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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
A new protocol and criteria for quantitative determination of sensitization potencies of chemicals by guinea pig macimization test.
Author:
Nakaruma A, Momma J, Sekiguchi H. et al.
Year:
1994
Bibliographic source:
Contact Dermatitis, 1994; 31: 72-85.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Method: Magnusson and Kligman J. Invest. Dermatol 1969 ; 52 : 268-276
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A study on guinea pigs was available before the REACH regulation.

Test material

Constituent 1
Chemical structure
Reference substance name:
1,3-diphenyl-2-thiourea
EC Number:
203-004-2
EC Name:
1,3-diphenyl-2-thiourea
Cas Number:
102-08-9
Molecular formula:
C13H12N2S
IUPAC Name:
1,3-diphenylthiourea
Details on test material:
no data

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
- Strain: Hartley strain albino
- Sex: female (nulliparous and non-gravid)
- Source, age, weight at study initiation: no data
- preliminary study: no data

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: ethanol/propylene glycol (20/80)
Concentration / amount:
2, 20, 200, 2000 and 20000 ppm
Route:
epicutaneous, occlusive
Vehicle:
olive oil
Concentration / amount:
250000 ppm
Challenge
No.:
#1
Route:
epicutaneous, semiocclusive
Vehicle:
other: acetone
Concentration / amount:
0, 2, 20, 200, 2000 ppm
Day(s)/duration:
24h
No. of animals per dose:
10 females per dosed groups
. Negative controls (propylene glycol, petrolatum and acetone undiluted): yes, 1 group of 10 animals
Details on study design:
- Tested concentrations:
. For the induction: 2, 20, 200, 2000 and 20000 ppm were tested by intradermal injection. Each one of these concentrations was associated with a 250 000 ppm-concentration for the topical application. Moreover, a 0 ppm-concentration was tested too in induction stage (by both injection and topical routes).
. For challenge: each concentration used in induction stage was associated with 5 different concentrations in the challenge stage (topical application): 0, 2, 20, 200, 2000 ppm.

- Test procedure: performed almost in accordance with the original procedure of Magnusson and Kligman. So 21 days after the initial intradermal injection, 0.1 mL aliquots of various concentrations of test substance were applied on the flank of each animal for challenge.

- Challenge exposure duration: 24h

- Rechallenge: no
Challenge controls:
no
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
no induction
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Intradermal induction = 2 ppm
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Intradermal Induction = 20 ppm
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
other: Challenge 0 ppm (0/10), 2 ppm (1/10), 20 ppm (2/10), 200ppm (4/10), 2000 ppm (4/10)
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Intradermal induction= 200 ppm
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Challenge 0 ppm (0/10), 2 ppm (5/10), 20 ppm (8/10), 200ppm (10/10), 2000 ppm (10/10)
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Intradermal indution = 2000 ppm
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Challenge 0 ppm (0/10), 2 ppm (2/10), 20 ppm (8/10), 200ppm (10/10), 2000 ppm (9/10)
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Intradermal induction = 20 000 ppm
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Challenge 0 ppm (0/10), 2 ppm (9/10), 20 ppm (10/10), 200ppm (9/10), 2000 ppm (9/10)
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

- From the 2 ppm-challenge concentration, the MR as well as the SR,increased with
the challenge concentration, when the induction concentration was held constant.

- The minimum induction concentration of test substance that induces a
positive response = 20 ppm (because no positive reactions with any
challenge concentrations were found when the induction concentration was 2 ppm).

- The challenge concentration that induces a mean response approximately equal
to 1.0 among the animals applied with the highest concentration for induction
= 2 ppm.

Applicant's summary and conclusion

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
Positive responses were observed in this Guinea pigs maximalisation test, DPTU is considered as a strong skin sensitizer .
Executive summary:

A guinea pigs maximalisation test was performed according to the Magnuson and Kligman method with DPTU.


In induction phase, guinea pigs were exposed by intradermal injection (0, 2, 20, 200, 2000, 20000 ppm of DPTU) and by topical administration (0 or 250 000 ppm of DPTU). In the challenge phase, animals were exposed by topical administration at: 0, 2, 20, 200, 2000 ppm of DPTU.


No effect was observed in the animals which were not induced and/or challenge with DPTU (negative control).


Below 20 ppm ( induction phase), no cutaneous reactions were observed after the challenge application. In the animals induced by an injection of 20 ppm of DPTU, skin sensitisation was observed in all groups of challenged rats : 1/10 (2 ppm), 2/10 (20 ppm), 4/10 (200 and 2000 ppm). In the animals induced by an injection of 200 ppm of DPTU, skin sensitisation was observed in all groups of challenged rats : 5/10 (2 ppm), 8/10 (20 ppm), 10/10 (200 and 2000 ppm). In the animals induced by an injection of 2000 ppm of DPTU, skin sensitisation was observed in all groups of challenged rats : 2/10 (2 ppm), 8/10 (20 ppm), 10/10 (200 ppm) and 9/10 (2000 ppm). In the animals induced by an injection of 20000 ppm of DPTU, skin sensitisation was observed in all groups of challenged rats : 9/10 (2 ppm), 10/10 (20 ppm), 9/10 (200 ppm) and 9/10 (2000 ppm). 


 According this guinea pig maximalisation test, DPTU is a strong skin sensitizer .