D-Glucopyranose, oligomeric, heptyl glycosides

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:

05 Jun 2012 - 30 Aug 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Federal Republic of Brazil, Ministry of Development, Industry and Foreign Trade, National Institute of Metrology, Standardization and Industrial Quality

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The experimental study was performed in Brazil. At that moment there were no viable alternative, in vitro or otherwise, to the use of live animals was accepted by the relevant supervisory government agencies.

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: ANILAB-SP, Brazil
- Age at study initiation: 10 weeks
- Weight at study initiation: 404-556 g
- Housing: animals were housed in groups of 5 in 99 x 79 x 28 cm polypropylene cages with autoclaved wood shavings as bedding.
- Diet: pelleted commercial diet ‘Nuvilab Cobaias 6001’, ad libitum
- Water: filtered drinking water enriched with ascorbic acid (300 mg/L), ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22.9
- Humidity (%): 50-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 05 Jun 2012 To: 29 Jun 2012

Route:

intradermal and epicutaneous

Vehicle:

other: deionised water

Concentration / amount:

Induction, intradermal: 3.9% v/v
Induction, epicutaneous: 78.7% v/v (undiluted)
Challenge: 19.7% v/v

Route:

epicutaneous, occlusive

Vehicle:

other: deionised water

Concentration / amount:

Induction, intradermal: 3.9% v/v
Induction, epicutaneous: 78.7% v/v (undiluted)
Challenge: 19.7% v/v

No. of animals per dose:

10 (controls), 20 (in test group)

Details on study design:

RANGE FINDING TESTS:
A. Intradermal induction pilot study in two animals
- Test concentrations: 0.8, 1.6, 2.4, 3.1 and 3.9% a.i.
- Results: 3.9% of the test substance was chosen for the main study, since it was well tolerated systemically and the highest concentration causing slight to mild skin irritation in the animals 24 h after application.

B. Epicutaneous induction and challenge pilot study in two animals (tested on the same animals as in the intradermal induction pilot study)
Test concentrations: 19.7 and 78.7% a.i. (undiluted) (animal 1); 39.4 and 59% a.i. (animal 2)
-Results: 1 mL of the undiluted test substance was chosen for the topical induction because it was well tolerated systemically and the highest concentration causing slight to mild skin irritation in the animals 24 h after application. One mL of the test substance at 19.7% was chosen for challenge, since it was well tolerated systemically and the highest dose causing no skin reaction.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)

- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 (v/v) mixture FCA/deionised water
Injection 2: test substance at 3.9% a.i in deionised water
Injection 3: 3.9% a.i. formulation of the test substance on a 1:1 (v/v) mixture FCA/deionised water
Epicutaneous: undiluted test substance (78.7% a.i.)

- Control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 (v/v) mixture FCA/deionised water
Injection 2: deionised water
Injection 3: 50% v/v formulation of vehicle (deionised water) on a 1:1 (v/v) mixture FCA/deionised water
Epicutaneous: sham exposure (empty patches)

- Site: shoulder region (intradermal and epicutaneous)
- Frequency of applications: 7 days (Day 0 and Day 7)
- Duration: Days 0-9
- Concentrations: intradermal 3.9% a.i., epicutaneous 78.7% a.i. (undiluted)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: 21
- Exposure period: 24 h
- Test groups: test substance in deionised water
- Control group: test substance in deionised water
- Site: right flank
- Concentrations: 19.7% a.i.
- Evaluation (hr after challenge): 48 and 72 (i.e. 24 and 48 h after removal of patches)

Challenge controls:

The control group actually serves the purpose of a challenge control. No true challenge control included.

Positive control substance(s):

yes

Remarks:

alpha-hexylcinnamaldehyde

Positive control results:

The reliability check with the positive control substance alpha-hexylcinnamaldehyde (85%, technical grade) was performed in April 2012. In this study, alpha-hexylcinnamaldehyde (intradermal induction: 5% v/v; topical induction: 100% v/v; challenge: 25% v/v) induced discrete or patchy erythema (grade 1) and moderate and confluent erythema (grade 2) in 45% of the treated animals that persisted at both 48 and 72 h observation time points after challenge application. Therefore, treatment with the positive control alpha-hexylcinnamaldehyde met the reliability criteria for the GPMT (≥ 30% positive responses).

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

Induction: 0%; Challenge: 19.7% a.i.

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Induction: 0%; Challenge: 19.7% a.i.. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

Induction: 3.9% a.i.; Challenge: 19.7% a.i.

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: Induction: 3.9% a.i.; Challenge: 19.7% a.i.. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

1st reading

Hours after challenge:

48

Group:

positive control

Dose level:

Induction: 5% v/v; Challenge: 25% v/v

No. with + reactions:

9

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: positive control. Dose level: Induction: 5% v/v; Challenge: 25% v/v. No with. + reactions: 9.0. Total no. in groups: 20.0.

Reading:

2nd reading

Hours after challenge:

72

Group:

negative control

Dose level:

Induction: 0%; Challenge: 19.7% a.i.

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: Induction: 0%; Challenge: 19.7% a.i.. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

Induction: 3.9% a.i.; Challenge: 19.7% a.i.

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: Induction: 3.9% a.i.; Challenge: 19.7% a.i. . No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

2nd reading

Hours after challenge:

72

Group:

positive control

Dose level:

Induction: 5% v/v; Challenge: 25% v/v

No. with + reactions:

11

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: positive control. Dose level: Induction: 5% v/v; Challenge: 25% v/v. No with. + reactions: 11.0. Total no. in groups: 20.0.

Only treated animals presented skin reactions (moderate and confluent erythema) in the intradermal induction application. However, the observed skin reactions were due to skin irritation rather than sensitisation. Treated and control animals presented no skin reactions in the topical induction and challenge applications. No behavioral alterations were observed in the treated animals.

Conclusion:

The epidermal application of the test substance using deionised water as vehicle did not cause skin sensitisation in guinea pigs according to the Magnusson & Kligman Test Method.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In a GLP-compliant guinea pig maximisation test performed according to OECD 406, the skin sensitisation potential of D-Glucopyranose, oligomeric, heptyl glycoside was investigated (BIOAGRI, 2012). In the induction phase of the study, intradermal injections of the test substance at 3.9% a.i. in deionised water and/or FCA were applied to the clipped skin of 20 male Hartley guinea pigs. A control group, consisting of 10 males, was injected with the vehicle only and/or FCA. On Day 7, a 48-hour epicutaneous induction treatment with the undiluted test substance or sham-exposure with a blank cotton lint patch was performed in the treated and control animals, respectively, at the sites of intradermal injections. The challenge treatment on Day 21 was performed by topical application of the test substance at concentrations of 19.7% a.i. in deionised water to the right flank of all animals for 24 h. Skin reactions were evaluated 48 and 72 h after the initial challenge application. No skin reactions were provoked by the challenge treatment with the test substance in any of the control and treated animals. Alpha-hexylcinnamaldehyde in 25% v/v solution, which served as historical positive control, showed the expected results (> 30% positive response in the animals) and thus verified the reliability of the assay. Based on these results, the test substance had no sensitising effect on guinea pigs under the chosen experimental conditions.

Migrated from Short description of key information:
Skin sensitisation (OECD 406): not sensitising

Justification for selection of skin sensitisation endpoint:
There is only one study available.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Justification for selection of respiratory sensitisation endpoint:
Study not required according to Annex VII-X of Regulation (EC) No 1907/2006.

Justification for classification or non-classification

The available data on skin sensitisation of D-Glucopyranose, oligomeric, heptyl glycoside do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.