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Toxicological information

Skin sensitisation

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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test
Justification for non-LLNA method:
Test according EPA OPP-81-6

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): dipropylene glycol
- Molecular formula (if other than submission substance): C6H14O3
- Molecular weight (if other than submission substance): 134.1736
- Smiles notation (if other than submission substance): CCC(O)OC(O)CC
- InChl (if other than submission substance): InChI=1/C6H14O3/c1-3-5(7)9-6(8)4-2/h5-8H,3-4H2,1-2H3
- Physical state: clear viscous liquid
- Analytical purity: 100%
- Lot/batch No.: TB41213-04-2
- Storage condition of test material: in the original container (blue metal can) at room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Camm Research Lab Animals, Wayne, New Jersey
- Age at study initiation: young adult
- Weight at study initiation: males: 386 to 455 g; females: 355 to 422 g
- Housing: housed individually under standard laboratory conditions in the study room.
- Diet (e.g. ad libitum): Camm Guinea Pig Diet or equivalent
- Water (e.g. ad libitum): potable municipal water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature: 68-74ºF
- Humidity (%): 35-65%
- Photoperiod (hrs dark / hrs light): 12 hours on/12 hours off cycle

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Undiluted 0.5 ml
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Undiluted 0.5 ml
No. of animals per dose:
Test animals: 10 animals; 7 male, 3 female
Control Animals: 5 animals; 3 male, 2 female
Details on study design:
RANGE FINDING TESTS:
To determine the correct concentrations to be used for induction (minimal irritation) and challenge (non-irritating), 5 guinea pigs were exposed to 4 concentrations (10, 25, 50 and 100% w/w in distilled water) of the test material in order to determine (approximately) a highest non-irritating concentration and a concentration that caused minimal irritation. In this screen, both sides of the animal were shaved and sites were exposed to the various concentrations of the material; locations of the concentartions were alternated to avoid site-to-site variations; one test site had normal saline applied.
The substance was tested at 0, 10, 25, 50 and 100% w/w concentration in distilled water. There was no irritation and the 100% concentration of the test substance was seleceted for induction and challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
24 hours before first application of the test substance, and subsquently as necessary, hair was closely clipped on the right side of then animals. A dose of 0.5 ml of the freshly prepared test solution was applied to a non-adherent sterile (aproximately 6 cm2) pad coverd by hypo-allerginec cloth tape. The pad was placed on the shaved surface of the animal, and then further occluded with a latex wrap to ensure adequate contract of the test substance with the skin. The patch remained in place for six hours. At the end of the application period, extremely viscous materials were removed by gentle rinse with warm water. This induction procedure was repeated at the same site during the next 2 weeks for a total of three 6-hour exposures. The interval between induction exposures may vary between 5 and 9 days. The animals were then left untreated for approximately 2 weeks prior to primary challenge. If a second challenge was used, animals were rested for at least one week after the primary challenge.

B. CHALLENGE EXPOSURE
2 weeks after the last induction, the animals and a naive group were challanged at a virgin site (left side) with 0.5 ml at the non-irritating concentration at each site. The test substance was applied as for induction. Reactions were scored at approximately 24, 48 and 72 hours after challenge. If there was more than minimal irritation at the virgin site or if animals were considered to have shown a possible positive reaction they were re-challenged 2 weeks later at an unused site.
Challenge controls:
A group of 5 naive animals were tested for comparison using the challenge concentration - a second naive group was tested for re-challenge if applicable.
Positive control substance(s):
no

Results and discussion

Positive control results:
not applicable

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5 ml
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No systemic overt effects were observed and no overt reduced gains in body weight were noted.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5 ml. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No systemic overt effects were observed and no overt reduced gains in body weight were noted. .
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.5 ml
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
No irritation except for transient slight patchy erythema at one site in 1 of the 5 animals.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.5 ml. No with. + reactions: 1.0. Total no. in groups: 5.0. Clinical observations: No irritation except for transient slight patchy erythema at one site in 1 of the 5 animals..
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.5 ml
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: 0.5 ml. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.5 ml
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: 0.5 ml. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
0.5 ml
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading:
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0.5 ml
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading:

Applicant's summary and conclusion