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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:
1991
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Although nowadays in many member states of the EU the protocol byMagnusson and Kligmanis the preferred method, the Buehler test is a valid method according to OECD 406.
At the time of study conduction no such preference existed. The GPMT method was not preferred over the Buehler Test.
The Buehler test method has demonstrated its ability over the years to detect chemicals even with weak potential to sensitize human skin (Basketter DA, Gerberick GF. An interlaboratory evaluation of the Buehler test for the identification and classification of skin sensitizers. Contact Dermatitis. 35(3):146-51. 1996).
Thus, the Buehler test is a valid and reliable study to determine the skin sensitizing potency of PBO.
In the light of animal welfare a sensitization test according to the GPMT protocol was not conducted while a Buehler test was available

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
Source Davidson Mill Farm, Gamesbourg, NJ 08831, USA
Age/weight at study initiation 356 - 415 g
Number of animals per group 10 animals (Modified Buehler test)
Control animals 10 animals

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Remarks:
none
Concentration / amount:
0.4mL
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Remarks:
none
Concentration / amount:
0.4mL
No. of animals per dose:
10
Positive control substance(s):
yes
Remarks:
1-Chloro-2,4-dinitrobenzene (Eastman Kodak Co., Rochester, NY), as a 0.1% w/v dilution in 50% ethanol: 0.9 % saline solution

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.4 mL
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.4 ml
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Reading:
1st reading
Hours after challenge:
1
Group:
positive control
Dose level:
0.1% w/v dilution in 50% ethanol: 0.9% saline solution
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Erythema, Edema
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1% w/v dilution in 50% ethanol: 0.9% saline solution
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Erythema
Remarks on result:
positive indication of skin sensitisation
Group:
negative control
Remarks on result:
not measured/tested

Any other information on results incl. tables

Results of pilot studies:  

Prior to the main test, the test article was screened as supplied at concentrations of 75% v/v, 50% v/v and 25% v/v in corn oil (Mazola corn oil, Best Foods, CPC International Inc., Englewood cliffs, NJ 07632) to determine its minimal irritation threshold and its highest non-irritating concentration. After a 6-hour skin contact period, the test article at all levels produced no skin irritation.

1.1              Results of test

 

1.1.1         24h after challenge

All animals showed neither edema nor erythema 24 hours after termination of challenge

1.1.2         48h after challenge

All animals showed neither edema nor erythema 48 hours after termination of challenge

1.1.3         Other findings

The group of naive guinea pigs served as irritation controls also showed no effects.

-sensitization reaction: the test substance did not show any reactions at  any interval. 
Therefore, it is not a dermal sensitizer.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The naive positive control animals were negative at challenge. For the DNCB positive control sensitisation was demonstrated.
Although in the group treated with Piperonyl Butoxide there were scattered 1+ readings during the induction applications in the 10 test guinea pigs, the challenge application was completely negative. The naïve controls were all negative.
Piperonyl Butoxide has no sensitizing potential under the conditions of the Modified Buehler Test. Skin sensitization was not provoked following the challenge phase.
The test article administered dermally as supplied doesn’t appear to be a dermal sensitizer to albino guinea pigs, under the study conditions utilized.