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Administrative data

Description of key information

Maximization test (Guinea pig-Pirbright White, GLP, OECD TG406): not sensitizing (Stark, 1998)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
the guinea pig maximisation test was an adequate in vivo skin sensitisation test at the time of performance in 1998 and the adjuvans-method thought to be more sensitive
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Dunkin Hartley Pirbright White guinea-pigs
- Source: Charles River Kislegg
- Age at study initiation: not reported
- Weight at study initiation: males 346-452 g, females 308-387 g
- Housing: 1-2 animals in conventional housing conditions (Makrolon type IV cages)
- Diet and water: ad libitum
- Acclimation period: > 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 64-66
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
intradermal induction: 5 % (w/v) test substance
epicutaneous induction: 25 % (w/v) test substance
challenge: 25 % (w/v) test substance
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
intradermal induction: 5 % (w/v) test substance
epicutaneous induction: 25 % (w/v) test substance
challenge: 25 % (w/v) test substance
No. of animals per dose:
10 (5/sex for test and control group)
Details on study design:
RANGE FINDING TESTS:
The 5 % (w/v) concentration of the test substance did not produce necrosis and ulcerations in the guinea pigs after intradermal application in
the same region in a previously conducted experiment. The 25 % (w/v) formulation was proved to provoke no necrosis to the skin in a previously performed local tolerance test.

MAIN STUDY
Intradermal induction:
5 male and 5 female guinea pigs (test group) received intracutaneously into the right and left dorsal neck region each 0.1 mL of diluted complete Freund's adjuvant, the test substance at a 5 % (w/v) concentration and the test substance at a 5 % (w/v) concentration mixed with complete Freund' s adjuyant. The control group (5/sex) received in the same way 0.1 mL of diluted Freund's complete adjuvant and the vehicle.

Epicutaneous induction:
On day 8 of the study, the same skin area of both groups was pretreated with sodium lauryl sulphate (10 w/v %) and thereafter on day 9 covered with a filter paper impregnated with the test substance at a 25 % (w/v) concentration in liquid paraffin for the test group, respectively impregnated with liquid paraffin only for the controls. The filter paper was kept under occlusive conditions by a bandage for 48 hours.

Challenge: On day 23, as a challenge, the same procedure was followed as on day 9 but the controls also received the filter paper impregnated with the test substance in liquid paraffin. The application was accomplished in the more sensitive flank region of the same animals. Furthermore, the occiusive bandage remained for only 24 hours. An evaluation of the reactions in the test as weIl as in the control group was carried out on day 25 and 26 of the study (48 and 72 hours after challenge).
Positive control substance(s):
not specified
Remarks:
historical control data with mercaptobenzothiazole available
Group:
positive control
Remarks on result:
not measured/tested
Remarks:
The sensitivity of the used method was proven by performance of a maximization test with mercaptobenzothiazole, a positive reference substance recommended in OECD guideline 406. This reference substance (mercaptobenzothiazole) was tested in Sep./Oct. 1997 in our laboratory. In the test 12 out of 16 animals reacted positively to the challenge with mercaptobenzothiazole.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
25 %
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
slight to moderate reddening
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25 %
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
slight reddening
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
10

slight reactions observed in both control and test group are regarded as local intolerance reactions and not as signs of sensitization

Interpretation of results:
GHS criteria not met
Conclusions:
The results of the present study did not give any indication that ZK 5690 has a contact-sensitizing
potential in the guinea-pig in the maximization test. Therefore, ZK 5690 should not be regarded as contact-sensitizer.
Executive summary:

In a preceding local tolerance test, the intracutaneous administration of the recommended maximum concentration of 5.0% (w/v) ZK 5690 was found to be tolerated without severe intolerance reaction. The concentration of 25% (w/v) ZK 5690 was tolerated epidermally without local findings. Therefore, these concentrations were chosen for induction and challenge.



5 male and 5 female Dunkin Hartley Pirbright White guinea-pigs (test group) each received intracutaneously 0.1 ml of diluted Freund's complete adjuvant (FCA), ZK 5690 [5.0% (w/v)] and ZK 5690 [10.0% (w/v)] diluted 1 + 1 with FCA. In the same way, the control group (5M, 5F) received 0.1 ml of the vehicle [0.9% (w/v) NaCI in aqua bidest.] with and without FCA. 


24 hours after the end of exposure, 8 out of 10 animals of the control group and 4 out of 10 animals in the test group showed slight local skin reactions in form of slight to moderate reddening, which was no longer observed 48 hours after end of exposure. Due to the higher incidence in the control group, the skin reactions are regarded as local intolerance reactions indicative of FCA lowering the local tolerance threshold and not as signs of a sensitizing potential of the compound. Because of the low incidence, the low severity and short duration of the findings in the test group, it. has not to be expected that the local intolerance reactions may have masked possible contact-sensitizing effects of the compound.
Therefore, the present maximization test is regarded as valid for estimation of the skin sensitizing potential of ZK 5690 which is not a skin sensitizer.

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

In a preceding local tolerance test, the intracutaneous administration of the recommended maximum concentration of 5.0% (w/v) ZK 5690 was found to be tolerated without severe intolerance reaction. The concentration of 25% (w/v) ZK 5690 was tolerated epidermally without local findings. Therefore, these concentrations were chosen for induction and challenge.
5 male and 5 female Dunkin Hartley Pirbright White guinea-pigs (test group) each received intracutaneously 0.1 ml of diluted Freund's complete adjuvant (FCA), ZK 5690 [5.0% (w/v)] and ZK 5690 [10.0% (w/v)] diluted 1 + 1 with FCA. In the same way, the control group (5M, 5F) received 0.1 ml of the vehicle [0.9% (w/v) NaCI in aqua bidest.] with and without FCA.


24 hours after the end of exposure, 8 out of 10 animals of the control group and 4 out of 10 animals in the test group showed slight local skin reactions in form of slight to moderate reddening, which was no longer observed 48 hours after end of exposure. Due to the higher incidence in the control group, the skin reactions are regarded as local intolerance reactions indicative of FCA lowering the local tolerance threshold and not as signs of a sensitizing potential of the compound. Because of the low incidence, the low severity and short duration of the findings in the test group, it has not to be expected that the local intolerance reactions may have masked possible contact-sensitizing effects of the compound.
Therefore, the present maximization test is regarded as valid for estimation of the skin sensitizing potential of ZK 5690 which is not a skin sensitizer.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

No classification required for skin sensitisation according to Regulation (EC) 1272/2008.