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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1995-05-24 till 1995-09-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP and without deviations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Existing guideline study data under GLP were considered to be sufficient for REACH registration.

Test material

Constituent 1
Chemical structure
Reference substance name:
Methylphosphonic acid, compound with amidinourea (1:1)
EC Number:
282-758-4
EC Name:
Methylphosphonic acid, compound with amidinourea (1:1)
Cas Number:
84402-58-4
Molecular formula:
C2H6N4O.CH5O3P
IUPAC Name:
methylphosphonic acid, compound with amidinourea (1:1)
Details on test material:
technical product

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% v/v / 0.1 mL test chemical per site
Day(s)/duration:
Day 1 / single application
Adequacy of induction:
highest technically applicable concentration used
Route:
epicutaneous, semiocclusive
Concentration / amount:
100% v/v / 0.5 mL undiluted test substance
(treatment of all animals with 10% SDS approximately 24 hours before the epidermal induction, on Day 7)
Day(s)/duration:
Day 8 / 48 hours
Adequacy of induction:
highest technically applicable concentration used
Challengeopen allclose all
No.:
#1
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
1st Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
Day(s)/duration:
Day 22 / single application / 24 hours
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
2nd Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
Day(s)/duration:
Day 28 / 24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Preliminary study: 4 females
Experimental group: 10 females
Control group: 5 females
Details on study design:
Based on the results of the preliminary study, the test substance concentrations for the main study were
selected to be the undiluted test substance for the intradermal and epidermal induction exposures.
Since no or negligible signs of irritation were observed to the concentration
selected for the epidermal induction, it was decided to treat all animals with
10% SDS approximately 24 hours before the epidermal induction.
The undiluted and a 50% and 25% concentration were selected for the challenge
phase.
Positive control substance(s):
yes
Remarks:
alpha-Hexylcinnamicaldehyde techn. 85%

Results and discussion

Positive control results:
The results of using using alpha-Hexylcinnamicaldehyde (techn. 85%) as positive control confirmed the skin sensitisation potential of alpha-Hexylcinnamicaldehyde and thereby the sensitivity and reliability of skin sensitisation study in guinea pig.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
other: Second challenge - Day 32 readings
Hours after challenge:
48
Group:
test chemical
Dose level:
2nd Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: Second challenge - Day 31 readings
Hours after challenge:
24
Group:
test chemical
Dose level:
2nd Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Reading:
other: First challenge - Day 24 readings
Hours after challenge:
24
Group:
test chemical
Dose level:
1st Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
No. with + reactions:
3
Total no. in group:
9
Clinical observations:
skin reaction, grade 1
Remarks on result:
other: In the first challenge phase, 4 animals showed sporadic and inconsistent skin reactions. For confirmation, a 2nd challenge was performed one week later to the same concentrations.
Reading:
other: First challenge - Day 25 readings
Hours after challenge:
48
Group:
test chemical
Dose level:
1st Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
No. with + reactions:
2
Total no. in group:
9
Clinical observations:
none
Remarks on result:
other: In the first challenge phase, 4 animals showed sporadic and inconsistent skin reactions. For confirmation, a 2nd challenge was performed one week later to the same concentrations.
Key result
Reading:
other: First challenge - Day 24 readings
Hours after challenge:
24
Group:
negative control
Dose level:
1st Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: First challenge - Day 25 readings
Hours after challenge:
48
Group:
negative control
Dose level:
1st Challenge, Topical Application: 100% , 50%, and 25% test item and the vehicle (0.05 ml)
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
ALPHA-HEXYLCINNAMICALDEHYD (85%)
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
not reported
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
ALPHA-HEXYLCINNAMICALDEHYD (85%)
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
not reported
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

One experimental animal was found dead on day 16. No clinical signs were 


Since the four animals, which showed skin reactions in the first challenge


phase, showed no reactions in the second challenge to the same concentration, it


was considered that these responses were non-specific signs of irritation and


were not indicative of sensitisation. Therefore, it was concluded that no


evidence was obtained that the test item had caused contact hypersensitivity in the


guinea pig.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item was assessed for skin sensitization using the Magnusson & Kligman Maximisation test (OECD 406). None of the animals showed skin reactions with the test item by the second challenge. These data clearly demonstrate that the test item has no sensitization potential.
Therefore, the test item is not to be classified as "sensitizer".