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Description of key information

In a Magnusson & Kligman maximisation study performed according to OECD guideline 406 and in compliance with GLP, groups of 20 female guinea pigs were induced intradermally at10% w/v and then topically with undiluted material. When challenged at 75 % v/v, no positive response was observed in induced animals.

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:
From October 22 to December 6, 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study conducted in compliance with OECD guideline 406 with minor deviations: lack of data about test substance.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
no data on purity and certificate of analysis of test substance
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study is a guinea maximisation test conducted in 1987.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Interfauna (UK) Limited, Huntingdon, UK
- Age at study initiation: 7-10 weeks
- Weight at study initiation: 308-395 g
- Housing: Housed in groups of up to four in solid-floor polypropylene cages
- Diet (e.g. ad libitum): Guinea Pig FD1 Diet (Special Diets Services Limited, Witham, UK), ad libitum
- Water (e.g. ad libitum): Mains tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 40-65%
- Air changes (per hour): 15/hour
- Photoperiod (hours dark / hours light): 12 hours dark / 12 hours light
Route:
intradermal and epicutaneous
Vehicle:
other: arachis oil (induction) and absolute ethanol (challenge)
Concentration / amount:
Range finding test:
- Intradermal induction exposure: 1, 5, 10 or 25% w/v in arachis oil
- Topical induction or challenge exposure: 50, 75 or 100% w/v in absolute ethanol

Main test:
- Intradermal induction exposure: 10% w/v in arachis oil
- Topical induction exposure: Undiluted
- Topical challenge exposure: 75% v/v in absolute ethanol
Route:
epicutaneous, occlusive
Vehicle:
other: arachis oil (induction) and absolute ethanol (challenge)
Concentration / amount:
Range finding test:
- Intradermal induction exposure: 1, 5, 10 or 25% w/v in arachis oil
- Topical induction or challenge exposure: 50, 75 or 100% w/v in absolute ethanol

Main test:
- Intradermal induction exposure: 10% w/v in arachis oil
- Topical induction exposure: Undiluted
- Topical challenge exposure: 75% v/v in absolute ethanol
No. of animals per dose:
- Range finding test: 1 or 2 animals/dose
- Main test: 10 and 20 animals for control and test, respectively
Details on study design:
RANGE FINDING TESTS:
- Intradermal induction exposure: Guinea pigs (1/dose) received injections (0.1 mL) of test material at concentrations of 1, 5, 10 or 25% w/v in arachis oil and observed for systemic toxicity and dermal irritation reactions at 24, 48 and 72 hours and 7 days
- Topical induction or challenge exposure: One or two guinea pigs [intradermally injected with Freund's Complete Adjuvant (FCA) 7 days earlier] applied with up to two dose levels of test material (50, 75 or 100% v/v) in absolute ethanol and observed for dermal irritation reactions at 1, 24 and 48 hours


MAIN STUDY
A. INDUCTION EXPOSURE: INTRADERMAL
- No. of exposures: One
- Test groups: Intradermally injected with 0.1 mL of FCA, 10% w/v test material in arachis oil and 10% w/v test material emulsion in 1:1 preparation of FCA plus arachis oil on Day 0
- Control group: Intradermally injected with FCA, arachis oil or FCA plus arachis oil (1:1) on Day 0
- Site: Shoulder region (40 mm x 60 mm) on each side of mid-line
- Duration: Days 0-6

B. INDUCTION EXPOSURE: TOPICAL
- No. of exposures: One
- Exposure period: 48 hours
- Test groups: Filter paper patch loaded with undiluted test material (0.2-0.3 mL) topically applied on Day 7 via occlusive patch
- Control group: Only filter paper patch topically applied on Day 7 via occlusive patch
- Site: Shoulder region on each side of mid-line
- Frequency of applications: Single application
- Duration: Days 7-21

C. CHALLENGE EXPOSURE: TOPICAL
- No. of exposures: One
- Day of challenge: Day 21
- Exposure period: 24 hours
- Test groups: Filter paper patch loaded with 0.1-0.2 mL of 75% v/v test material in absolute ethanol topically applied on Day 21 via occlusive patch
- Control group: Filter paper patch loaded with vehicle only topically applied on Day 21 via occlusive patch
- Site: 0 (vehicle) or 75% v/v test material in absolute ethanol was applied to left or right shorn flank (50-70 mm X 50 mm), respectively
- Evaluation (hour after removal of challenge patch): 24 or 48 hours
Challenge controls:
A patch loaded with the vehicle only applied to the left flank via occlusive patch
Positive control substance(s):
yes
Remarks:
Historical data: Formaldehyde (40% aqueous solution)
Concentration:
Not applicable
No. of animals per dose:
Not applicable
Details on study design:
Not applicable
Statistics:
Not applicable
Positive control results:
Historical data (From March 4 to 28, 1987): Incidence of sensitisation for 40% formaldehyde was 95% (19/20) and classified as an extreme sensitiser to guinea pig skin.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
75% v/v in absolute ethanol
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: 75% v/v in absolute ethanol. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
75% v/v in absolute ethanol
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: 75% v/v in absolute ethanol. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.
Parameter:
SI
Remarks on result:
other: Not applicable
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Not applicable

