Panthenol , DL-form

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key 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:

other: GLP guideline study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted July 17, 1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

1996

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-6 (Skin Sensitisation)

Version / remarks:

revised November 1984

Deviations:

no

Principles of method if other than guideline:

The study was 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:

A guinea pig skin sensitization test (Buehler method), which was conducted in 1999 in compliance with OECD 406 guideline and under GLP, is already available for the test item. According to the Guidance on Information Requirements R.7a, section R.7.3.4.1 (pp 283-4) “existing data of good quality that were generated before 10 May 2017, or for which the study was initiated before 10 May 2017, and derived from such tests are acceptable; and if these tests provide clear results that are adequate for classification, even when a conclusion on potency (Cat. 1A or not) cannot be drawn, they will preclude the need for further in vivo testing.” In addition, information on the (non-)sensitization potential of the test item can be drawn by its long-standing use in personal care products.
Based on the long-term use of Panthenol in Personal Care products without evidence of sensitization, augmented with an available skin sensitization test in guinea pigs of good quality, the conduct of another animal test is not justified

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, FRG
- 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 %
- Air changes (per hr): no data
- 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 freetext below.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

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 chemical

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 D,L-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 the results of this study show 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.

Executive summary:

DL-Panthenol was tested for its sensitizing effect on the skin of the guinea pig in the BUEHLER Test according to OECD 406 and under GLP.

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.

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)

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:

In the key GLP and guideline study, DL-Panthenol was tested for skin sensitization in the Buehler test according to OECD guideline 406/EU method B.6. In the test group of 20 Pirbright White Dunkin Hartley guinea pigs, the test substance was applied undiluted in the induction and challenge application. A control group of 10 animals was used. 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.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.

A read across approach was performed with the supporting substance DL-Ethylpanthenol. For justification of read across please refer to the attachment in IUCLID5 section 13.

In a supporting GLP and guideline study, the skin sensitizating properties of DL-Ethylpanthenol were evaluated in a Maximization test with guinea pigs according to OECD guideline 406/EU method B.6. A test group of 10 albino guinea pigs and a control group of 5 animals were investigated for signs of skin hypersensitivity after intradermal and epidermal exposure. Under the conditions used in this study, exposure of DL-Ethylpanthenol induced no sensitisation.

Migrated from Short description of key information:
DL-Panthenol was tested for its sensitizing effect on the skin of the guinea pig in the BUEHLER Test. 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. A read across approach was performed in addition with the supporting substance DL-Ethylpanthenol. DL-Ethylpanthenol showed no sensitization in a maximization test with guinea pigs.

Justification for selection of skin sensitisation endpoint:
GLP and guideline study.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the results obtained from the key study and the supporting study , DL-Panthenol was not classified and labeled according to Regulation (EC) No 1272/2008 (CLP) and Directive 67/548/EEC (DSD).