freund's Complete Adjuvant - 50% v/v in saline; injection sites 3&4: test substance 5% (v/v) in corn oil; injection sites 5&6: Mixture (50:50) of Freund's Complete Adjuvant in saline and test substance in corn oil
Epicutaneous: 0.5 mL of 100% undiluted test substance
- Control group:
Intradermal: The control animals received the same injections as the test group animals with the vehicle substituted for the test substance in the second and third pairs of injections.
- Site:
Intradermal: on the upper back of each animal within a 4x6 cm exposure area running laterally across the shoulders, clipped free of hairs; injections sites 1&2: one on each side of the spinal column and approx. 3.5 cm apart; injection sites 3&4: approx. 0.5 cm behind the first pair of injections; injection sites 5&6: approx. 0.5 cm behind the second pair of injections; all injections were within a 2x4 cm area of the 4x6 cm exposure area
Epicutaneous: applied to the exposure area to cover the intradermal injection sites (a 25 mm glass fiber filter patch was used to cover the dose site, the patch was then occluded with an adhesive masking tape and secured in place with an elastic adhesive wrap)
- Frequency of applications: Intradermal injections at day 0, epicutaneous application on day 7
- Duration: 3 weeks
- Concentrations:
Intradermal: 5% (v/v) in corn oil
Epicutaneous: 100% undiluted test substance


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 21
- Exposure period: 24 hours
- Test groups: 0.5 mL test substance applied topically to the right flank; 0.5 mL of corn oil applied topically to the left flank (a 25 mm glass fiber filter patch was used to cover the dose sites, secured as in the induction exposure)
- Control group: same treatment as test group animals
- Concentrations: 100% undiluted test substance
- Evaluation (hr after challenge): 48 and 72 hours (24 and 48 hours after patch removal)
Challenge controls:
see above
Positive control substance(s):
yes
Remarks:
alpha-Hexylcinnamaldehyde 85%

Results and discussion

Positive control results:
The sensitivity of guinea pigs to a positive control material is confirmed in the laboratory periodically (In-life start: 10 Ma 10; In-life completed: 3 Apr 10).
All positive control animal exhibited discrete to moderate erythema after the challenge treatment (concentrations administered: 25% v/v solution of positive control substance in corn oil with and without adjuvant (50:50 v/v) for intradermal injections; undiluted positive control substance for topical and challenge applications). None of the animals of the naive control group exhibited erythema after the challenge treatment.
The positive control substance was considered an extreme sensitizer and confirmed the sensitivity of the used strain of guinea pigs.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
18
Clinical observations:
Two test animals died, deaths were not considered related to substance administration.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 18.0. Clinical observations: Two test animals died, deaths were not considered related to substance administration..
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
18
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 18.0.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
One control animal died.
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 9.0. Clinical observations: One control animal died..
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
9
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 9.0.

Any other information on results incl. tables

A pre-test screen with 3 animals/sex was conducted to determine induction concentrations producing no more than moderate irritation, and a maximum non-irritation challenge concentration. Based on screen results, a 5% v/v solution of test substance in corn oil was selected for intradermal injection, and 100% undiluted test substance was selected for the topical application (induction and challenge).

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
The challenge treatments with either vehicle alone or test substance in vehicle produced no erythema in any of the test and or control group animals. Body weight gain was unaffected by the administration of the test substance. Since none of the test animals exhibited scores greater than 0, the test substance Alcohols, C18-22, distn. residues was given a sensitization potency rating of non-sensitizing (Grade 0).
Executive summary:

A maximization test for topically applied test substances was conducted on 30 short-haired male and female albino guinea pigs using the methods of Magnusson and Kligman according to the OECD Guideline of the Testing of Chemicals No. 406 "Skin Sensitisation", adopted on 17th July 1992.

Test group animals (10/sex) received three pairs of intradermal injections (adjuvant, a solution of test substance in corn oil, and a 50:50 mixture of adjuvant and the test substance solution) followed one week later by a single topical application of the undiluted test substance. Ten additional animals (5/sex) served as a control group. Control animals were treated at the same time periods and locations but with the vehicle used in place of the test substance solution. Two weeks after the topical application, the test animals were challenged with a second topical application of the undiluted test substance at a virgin test site. Control animals were also given a topical application of undiluted test substance. The percentage of animals exhibiting erythema with or without edema after the challenge treatment was used to assign the test substance a sensitization potency rating. Since none of the test animals exhibited scores greater than 0, the test substance Alkenes, C11 -12, hydroformylation products, distn. residues was given a sensitization potency rating of non-sensitizer (Grade 0).

During the study, two test animals and one control animal died; deaths were not considered related to substance administration.