Table 1: Intradermal sighting test - summary of results

 

Animal identification

Time of observation

Concentration of test material in arachis oil (% w/v)

Evidence of necrosis

Evidence of systemic toxicity

A

24 hours

1

None

None

48 hours

None

None

72 hours

None

None

7 days

None

None

B

24 hours

5

None

None

48 hours

None

None

72 hours

None

None

7 days

None

None

C

24 hours

10

None

None

48 hours

None

None

72 hours

None

None

7 days

None

None

D

24 hours

25

Necrosis

None

48 hours

Necrosis

None

72 hours

Eschar

None

7 days

Eschar

None

Conclusion: The concentration of the test material selected for the intradermal induction stage of the main study was 10% w/v in arachis oil BP

 

Table 2: Topical sighting test: Evaluation of reactions

 

Animal

identification

Concentration of test material in absolute alcohol (% v/v)

Evaluation of application sites (hours after removal of patches)

1

24

48

E

100

2

0

0

50

2

0

0

F

100

2

0

0

50

1

0

0

G

100

2

1

0

75

1

0

0

H

100

2

1

0

75

2

0

0

Conclusion: The undiluted test material and 75% (v/v) in absolute ethanol were selected for the main study topical induction and challenger, respectively.

 

Table 3: Main test: Topical induction - evaluation of reactions in test animals

No. of animals

Skin reaction (immediately after removal of dressings)

Test material: HR 87/600001

5

0

12

1

3

2

Control: Blank patch only

10

0

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
The test item is not classified according to Directive 67/548/EEC and CLP Regulation (EC) n° 1272/2008.
Executive summary:

In a Magnusson & Kligman maximisation study (GPMT) performed according to OECD guideline 406 and in compliance with GLP, groups of 20 female albino Dunkin-Hartley guinea pigs were intradermally induced with three injections of 0.1 mL of FCA, 10% w/v of test item in arachis oil and 10% w/v of test item emulsion in FCA on Day 0 on shoulder region on each side of mid-line. Control group of 10 animals was induced with FCA, arachis oil and 50% w/v arachis oil in FCA intradermal injections. After one week the same area was topically induced with 0.2-0.3 mL of undiluted test material via occluded filter paper patch for 48 hours for the treated group. Control group was patched with nothing applied to the filter paper. After 2 weeks of rest period, a challenge patch of 0 or 75% v/v test material in absolute ethanol was applied to left or right shorn flank of all animals, respectively. The test concentrations for the main study were determined from a sighting study using one or two animals.

 

Intradermal and topical induction indicated evidence of dermal irritation. No skin reactions were noted at the challenge sites of the test or control group animals at the 24 or 48-hour observations. The test item produced a 0% (0/20) sensitisation rate and was considered to be a nonsensitiser to guinea pig skin. Historical data on positive control (40% formaldehyde) exhibited evidence of sensitisation.

 

Therefore, the test item is not classified according to Directive 67/548/EEC and CLP Regulation (EC) n° 1272/2008.

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

In a Magnusson & Kligman maximisation study performed according to OECD guideline 406 and in compliance with GLP, groups of 20 female guinea pigs were induced intradermally at 10% w/v and then topically with undiluted material. When challenged at 75 % v/v, no positive response was observed in induced animals.

In a Magnusson & Kligman maximisation study performed similarly to OECD Guideline 406, 6 females and 4 males were induced intradermally at 2% v/v and then topically with undiluted material. When challenged at 25 % v/v, 2/9 animals had a positive response.


Migrated from Short description of key information:
The test substance was found negative in two Magnusson & Kligman maximisation studies.

Justification for selection of skin sensitisation endpoint:
GLP study conducted in compliance with OECD guideline 406 with only minor deviations

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

As the substance was found negative in two Magnusson & Kligman maximisation studies, it is not classified according to Directive 67/548/EEC and CLP Regulation (EC) n° 1272/2008.