Pyridoxine hydrochloride

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

Maximization Test

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Nov 2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The number of animals was not increased to 20 test and 10 control animals as highly recommended in the guideline. However, as no reaction was seen it is not considered ethical to perform an additional test.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted on July 17, 1992 (reported Paris, April 29, 1993)

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

(July 30, 1996)

Principles of method if other than guideline:

The number of guinea pigs in the test group was 10 (5 control animals were used). Although no skin reaction was seen after challenge, animals were not re-challenged.

GLP compliance:

yes (incl. QA statement)

Remarks:

(March 1999)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

-

Species:

guinea pig

Strain:

other: Lbm: GOHI (Himalayan spotted)

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd., Biotechnology & Animal Breeding Division, Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 298-335 g (pretest); 338-391 g (main study)
- Housing: Individually in Makrolon type-4 cages
- Diet: ad libitum, standard pellets
- Water: ad libitum, tap water
- Acclimation period: none (pre-test), 7 days (main study)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5-23
- Humidity (%): 39-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 10th July 2000 To: 21st August 2000

Route:

intradermal and epicutaneous

Vehicle:

water

Remarks:

(bi-distilled)

Concentration / amount:

15% (Intradermal injection) and 50% (Epidermal application)

Route:

epicutaneous, occlusive

Vehicle:

water

Remarks:

(bi-distilled)

Concentration / amount:

15% (Intradermal injection) and 50% (Epidermal application)

No. of animals per dose:

10 (test group), 5 (control group)

Details on study design:

RANGE FINDING TESTS:
Intradermal injections: test substance was tested at 50%, 25% and 15% in one animal, dermal reactions were assessed 24 hours later. All concentrations resulted in moderate and confluent erythema. The test item concentration selected for the main study was 15% which was the highest technically applicable consentration for intracutaneous injection.
Epidermal applications: Patches of filter paper were saturated with the test item at 50% (technically the highest possible concentration to be applied), 25%, 15% and 10% and kept occlusively on shaved skin (two animals) for 24 hours. Test substance was removed and skin treated with depilatory cream. The reaction sites were assessed 24 and 48 hours after removal of the bandage for erythema and oedema. All concentrations gave no reaction and thus the concentration selected for induction and challenge in the main study was 50%.

MAIN STUDY
A. INDUCTION EXPOSURE
Animals were injected intradermally with FCA, test item at 15% or FCA + test item (15%) (test group), 0.1 ml/site. On test day 7 (23 hour prior to epidermal application) the hair of test animals at the application site was clipped and the test area was pretreated with 0.5ml of 10% Sodium-Lauryl-Sulfate (SLS) in paraffinum perliquidum. The SLS was massaged into the skin with a glass rod without bandaging, provoking a mild inflammatory reaction. On day 8, guinea pigs were exposed occlusively via epidermal application (appr. 0.3 ml) for 48 hours. The reaction sites were assessed 24 and 48 hours after removal of the bandage for erythema and oedema.

B. CHALLENGE EXPOSURE
The test and control guinea pigs were challenged two weeks after the epidermal induction application and were treated in the same way (no SLS treatment).
The reaction sites were depilated 21 hours after removal of the bandage and assessed at 24 and 48 hours for erythema and oedema.

Challenge controls:

Negative control group was included (distilled water without test substance).

Positive control substance(s):

yes

Remarks:

Alpha-hexylcinnemaldehyde

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

challenge concentration = 50%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No signs of toxicity were observed in the animals.

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No signs of toxicity were observed in the animals..

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

challenge concentration = 50%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

challenge concentration = 50%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

No signs of toxicity were observed.

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No signs of toxicity were observed..

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

challenge concentration = 50%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

1 %

No. with + reactions:

7

Total no. in group:

10

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

1 %

No. with + reactions:

5

Total no. in group:

10

No mortality occurred during the study and no signs of clinical toxicity were observed in the animals during the study. The weight gain of the exposed animals did not differ from the weight gain of the control animals.

The expected and common findings were observed in the control and test group after the different applications using FCA intradermally. These findings consisted of erythema, oedema, necrotizing dermatitis, encrustation and exfoliation of encrustation.

Discrete/patchy erythema was observed in 3/5 control animals and 10/10 treated animals at the 24- and 48-hour reading after epidermal exposure during induction phase.

Interpretation of results:

not sensitising

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In a guinea pig maximisation test no skin sensitising effects of the test substance at a concentration up to 50% in distilled water was observed. Therefore, the test substance is no skin sensitiser.

Executive summary:

A guinea pig maximisation test was performed with 10 test and 5 control animals following OECD guideline and GLP principles. On test day 7 (23 hour prior to epidermal application in the induction phase) the test area was pretreated with 0.5 ml of 10% Sodium-Lauryl-Sulfate (SLS) in paraffinum perliquidum to provoke a mild inflammatory reaction. No mortality occurred, no clinical toxicity was seen and no unexpected changes in body weight gain were noted. After intradermal induction irritating effects were noted, and epidermal induction resulted in discrete/ patchy erythema with 50% test substance in water. After challenge, no skin effects of the test substance at a concentration up to 50% in distilled water was observed. Therefore, it is concluded that Pyridoxine Hydrochloride is no skin sensitiser.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

A guinea pig maximisation test was performed with 10 test and 5 control animals following OECD guideline and GLP principles. On test day 7 (23 hour prior to epidermal application in the induction phase) the test area was pretreated with 0.5 ml of 10% Sodium-Lauryl-Sulfate (SLS) in paraffinum perliquidum to provoke a mild inflammatory reaction. No mortality occurred, no clinical toxicity was seen and no unexpected changes in body weight gain were noted. After intradermal induction irritating effects were noted, and epidermal induction resulted in discrete/ patchy erythema with 50% test substance in water. After challenge, no skin effects of the test substance at a concentration up to 50% in distilled water was observed. Therefore, it is concluded thatPyridoxine Hydrochloride is no skin sensitiser.

Migrated from Short description of key information:
In a guinea pig maximisation test no skin sensitising effects of the test substance at a concentration up to 50% in distilled water was observed. Therefore, the test substance is no skin sensitiser.

Justification for selection of skin sensitisation endpoint:
One reliable study available (Klimisch 2).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Since there was no indication that the test substance elicited a sensitising reaction when tested up to 50%, Pyridoxine Hydrochloride is considered not to be a skin sensitizer and is not classified according to Regulation (EC) 1272/2008.