Registration Dossier

Administrative data

Description of key information

The test substance was not considered to be skin sensitizing

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From November 12, 1998 to December 04, 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
RA study
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A GPMT study was submitted as this was already available before the requirement for LLNA testing was published.
Species:
guinea pig
Strain:
other: Pirbright-White
Sex:
female
Details on test animals and environmental conditions:
From: Harlan Winkelmann
Bodyweight (mean): 368 g
Temperature: 20 +/- 3°C and Relative humidity: 50 +/- 20%
Lighting time: 12 h daily
Food and water: ssniff Ms-H (V2233) and tap water (ad libitum)
Route:
intradermal
Vehicle:
water
Remarks:
deionized
Concentration / amount:
- 50% Freund's Complete Adjuvant emulsion
- 5% test substance (treatment group) or vehicle (control group)
- 50% Freund's Complete Adjuvant emulsion mixed with an equal volume of the test substance treatment group) or vehicle (control group)
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
deionized
Concentration / amount:
25% in 0.5 mL test substance (treatment group) or vehicle (control group)
Day(s)/duration:
48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
deionized
Concentration / amount:
5% in 0.5 mL test substance (treatment group) or vehicle (control group)
Day(s)/duration:
24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
- Range finding test:
Determination of the primary non-irritant concentration: 3
Determination of the tolerance of the intradermal injections :2
- Main study
Control group 5
Test substance group 10
Details on study design:
Range finding tests:
Determination of the primary non-irritant concentration
Determination of the tolerance of the intradermal injections
Main study:
A. Induction exposure: the administration area was examined for local tolerance. Any toxic effects were recorded.
B. Challenge exposure: examinations of the skin ca. 24 and 48 h after removal of patches (= 48 and 72 h after start of challenge)
NB. Body weights of the test animals were determined as well
Challenge controls:
left flank
Positive control substance(s):
no
Positive control results:
-
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation

Observations:

- Determination of the primary non-irritant concentration:

After administration of the 25% test substance concentration discrete or patchy erythema were observed in one animal. No signs of irritation occurred after administration of the 5% and 1% test substance concentration.

- Determination of the tolerance of the intradermal injections:

The intradermal injections with the 5.0% preparation caused slight up to well-defined erythema and oedema. The intradermal injections with the 1.0% preparation caused slight erythema.

The intradermal injections with the 0.2% preparation caused no signs of irritation.

- Intradermal induction:

The intradermal injections with Freund's Adjuvant (with or without test substance) caused severe erythema and edema as well as indurations and encrustations. When the test substance was administered with deionized water, slight erythema and oedema were observed. The vehicle alone did not cause any sign of irritation.

- Dermal induction:

After removal of the patches, severe erythema and edema, indurated, scabbed and encrusted skin as well as necrosis were observed at the sites peviously treated with Freund's Adjuvant. The daministration sites treated with the test substance showed slight erythema. The vehicle alone showed no signs of irritation.

- Dermal challenge:

No skin reactions were observed in the control and treatment groups, 24 and 48h after removal of the occlusive bandage.

- The body weight gains of the animals animals were not impaired. The treated animals showed no clinical signs of intoxication throughout the study.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the substance was not considered to be sensitizing to guinea pig skin.
Executive summary:

A study was conducted to determine the in vivo skin sensitisation potential of the read-across substance according to OECD Guideline 406 and EU Method B.6, in compliance with GLP. Female Pirbright-White guinea pigs (5 per control group and 10 per test group) were first exposed to the substance intradermally (injections of 50% Freund’s Adjuvant, 5% test substance in deionized water or 5% test substance in 50% Freund’s Adjuvant) and dermally (25.0% test substance in deionized) for 48 h. The dermal challenge consisted of application of an occlusive bandage for 24 h with 5.0% test substance in deionized water. Examinations were conducted 24 and 48 h after removal of the patches. None of the ten treated animals showed a positive skin response after the challenge procedure. Under the study conditions, the substance was not considered to be sensitizing to guinea pig skin (Seeberger, 1999).

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitisation, in vivo:

A study was conducted to determine the in vivo skin sensitisation potential of the read-across substance according to OECD Guideline 406 and EU Method B.6, in compliance with GLP. Female Pirbright-White guinea pigs (5 per control group and 10 per test group) were first exposed to the substance intradermally (injections of 50% Freund’s Adjuvant, 5% test substance in deionized water or 5% test substance in 50% Freund’s Adjuvant) and dermally (25.0% test substance in deionized) for 48 h. The dermal challenge consisted of application of an occlusive bandage for 24 h with 5.0% test substance in deionized water. Examinations were conducted 24 and 48 h after removal of the patches. None of the ten treated animals showed a positive skin response after the challenge procedure. Under the study conditions, the substance was not considered to be sensitizing to guinea pig skin (Seeberger, 1999).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the results of in an vivo skin sensitisation study with the read-across substance, the substance does not warrant classification for skin sensitisation according to EU CLP (EC 1272/2008) criteria.