Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
In-life: 24 days (September 11, 1989 to October 5, 1989)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to generally accepted international guidelines for the testing of skin sensitization.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
GLP compliance:
not specified
Remarks:
A quality assurance unit was noted in the study report.
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
-Identity (according to study report): tert.-Butanol
-Purity: 99.88%
-Impurities: 0.12% sec-Butanol
-Solid (Crystal), Colorless
-Specific gravity: 0.775
-Vapor Pressure: 40.7 hPa
-Melting Temperature: 25.5 °C
-Boiling Temperature: 82.5 °C
-Date test material produced: March 22, 1989
-Date test material received: March 23, 1989
-Prior to use, the crystallized test material was liquified in a 30-40 °C water bath.

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Albino; Bor: DHPW
Sex:
female
Details on test animals and environmental conditions:
-Breeder: F. Winkelmann, 4799 Borchen
-Acclimated: 5 - 8 days
-Mean weight of test group: 387 grams
-Mean weight of control group: 407 grams
-Identification: animals were distinctly marked with picric acid
-Caging: Makrolonkafigen Type IV.
-Diet: G4 Guinea pig diet (ad libitum)
-Water: tap water (ad libitum)
-Room temperature: 20 °C +/- 1 °C
-Relative humidity: 60% +/- 5%
-Air changes: 15 times/hour
-Lighting Cycle: 12 hours light/12 hours dark
-Randomization: Animals placed in cages using arbitrary numbers table

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
TEST ANIMALS
INDUCTION (Day 0)
Intradermal injections (2 pairs each):
-0.1 mL of Freunds Complete Adjuvant (FCA) and water (1:1)
-0.1 mL of 1% test material in water
-0.1 mL of 1% test material in FCA and water (1:1)
INDUCTION (Day 7)
Topical Application
-100% test material
CHALLENGE (Day 21)
Topical Application
-100% test material

CONTROL ANIMALS
INDUCTION (Day 0)
Intradermal injections (2 pairs each):
-0.1 mL of FCA and water (1:1)
-0.1 mL of water
-0.1 mL of a 50% formulation of water and FCA/water (1:1)
INDUCTION (Day 7)
Topical Application
-100% water
CHALLENGE (Day 21)
Topical Application
-100% test material
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
TEST ANIMALS
INDUCTION (Day 0)
Intradermal injections (2 pairs each):
-0.1 mL of Freunds Complete Adjuvant (FCA) and water (1:1)
-0.1 mL of 1% test material in water
-0.1 mL of 1% test material in FCA and water (1:1)
INDUCTION (Day 7)
Topical Application
-100% test material
CHALLENGE (Day 21)
Topical Application
-100% test material

CONTROL ANIMALS
INDUCTION (Day 0)
Intradermal injections (2 pairs each):
-0.1 mL of FCA and water (1:1)
-0.1 mL of water
-0.1 mL of a 50% formulation of water and FCA/water (1:1)
INDUCTION (Day 7)
Topical Application
-100% water
CHALLENGE (Day 21)
Topical Application
-100% test material
No. of animals per dose:
Test Group: 20 females
Control Group: 10 females
Details on study design:
INTRADERMAL INDUCTION (Day 0)
A 4x6 cm area of the back shoulders of each guinea pig was carefully clipped. Each guinea pig (test and control groups) received three pairs of intradermal injections (one of each pair situated on each side of the midline) of 0.1 mL of the appropriate concentrations (see box labelled "Concentration").

TOPICAL INDUCTION (Day 7)
Since no effect was noted with a 100% concentration of the test material in a prior preliminary dermal irritation test, an application of 10% sodium lauryl sulfate in vaseline was applied over the newly clipped area injection sites of each animal 24 hours prior to the topical induction phase to induce a local irritation reaction. One week after the intradermal injections, filter paper ( 2x4 cm) was loaded with 100% of the test material and applied to the application site of each test animal and held in contact by an occlusive dressing (5x3 cm patch) for a period of 48 hours. For control animals, only water was applied to the application sites, in a similar manner as the test animals.

CHALLENGE (Day 21)
The left flanks of treated and control animals were cleared of hair. Two to three hours later, each animal received filter paper (2x2 cm) fully loaded with 100% of the test material under an occlusive dressing for a period of 24 hours. Skin reactions were scored 24 and 48 hours after patch removal. The skin of the application sites was clipped 2 to 3 hours prior to the challenge readings.

BODY WEIGHTS
Body weights were recorded weekly.
Challenge controls:
Ten guinea pigs assigned to a control group received exposure doses of vehicle or test material as described in details on study design.
Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: Observations after intradermal injections
Group:
other: test and control groups
Dose level:
intradermal injection sites with FCA
No. with + reactions:
30
Total no. in group:
30
Clinical observations:
Strong erythema, edema, and necrosis observed at intradermal injection sites using FCA for test and control animals. Since some sites in each animal used FCA, all 30 animals responded. All non-FCA injection sites resulted in no reaction.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Observations after intradermal injections. Group: other: test and control groups. Dose level: intradermal injection sites with FCA. No with. + reactions: 30.0. Total no. in groups: 30.0. Clinical observations: Strong erythema, edema, and necrosis observed at intradermal injection sites using FCA for test and control animals. Since some sites in each animal used FCA, all 30 animals responded. All non-FCA injection sites resulted in no reaction..
Reading:
other: Observations after topical induction applications
Group:
other: test and control groups
Dose level:
100% test material for test animals and 100% water for control animals
No. with + reactions:
30
Total no. in group:
30
Clinical observations:
Animals agitated; 24-hr post patch removal, strong bloody inflammation/crust formation where FCA was used at injection sites; slight inflammation/erythema where test material was used.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Observations after topical induction applications. Group: other: test and control groups. Dose level: 100% test material for test animals and 100% water for control animals. No with. + reactions: 30.0. Total no. in groups: 30.0. Clinical observations: Animals agitated; 24-hr post patch removal, strong bloody inflammation/crust formation where FCA was used at injection sites; slight inflammation/erythema where test material was used. .
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100% test material
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No visible change
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100% test material. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No visible change.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100% test material
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No visible change
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100% test material. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No visible change.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100% test material
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No visible change
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100% test material. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No visible change.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100% test material
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No visible change
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100% test material. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No visible change.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Tertiary butyl alcohol is not classified as a skin sensitizer in female guinea pigs when tested in the Guinea Pig Maximization Test (GPMT) of Magnusson and Kligman.

Based on an absence of positive effects in this study, tertiary butyl alcohol is not classifiable for Skin Sensitization according to GHS.
Executive summary:

In a Guinea Pig Maximization Test for skin sensitization, a group of 20 female guinea pigs was exposed to undiluted tertiary butyl alcohol.  Under the conditions of this study, a concentration of 100% tertiary butyl alcohol at challenge did not cause a sensitization reaction after prior intradermal exposures of 1% and topical exposures of 100% tertiary butyl alcohol.