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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:
1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-study according to OECD guideline 406.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EPA OTS 798.4100 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
other: MAFF Dermal Sensitization Study, 1985.
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Type of study:
Buehler test

Test material

Constituent 1
Chemical structure
Reference substance name:
1-phenoxypropan-2-ol
EC Number:
212-222-7
EC Name:
1-phenoxypropan-2-ol
Cas Number:
770-35-4
Molecular formula:
C9H12O2
IUPAC Name:
1-phenoxypropan-2-ol
Constituent 2
Reference substance name:
1-phenylpropan-2-ol
EC Number:
211-821-0
EC Name:
1-phenylpropan-2-ol
Cas Number:
698-87-3
IUPAC Name:
1-phenylpropan-2-ol
Details on test material:
Identity: Dowanol-PPh (1-phenoxy-2-hydroxypropane or propylene glycol phenyl ether)
CAS # 770-35-4 (also 41593-38-8)
Batch No.: LE08011T01
Purity: 93.7%
Supplied as: Not reported
Appearance: 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 Breeding Laboratories
- Age at study initiation: approximately 58 days
- Weight at study initiation: not specified
- Housing: Animals were housed five per cage.
- Diet (e.g. ad libitum): The animals were supplied with Purina Certified Guinea Pig Chow #5026 obtained from the Purina Mills Inc., St. Louis, Missouri ad libitum.
- Water (e.g. ad libitum): The animals were supplied with tap water ad libitum.
- Acclimation period: atleast one week prior to study start

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity (%): 40-70%
- Air changes (per hr): 15 times/hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark photocycle

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.4 ml of neat Dowanol PPh
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.4 ml of neat Dowanol PPh
No. of animals per dose:
20 treatment group + 10 control group
Details on study design:
RANGE FINDING TESTS: A preliminary skin irritation screen was conducted in order to determine a slightly irritating dose, if obtainable, as well as to establish the highest non-irritating concentration of the test material. Guinea pigs were clipped free of hair on the left and right side, and on their back, the day prior to dosing. Single applications of 0.4 ml of neat DOWANOL PPh, or applications of 0.1%, 0.5%, 1%, 5%, 10%, 25%, 50% or 75% dilutions of
DOWANOL PPh Glycol Ether in 0.5% Methocel* were topically applied to the skin of guinea pigs for six hours in Hill Top Chambers (25 mm Hill Top Chamber, Hill Top Research Inc., Cincinnati, Ohio). Two animals per dilution were used for the screen phase. An aliquot of neat DOWANOL PPh or an aliquot of a DOWANOL PPh dilution was placed in the chamber and applied to the animal. The following morning the application sites were depilated. Approximately five to six hours after depilation, the dermal test sites were graded for erythema and edema. Skin irritation readings were recorded approximately 24 and 48 hours after test material removal. Multiple animals were used to determine that 0.4 ml of neat DOWANOL PPh did not cause any irritation in screen animals and would, therefore, be used for the induction and challenge applications.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: one (A single 0.4 ml aliquot of neat Dowanol PPh was applied in Hill Top Chambers to the left side of 10 male guinea pigs
- Site: The left side of ten guinea pigs per treatment group were clipped free of hair the day prior to dosing.
- Frequency of applications: single at weekly intervals for a total of 3 consecutive weeks
- Duration: single at weekly intervals for a total of 3 consecutive weeks
- Concentrations: 0.4 ml of neat Dowanol PPh
The left side of ten guinea pigs per treatment group were clipped free of hair the day prior to dosing. A single 0.4 ml aliquot of neat DOWANOL PPh was applied in Hill Top Chambers to the left side of ten male guinea pigs. The chambers were secured with Vetrap® which was held in place with Elastikon™ and removed after approximately a sixhour exposure period. The application site was washed with tap water moistened disposable towels. Observations for erythema/edema were recorded the following day. The animals were clipped and the respective groups were treated with the test material in the same manner at weekly intervals for a total of three consecutive weeks.


B. CHALLENGE EXPOSURE
- No. of exposures: single
- Day(s) of challenge: Approximately two weeks after the last induction application
- Exposure period: 6 hours
- Test groups: same as in induction phase. Also, five naive animals were dosed with a single 0.4 ml aliquot of neat DOWANOL PPh
- Site: Approximately two weeks after the last induction application, the right side of each animal was clipped free of hair. A single 0.4 ml aliquot of neat DOWANOL PPh, a non-irritating dose, was applied to the right side of the guinea pigs in the same manner as in the induction phase.
- Concentrations: single 0.4 ml aliquot of neat DOWANOL PPh
- Evaluation (hr after challenge): approximately 24 and 48 hours after the challenge application
Approximately two weeks after the last induction application, the right side of each animal was clipped free of hair. A single 0.4 ml aliquot of neat DOWANOL PPh, a non-irritating dose, was applied to the right side of the guinea pigs in the same manner as in the induction phase. Also, five naive animals were dosed with a single 0.4 ml aliquot of neat DOWANOL PPh. The test material was removed after approximately a six-hour exposure period and the application site was washed with tap water moistened disposable towels. The following day the challenge application sites were depilated approximately five to six hours prior to scoring. The application sites were observed and graded for sensitization response or irritation approximately 24 and 48 hours after the challenge application.
Challenge controls:
not applicable
Positive control substance(s):
yes
Remarks:
Results of the AHCA and DNCB positive control study were appended to the study report (Refer to attachments)

Study design: in vivo (LLNA)

Vehicle:
other: not applicable
Concentration:
not applicable
No. of animals per dose:
not applicable
Details on study design:
not applicable
Positive control substance(s):
other: not applicable
Statistics:
Means and standard deviations were calculated for body weights. The data were evaluated for statistical outliers by a sequential test, however, outliers were not routinely excluded from statistical analysis.

Results and discussion

Positive control results:
Refer to attachment

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.4 ml of 100% DOWANOL PPh
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no clinical signs of toxicity noted
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.4 ml of 100% DOWANOL PPh. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no clinical signs of toxicity noted.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.4 ml of 100% DOWANOL PPh
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no clinical signs of toxicity noted
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.4 ml of 100% DOWANOL PPh. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no clinical signs of toxicity noted.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: not applicable
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: not applicable

Any other information on results incl. tables

none

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of the study, Dowanol PPh did not cause contact hypersensitivity when tested in guinea pigs and hence classified as not sensitizing
Executive summary:

DOWANOL PPh Glycol Ether, 94.0% purity, was evaluated for dermal sensitization potential using the Buehler method. Twenty male Hartley albino guinea pigs received three single dermal applications of 0.4 ml of neat DOWANOL PPh Glycol Ether at weekly intervals during the three-week induction period and during the challenge period. Ten naive animals also received 0.4 ml of neat DOWANOL PPh during the challenge phase. The condition of the test sites was assessed approximately 24 and 48 hours after the challenge application. Challenge application with 0.4 ml of neat DOWANOL PPh did not cause any irritation in any of the induced animals 24 or 48 hours after the challenge dose. No irritation was observed on any of the naive animals. All animals were in apparent good health and gained body weight over the duration of the study. Therefore, under the conditions of this study, DOWANOL PPh did not cause delayed contact hypersensitivity in guinea pigs.