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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:
April 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This Guinea pig maximisation test realised in 1999 before the publication of the Murine Local Lymph Node Assay (LLNA) Performance standards by ECVAM in 2008.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
yellow liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
Source: C. River - 76140 CLEON
Weight: about 200 to 250 g at the time of trial
Acclimatation: at least 5 days in the animal house of laboratory.
Housing: the animals are kept in individual polystyrene cages of standardized dimension with perforated floor. These cages are placed in temperature controlled animal shelter where the temperature is between 18 and 22°C and the relative humidity is maintained at between 50 and 80%
Food: aliment réf: 106, UAR - Villemoisson 91360 EPINAY SUR ORGE
Water: tap water ad libitum in sterilizable makrolon bottles equipped with stainless steel pipettes.

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, semiocclusive
Vehicle:
physiological saline
Concentration / amount:
Group 1:
- 2 intradermic injections of Freunds's complete adjuvant (50% dilution in the sterile isotonic solution of NaCl)
- 2 injections of 0.1 ml of NaCl 0.9%

Group 2:
- 2 intradermic injections of Freunds's complete adjuvant (50% dilution in the sterile isotonic solution of NaCl)
- 2 intradermic 0.1 ml injections of the test item diluted to 50% in NaCl 0.9%
- 2 intradermic 0.1 ml injections ofof a mixture of equal volumes of the two previous solutions
Day(s)/duration:
10 days.
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
Challenge
Route:
epicutaneous, semiocclusive
Vehicle:
physiological saline
Concentration / amount:
0.25 ml of the undiluted test item (which is the MNIC determined)
Day(s)/duration:
24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Induction phase and Trigger phase:
Group 1 treated: 5 females to check for the absence of a primary skin irritant effect at the time of the trigger phase
Group 2 control: 10 females used to assess whether the product has any sentizing power

Determination of the MNIC (Maximal non-Irritant Concentration)
3 animals
Details on study design:
Preliminary study: determination of the Maximum non-irritant concentration:
The dorso-lumbar zone of 3 animals was shaved and the hair was removed with cream. Then, the animals received two differents concentrations of the products under semi-occlusive dressing for 24 hours:
- undiluted
- in solution 1/2
- in solution 1/4
- in solution 1/8
- in solution 1/16
- in solution 1/32
in NaCl 0.9%

Induction phase (as described above)

Trigger phase (as described above cf. challenge)
Challenge controls:
Group 2: 10 females used to assess whether the product has any sentizing power
Positive control substance(s):
yes
Remarks:
1-chloro-2-4 dinitrobenzene : 1% in alcohol tested in the same conditions dispayed 100% of positive reactions

Results and discussion

Positive control results:
1-chloro-2-4 dinitrobenzene : 1% in alcohol tested in the same conditions dispayed 100% of positive reactions

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Hours after challenge:
72
Group:
test group
Dose level:
0.25 ml of the undiluted test item (which is the determined MNIC)
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
no sensitization effect observed
Remarks on result:
no indication of skin sensitisation
Key result
Hours after challenge:
72
Group:
negative control
Dose level:
0.25 ml of the undiluted test item (which is the determined MNIC)
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
no skin sensitization effect observed
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The lesions observed following the trigger application of DTP Riz at the Maximum Non Irritant Concentration did not display any sensitizing potential in the animals tested.
The positive reference (1-chloro-2-4 dinitrobenzene 1%) tested in the same conditions displayed 100% of positives reactions.
The Test Item displays a very slight sensitizing power in the albino guinea pig.
Executive summary:

The test item was tested according to the OECD 406 guidelines.

The determination of the MNIC was made by observations on 3 animals submitted to the following concentrations: undiluted product, 1/2; 1/4; 1/8; 1/16 and 1/32 in NaCl 0.9%.

The non diluted product does not provoke an orthoergic irritative skin irritation. The pure product is used for the trigger phase.

The lesions observed following the trigger application of DTP Riz at the Maximum Non Irritant Concentration did not display any sensitizing potential in the animals tested.

The positive reference (1-chloro-2-4 dinitrobenzene 1%) tested in the same conditions displayed 100% of positives reactions.

The Test Item displays a very slight sensitizing power in the albino guinea pig.