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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1998-06-09 to 1998-07-09 (application period of the main test)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Test substance consists of D and L isomers of panthenol.
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted July 17, 1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
1996
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Version / remarks:
revised November 1984
Deviations:
no
Principles of method if other than guideline:
The study is performed based on the method of BUEHLER EV (1965): Delayed Contact Hypersensitivity in the Guinea Pigs. Arch Dermat 91: 171-177.
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The study was performed before the LLNA test was available
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
female Pirbright White, Dunkin Hartley Crl:(HA)BR [SPF] guinea pigs
- Source: Charles River GmbH, Sulzfeld, Germany
- Age at study initiation: young adult animals, no further data
- Weight at study initiation: 323 - 374 g
- Housing: 5 animals per cage, in stainless steel wire mesh cages with plastic-coated grating, floor area 40 cm x 51 cm
- Diet: Kliba Laboratory Diet (Rabbit- Guinea Pig Maintenance Diet; Supplier: Klingentalmühle AG, Kaiseraugst, Switzerland), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 25 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
undiluted
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
undiluted
No. of animals per dose:
20 animals (test group)
10 animals (control groups)
Details on study design:
RANGE FINDING TESTS:
The pretest was performed with 4 female animals.
The test substance was applied to four clipped sites of the flanks of each animal for 2 x 6 hours under an occlusive dressing. Each animal was applied the undiluted test substance as well as solutions of the test substance in bidistilled water at concentrations of 75%, 50%, and 25%, each. The test material was applied 2 times (one application per week) on the same application area, respectively. The skin was read at 6 and 30 hours after beginning of application.
No signs of skin irritation were noted in any animal with any concentration at any reading. Thus, the undiluted test substance was selected as test concentration for the main study for both induction and challenge.

MAIN STUDY
Number of animals per control group: 10.
Number of animals of the test group: 20.
According to the authors, a second control group (control group 2) has been intended for a potential rechallenge in case of borderline results at the challenge.

A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: days 0, 7 and 14
- Test groups: 0.5 ml of the undiluted test substance
- Control group: the control groups were not treated, since the test substance was applied unchanged and thus no vehicle was used.
- Site: anterior left flank
- Frequency of applications: one application per week
- Duration: 6 hours
- Concentrations: undiluted
- Reading: 24 h after the removal of the patch

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 28
- Exposure period: 6 hours
- Test groups: 0.5 ml of the undiluted test substance
- Control group: 0.5 ml of the undiluted test substance (control group 1), untreated (control group 2)
- Site: right flank
- Concentrations: undiluted
- Evaluation (hr after challenge): 24 and 48 h after the removal of the patch

Since no borderline results were observed, a rechallenge was not performed.

OTHER:
determination of body weight

Evaluation criteria
The evaluation of the results is based on the criteria of the Commission Directive 96/54/EC of July 30, 1996 for the 22nd Amendment of the Directive 67/548 EEC (Publication No. L 248, p. 228 - 229, 1996).
The number of animals with skin findings at 24 and/or 48 hours after the removal of the patch is taken into account for the determination of the sensitization rate.
The evaluation "sensitizing" results if at least 15 per cent of the test animals exhibit skin reactions.
Challenge controls:
A separate positive control study was routinely conducted with alpha-hexylcinnamaldehyde techn. 85% (1998-02-19 to 1998 03-27) in accordance with GLP guidelines and the Testing guidelines mentioned above:
- two control groups of 10 animals each
- a test group of 20 animals
- three induction applications with alpha-hexylcinnamaldehyde, 25% in Lutrol E 400
- challenge with alpha-hexylcinnamaldehyde, 10% in Lutrol E 400
- rechallenge with alpha-hexylcinnamaldehyde, 10% in Lutrol E 400
Positive control substance(s):
yes
Remarks:
alpha-hexylcinnamaldehyde techn. 85%
Positive control results:
The positive control study was valid; see below.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: undiluted. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: undiluted. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: undiluted. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: undiluted. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Main study:

Induction:

The first, second and third induction with the undiluted test substance did not cause any signs of skin irritation in all test group animals.

