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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restrictions because it closely followed OECD 406 guidelines and was GLP compliant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1996

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Reference substance name:
Alkenes, C11/C13/C14
IUPAC Name:
Alkenes, C11/C13/C14
Details on test material:
- Name of test material (as cited in study report): SHOP C134 Internal Olefin
- Test substance: Alkenes, C11/C13/C14
- Physical state: Liquid (clear, colourless)
- Lot/batch No.: 134260
- Storage condition of test material: cool conditions (not exceeding 13 degrees C), under nitrogen, protected from light, in the original container

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall, Darley Oaks, Newchurch, Burton on Trent, Staffordshire, England
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation: 334 to 435 g
- Housing: Stainless steel cages, grid floors and tops. No more than five animals of the same sex were assigned to each cage. Cages were suspended in mobil stainless steel racks.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 21
- Humidity (%): 40 to 69
- Air changes (per hr): At least 10
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
propylene glycol
Concentration / amount:
First induction: 50% v/v SHOP C134 in propylene glycol, 50% v/v SHOP C134 in FCA (Freunds Complete Adjuvant)
Second induction: SHOP C134 as supplied
Challenge: 1% v/v SHOP C134 in propylene glycol, 0.3% v/v SHOP C134 in propylene glycol
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
First induction: 50% v/v SHOP C134 in propylene glycol, 50% v/v SHOP C134 in FCA (Freunds Complete Adjuvant)
Second induction: SHOP C134 as supplied
Challenge: 1% v/v SHOP C134 in propylene glycol, 0.3% v/v SHOP C134 in propylene glycol
No. of animals per dose:
First induction (intradermal):
- 10 control animals: received FCA, Vehicle, and Vehicle in FCA at 3 different injection sites
- 20 test animals: received FCA, test material in vehicle, and test material in FCA at 3 different injection sites
Second induction:
- 10 control animals: received topical application of vehicle
- 20 test animals: received topical application of test material as supplied
Challenge:
- 10 control animals received: vehicle, 1% v/v SHOP C134 in propylene glycol and 0.3% v/v SHOP C134 in propylene glycol at 3 different sites
- 20 test animals received: vehicle, 1% v/v SHOP C134 in propylene glycol and 0.3% v/v SHOP C134 in propylene glycol at 3 different sites
Details on study design:
RANGE FINDING TESTS: Primary skin irritation screen. Concentrations chosen for use in induction and challenge were to be well-tolerated locally and systemically. They were selected on the following criteria: intradermal injections were not to cause necrosis or ulceration of the skin, topical induction was to cause, at most, a weak or moderate inflammatory response and the concentration used at challenge was to be at the highest sub-irritant level. In the primary skin irritation screen, 4 guinea pigs were used in the intradermal administration, 2 guinea pigs were used in the topical induction, and 3 guinea pigs were used in the challenge administration.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 pairs of intradermal injections per animal, topical application for all animals (control: vehicle, test: test material as supplied)
- Exposure period: Day 1 received intradermal injections, Day 8 received topical application for 48 hours.
- Test groups: 20 animals (10 male/10 female)
- Control group: 10 animals (5 male/5 female)
- Site: Intradermal: closely clipped dorsa 3 pairs of injections deep into dermis on sides of dorsal median line. Topical: site overlying the scapulae
- Frequency of applications: intradermal: one, topical: one
- Duration: Day1-8 exposures
- Concentrations: First induction: 50% v/v SHOP C134 in propylene glycol, 50% v/v SHOP C134 in FCA (Freunds Complete Adjuvant)
Second induction: SHOP C134 as supplied.

B. CHALLENGE EXPOSURE
- No. of exposures: 3 test sites per animal
- Day(s) of challenge: On Day 22
- Exposure period: Occlusive, 24 hours
- Test groups: 20 animals (10 male/10 female)
- Control group: 10 animals (5 male/5 female)
- Site: vehicle on left flank, challenge doses on two sites of right flank
- Concentrations: Vehicle, 1% v/v SHOP C134 in vehicle, 0.3% v/v SHOP C134 in vehicle
- Evaluation (hr after challenge): 24 and 48 hours after dressing removal
Challenge controls:
Equivalent challenge dosing as test animals
Positive control substance(s):
no

Results and discussion

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
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.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
10
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.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
20
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.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
20
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.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1% v/v SHOP C134 in vehicle
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1% v/v SHOP C134 in vehicle. No with. + reactions: 2.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1% v/v SHOP C134 in vehicle
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1% v/v SHOP C134 in vehicle. No with. + reactions: 3.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1% v/v SHOP C134 in vehicle
No. with + reactions:
6
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1% v/v SHOP C134 in vehicle. No with. + reactions: 6.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1% v/v SHOP C134 in vehicle
No. with + reactions:
4
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1% v/v SHOP C134 in vehicle. No with. + reactions: 4.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.3% v/v SHOP C134 in vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.3% v/v SHOP C134 in vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.3% v/v SHOP C134 in vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.3% v/v SHOP C134 in vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.3% v/v SHOP C134 in vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.3% v/v SHOP C134 in vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.3% v/v SHOP C134 in vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.3% v/v SHOP C134 in vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

Intradermal injection of 50% v/v SHOP C134 in propylene glycol gave rise to slight or moderate erythema and discolouration; a similar administration of 50% v/v SHOP C134 in FCA casued moderate erythema, discolouration and occasional pallor. Occluded topical induction application of SHOP C134 as supplied gave rise to exfoliation and loss of flexibility.

Challenge application of 1% v/v SHOP C134 in propylene glycol gave rise to eschar formation in 3 test and 3 control animals and slight erythema in further 3 test animals. Fifteen test and 5 control animals showed exfoliation. Challenge application of 0.3% v/v SHOP C134 in propylene glycol gave rise to exfoliation in 3 test and the only reaction to treatment. Challenge application of propylene glycol alone gave rise to exfoliation in 2 animals; no other dermal reaction was evident.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of this study, repeated applications of SHOP C134 did not cause delayed contact hypersensitivity in the guinea-pig.
Executive summary:

In a dermal sensitization study using SHOP C134 in propylene glycol, albino guinea-pigs of the Dunkin-Hartley strain (10 male/10 female) were tested by the Magnusson-Kligman Maximisation Test. Twenty guinea pigs (10 male; 10 female) received an intradermal injection of 50% SHOP C134 in propylene glycol. Seven days later the animals were dermally treated in the same area with 100% SHOP C134 (as supplied) and the site was covered with an occlusive dressing for 48 hours. A challenge dose of either 1% or 0.3% SHOP C134 in propylene glycol was dermally administered on day 22, again with occlusive dressing. Test sites were then assessed 24 and 48 hours later. 

 

The intradermal injection of 50% SHOP C134 in propylene glycol caused slight to moderate erythema and discoloration. Undiluted SHOP C134 applied dermally caused exfoliation and loss of flexibility. After the challenge dose, 3 of 10 controls and 6 of 20 test animals treated with 1% SHOP C134 had slight erythema. There were no reactions after challenge with 0.3% SHOP C134 or propylene glycol. Under the conditions of this study, repeated applications of SHOP C134 did not cause delayed contact hypersensitivity in the guinea-pig.

 

This study received a Klimisch score of 1 and is classified asreliable without restrictions because it closely followed OECD 406 guidelines and was GLP compliant.