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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:
August-September 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted study according to GLP
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
conducted prior to adoption of LLNA method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Batch no. : 003513567
Storage: at room T in the dark

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
Concentration of test material and vehicle used at induction:
- Intradermal induction: 10% w/v in arachis oil BP - Topical induction: undiluted as supplied Concentration of test material and vehicle used for each challenge: Undiluted as supplied and 75% v/v in arachis oil BP
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
Concentration of test material and vehicle used at induction:
- Intradermal induction: 10% w/v in arachis oil BP - Topical induction: undiluted as supplied Concentration of test material and vehicle used for each challenge: Undiluted as supplied and 75% v/v in arachis oil BP
No. of animals per dose:
First study (106/031):
Number of animals in test group: 10
Number of animals in negative control group: 5
Second study (106/050):
Number of animals in test group: 10
Number of animals in negative control group: 5
Challenge controls:
yes
Positive control substance(s):
yes
Remarks:
mercaptobenzothiazole (CAS No 149-30-4)

Results and discussion

Positive control results:
OK

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
75 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100 %
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 7.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
75 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100 %
No. with + reactions:
5
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 5.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
75 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 75 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
75 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 75 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
other:
Hours after challenge:
48
Group:
positive control
Dose level:
50% in acetone:PEG 400 (70:30) (challenge); 5% 2-Mercaptobenzothiazole in arachis iol BP (induction); 50% in acetone:PEG 400 (70:30) (Topical);
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
100%
Reading:
other:
Hours after challenge:
48
Group:
positive control
Dose level:
25% in acetone:PEG 400 (70:30) (Challenge); 5% 2-Mercaptobenzothiazole in arachis iol BP (induction); 50% in acetone:PEG 400 (70:30) (Topical)
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

In the first study (106/031), at the challenge with undiluted (100%) test substance in both the test and the control animals effects of skin irritation were observed. Since these effects were observed in both test (8/10) and control (3/5) animals and
no effects whatsoever were observed in both test and control animals at the challenge concentration of 75% it was
concluded that owing to the irritancy of the 100% test material no sensitisation responses could be determined in
the 100% group. In the 75% challenge concentration no signs of irritation were observed. The test material was therefore
concluded not to cause sensitisation.

In the second report (106/050) it was, however, concluded that in the first study (106/031) 2/10 test animals showed a more severe reponse than the other animals and controls did. One of these two was killed for humane reasons 24 h after challenge (so that no data were available at 48 h).

As 5/10 (50%) of the animals showed slight skin reactions in the second study (106/050) at a challenge of 100% both at 24 h and 48 h after challenge, whereas controls did not, it was concluded that the overall sensitisation rate from these two studies was 7/20 (35%). Positive control group showed a 100% response to 2 -Mercaptobenzothiazole.

Signs of irritation during induction:
- Intradermal induction: Well defined to moderate to  severe erythema observed in all test group animals.
- Topical induction: Very slight to well-defined erythema with very slight oedema was noted in all test group animals at the 1 hour observation. In twelve test group animals very slight  to well-defined erythema was noted at the induction
sites after 24 hours.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Category 1B Criteria used for interpretation of results: EU
Conclusions:
It was concluded from 2 independent studies that the overall sensitisation rate was 35%, therefore requiring classification. However, based on the fact that challenge reactions were only observed when using the undiluted test substance (which is irritating), that these reactions were moderate and also seen in controls, and not observed at a concentration of 75%, it can also be concluded that the test substance is a weak sensitiser, if at all.
Executive summary:

It was concluded from independent studies that the overall sensitisation rate was 35%, therefore requiring classification. However, based on the fact that challenge reactions were only observed when using the undiluted test substance (which is irritating), that these reactions were moderate and also seen in controls, and not observed at a concentration of 75%, it can also be concluded that the test substance is a weak sensitiser, if at all.