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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP non-guideline study, published in an industrial toxicology report on MTBE , minor restrictions, acceptable for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980

Materials and methods

Principles of method if other than guideline:
Dermal sensitization study in guinea pigs: Landsteiner technique
GLP compliance:
no
Type of study:
other: Dermal sensitization study in guinea pigs: Landsteiner technique
Justification for non-LLNA method:
Study conducted pre-dates provision of LLNA guideline.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
ARCO MTBE: 96.2%; commercial MTBE (Huls): 99.1% (not specified which sample was tested).
Batch number: LBI No. 5028
Storage: under refrigeration
Physical state: clear liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River
- Acclimation period: 2 weeks


Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: saline
Concentration / amount:
0.1%
Challengeopen allclose all
Route:
intradermal
Vehicle:
other: saline
Concentration / amount:
0.1%
No. of animals per dose:
10
Details on study design:
Ten guinea pigs were induced with an initial induction of 0.5 ml of a 0.1% MTBE solution in saline. Every second day for the next three weeks, the animals recieved an intradermal injection of 0.1 ml for a total of ten injections.
Fifteen days after the last injection, the guinea pigs received an intracutaneous challenge injection (0.05 ml of 0.1% solution of MTBE) below the sensitisation site.
Skin reactions were evaluated 24 and 48 hours after treatment and scored 0 to 4 for erythema, oedema and colour using the method of Draize.
The test material was judged to be a sensitizer, if the average of the challenge reactions was greater than the average of the sensitizing reactions by at least 25% in the majority of the animals tested.
Challenge controls:
0.05 ml of a 1-% solution of 2,4-dinitro-1-chlorobenzene was given to a positive control group of ten guinea pigs.
Positive control substance(s):
yes
Remarks:
2,4 dinitro-1-chlorobenzene (DNCB)

Results and discussion

Positive control results:
The results show that DNCB treatment produced a three-fold increase in the diameter of the reaction and a marked increase in erythema 24 hours following the challenge injection.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
induction: 0.05 ml of 1% solution of 2,4-dinitro-1-chlorobenzene; challenge: 0.05 ml of 1% solution of 2,4-dinitro-1-chlorobenzene
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Observations revealed very slight to well defined erythema throughout the study.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: induction: 0.05 ml of 1% solution of 2,4-dinitro-1-chlorobenzene; challenge: 0.05 ml of 1% solution of 2,4-dinitro-1-chlorobenzene. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Observations revealed very slight to well defined erythema throughout the study. .
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Induction: 0.05 ml of 1% solution of 2,4-dinitro-1-chlorobenzene; challenge: 0.05 ml of 1% solution of 2,4-dinitro-1-chlorobenzene
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Observations revealed very slight to well defined erythema throughout the study
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: Induction: 0.05 ml of 1% solution of 2,4-dinitro-1-chlorobenzene; challenge: 0.05 ml of 1% solution of 2,4-dinitro-1-chlorobenzene. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Observations revealed very slight to well defined erythema throughout the study.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction: 0.5 ml of 1% MTBE in saline, followed by 9 injections of 0.1 ml 1% MTBE in saline; challenge: 0.05 ml of 1% MTBE in saline
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Observations revealed very slight to well defined erythema with occasional edema throughout the study
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Induction: 0.5 ml of 1% MTBE in saline, followed by 9 injections of 0.1 ml 1% MTBE in saline; challenge: 0.05 ml of 1% MTBE in saline. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Observations revealed very slight to well defined erythema with occasional edema throughout the study.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 0.5 ml of 1% MTBE in saline, followed by 9 injections of 0.1 ml 1% MTBE in saline; challenge: 0.05 ml of 1% MTBE in saline
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
Observations revealed very welight to well defined erythema with occasional edema throughout the study
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Induction: 0.5 ml of 1% MTBE in saline, followed by 9 injections of 0.1 ml 1% MTBE in saline; challenge: 0.05 ml of 1% MTBE in saline. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: Observations revealed very welight to well defined erythema with occasional edema throughout the study.
Group:
negative control
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

MTBE treatment produced no significant increase in the response of the challenge injection as compared to the initial sensitizing or inducing injection.

The dose of MTBE used as the initial injection of 0.5 ml of a 0.1% solution did produce a local irritant effect which would indicate that an effective level was used.

Applicant's summary and conclusion