tert-butyl methyl ether

Skin sensitisation

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

Test material information

Constituent 1

Reference substance name:

tert-butyl methyl ether

EC Number:

216-653-1

EC Name:

tert-butyl methyl ether

Cas Number:

1634-04-4

Molecular formula:

C5H12O

IUPAC Name:

2-methoxy-2-methylpropane

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)

Induction

Induction 1

Route:

intradermal

Vehicle:

other: saline

Induction 2

Concentration / amount:

0.1%

Challenge

Challenge 1

Route:

intradermal

Vehicle:

other: saline

Challenge 2

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)

Results

Results 1

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. .

Results 2

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.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

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.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

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.

Results 5

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.