Registration Dossier

Administrative data

Description of key information

Not sensitising in guinea pig maximisation test.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
in vivo (guinea pig maximisation test)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
Test based on method described by Magnusson B. and Kligman A.M. in 'Allergic contact dermatitis in the guinea pig: identification of contact allergens', C.C. Thomas, Springfield, Illinois, 1970.
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study was already available
Species:
guinea pig
Strain:
other: Pribright white
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Stock, Gelnhausen
- Housing: 10 animals per cage
- Diet: ad libitum
- Water: ad libitum
Route:
intradermal
Vehicle:
other: Freund's complete adjuvant 50 : 50 in distilled water.
Concentration / amount:
1 %
Day(s)/duration:
day 0
Route:
intradermal
Vehicle:
water
Concentration / amount:
1 %
Day(s)/duration:
day 0
Adequacy of induction:
other: highest non irritant concentration
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
75 %
Day(s)/duration:
day 7 / exposure period 48 h
Adequacy of induction:
other: highest non irritant concentration
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
10 %
Day(s)/duration:
day 21 / exposure period 24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 animals.
Details on study design:
RANGE FINDING TESTS: highest non irritating concentration tested and adopted for main test were: 1 % in distilled water for intradermal injection; 75 % in paraffin for dermal application; 10 % in distilled water for dermal challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal injection
- no. of exposure: 1.
- area: 4 × 6 cm on shaved shoulder.
- 3 types of injections, each in left and right side of the area: 1) Freund's complete adjuvant 50 : 50 with distilled water; 2) 1 % test substance in distilled water; 3) Freund's complete adjuvat 50 : 50 with 1 % test substance in distilled water.

Dermal application
- no. of exposure: 1.
- day of exposure: 7 days after intradermal injection.
- area: 3 × 6 cm.
- exposure period: 48 hours.
- concentration: 75 % in paraffin.
- coverage: closed.

B. CHALLENGE EXPOSURE
Dermal application
- day of challenge: 14 days after dermal application.
- exposure period: 24 hours.
- concentration : 10 % in distilled water.
- coverage: closed.
- site: left flank.
- evaluation: 24, 48 and 72 hours after challenge.
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10 % in distilled water
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
slight oedema in two animals, but no erythema
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10 % in distilled water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
10 % in distilled water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation

animal E = erythema O = oedema observation time h
24 48 72
1 E  0 0 0
O 0 0 0
2 E  0 0 0
O 0 0 0
3 E  0 0 0
O 0 0 0
4 E  0 0 0
O 0 0 0
5 E  0 0 0
O 0 0 0
6 E  0 0 0
O 1 0 0
7 E  0 0 0
O 0 0 0
8 E  0 0 0
O 0 0 0
9 E  0 0 0
O 1 0 0
10 E  0 0 0
O 0 0 0
Interpretation of results:
GHS criteria not met
Conclusions:
The substance resulted as non sensitising in guinea pig maximisation test.
Executive summary:

Method

Guinea pig maximisation test according to method described by Magnusson and Kligman, 1970. Preliminary test allowed to choose concentrations for the main test. In particular, at day 0, induction was done by intradermal injection of test substance at 1 % concentration in distilled water and 50 : 50 distilled water and Freund's adjuvant; at day 7, induction was done by a 48 -h occlusive dermal application of test substance at 75 % concentration in paraffin ; at day 21, challenge was performed by a 24 -hour occlusive dermal application of test substance at 10 % in distilled water.

Results

Examination of treated areas was performed 24, 48 and 72 hours upon challenge exposure. 2/10 positive responses in terms of oedema were found at the 24-hour observation, then no positive responses were seen.

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

No data on the substance in itself (phosphate salification) was available, thus the assessment on skin sensitisation relied on data on a read-across substance, i.e. the chloride salification of the ssubstance. Details on the read-across approach are reported in section 13.

The sensitising potential was tested on guinea pigs in maximisation test by intradermal and epidermal exposure. Except for 2 positive responses 24 hours after challenge, no positive responses were seen up to 72 hours after challenge. Therefore the threshold for classification according to the CLP Regulation (EC 1272/2008) was not overcome.

Under test conditions, during the observation period, the substance appeared as non-sensitising and did not induce systemic toxicity.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The substance is not classified according to the CLP Regulation (EC 1272/2008). In the guinea pig maximisation test (adjuvant type), a positive response in less than 30 % (classification range 30 - 60 %) of the treated animals was found upon intradermal induction of the test substance at concentrations of 1 %. The assessment was done 24, 48 and 72 h after the challenge. Therefore, the substance may not be attributed to a sensitising category and the result is considered as negative.