Challenge:

The number of animals with skin findings after the challenge is summarized in the following table:

Group

Challenge

(Test substance undiluted)

skin reactions

Control group 1

0/10

Test group

0/20

x/y: number of positive reactions/number of animals tested (reading at 24 h and/or 48 h after the removal of the patch)

Body weights:

The expected body weight gain was generally observed in the course of the study.

Conclusion:

Based on the results of this study and applying the evaluation criteria it was concluded that DL-Panthenol does not have a sensitizing effect on the skin of the guinea pig in the BUEHLER Test under the test conditions chosen.

Positive control study (BASF report No. 32H0158/982065)

The positive control with Alpha-Hexylcinnamaldehyde techn. 85% showed that the chosen guinea pig strain was able to detect sensitizing compounds under the laboratory conditions chosen.

The number of animals with skin findings after the challenge and after the rechallenge is summarized in the following table:

Challenge

Rechallenge

a-Hexylcinnamaldehyde

10% in Lutrol E 400 DAB

Vehicle control

Lutrol E 400 DAB

a-Hexylcinnamaldehyde

10% in Lutrol E 400 DAB

Vehicle control

Lutrol E 400 DAB

24 h

48 h

Total

24 h

48 h

total

24 h

48 h

Total

24 h

48 h

total

Control group 1

0/10

0/10

0/10

0/10

0/10

0/10

0/10

0/10

0/10

0/10

0/10

0/10

Control group 2

No application of  test substance

0/10

0/10

0/10

0/10

0/10

0/10

0/10

0/10

0/10

Test group

4/19

2/19

4/19

0/19

0/19

0/19

5/19

3/19

5/19

0/19

0/19

0/19

x/y: number of positive reactions/number of animals tested (reading at 24 h and/or 48 h after the removal of the patch)

(*) 1 animal of the test group died 25 days after the beginning of the study. Macroscopic examination revealed that the cause of death was not substance-related.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the evaluation criteria , DL-Panthenol does not have a sensitizing effect on the skin.
Executive summary:

A skin sensitisation test in Hartley guinea pigs was performed according to OECD 406 and EU method B.6 (Maximisation test). Test substance concentrations selected for the main study were based on the results of a preliminary study. In the main study 20 animals of the test group and 10 animals of the control group were intradermally exposed to 0.5 mL of the undiluted test substance in three exposures of 6 hours each on day 0, 7, and 14. On day 28, the animals were challenged by the application of 0.5 mL of the undiluted test substance. Reading was performed 24 and 48 hours after patch removal. Based on the results of this study and applying the evaluation criteria it was concluded that DL-Panthenol does not have a sensitizing effect on the skin of the guinea pig in the BUEHLER Test under the test conditions chosen.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A read across on data available for DL-Panthenol was performed as both substances share similar physical-chemical properties. For justification of read across please refer to the attachment in IUCLID5 section 13. DL-Panthenol was tested for its sensitizing effect on the skin of the guinea pig in the BUEHLER Test. The first, second and third induction with the undiluted test substance did not cause any signs of skin irritation in all test group animals. A challenge was performed 14 days after the last induction. Based on the results of the read across and applying the evaluation criteria it was concluded that D-Panthenol does not have a sensitizing effect on the skin of the guinea pig in the BUEHLER Test under the test conditions chosen.

The results of the key study were confirmed in a supporting study with Bepanthen-Ointment containing 5 % test item performed in guinea pigs and rabbits. Thus, the substance was considered to be not skin sensitising.


Migrated from Short description of key information:
Based on the results obtained from testing, the substance was considered to be not skin sensitising.

Justification for selection of skin sensitisation endpoint:
The close structural similarity between DL- Panthenol and D- Panthenol strongly suggest that D-Panthenol is also not sensitising. For justification of read across please refer to the attachment in IUCLID5 section 13.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the results obtained from testing the substance was not classified and labeled acoording to Regulation (EC) No 1272/2008 (CLP) and Directive 67/548/EEC (DSD).