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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 30, 2008 - February 20, 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD TG 404 and in accordance with the principles of GLP.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
U.S. EPA Health Effects Test Guidelines, OPPTS 870.2500 (1998), JMAFF 12-Nouan-8147, November 2000, Official Journal of the European Communities. Methods for the Determination of Toxicity, Part B.4 (Skin Irritation), Directive 2004/73/EC, 29 April 2004.
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Diethylene glycol mono phenyl ether
- Physical state: Liquid
- Analytical purity: No Certificate of Analysis; Gas Chromatogram indicates 99.5% by area DiEPh
- Lot/batch No.: 200602920-11
- Expiration date of the lot/batch: February 19, 2009
- Stability under test conditions: Test substance was expected to be stable for the duration of testing.
- Storage condition of test material: Stored at Ambient (+18 to +36°C)

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Toxicology, Department of Safety Assessment, Advinus Therapeutics Private Limited, Bangalore 560 058, INDIA
- Age at study initiation: 4-5 months
- Weight at study initiation: 2.21 to 2.31 kg
- Housing: The rabbits were housed individually in rabbit cages (approx. size: L 65 x B 65 X H 45 cm) with Noryl shallow cage body and noryl perforated raised shelf for enrichment and facilities for pelleted food (Stainless steel feed hopper) and drinking water (750 ml markrolon bottle fitted with sipper tube). The litter collection tray (noryl waste tray) were washed daily with water (except on sundays).
- Diet (e.g. ad libitum): The animals were offered rabbit feed (Nutrilab® ) manufactured by Tetragon Chemie Pvt. Ltd, KHB Industrial Area, Yelahanka New Town, Bangalore-560 064.
- Water (e.g. ad libitum): The animals were provided deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier manufactured by Eureka Forbes Ltd., Mumbai - 400 001, INDIA.
- Acclimation period: One rabbit (RB6923) was acclimatized for fourteen days while the other two (RB6924 and RB6925) rabbits were acclimatized for fifteen days under laboratory conditions after physical examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22°C
- Humidity (%): 30-70%
- Air changes (per hr): 12-15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hour light and 12 hour dark cycle

Test system

Type of coverage:
occlusive
Preparation of test site:
other: Clipped with an electric clipper
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml


Duration of treatment / exposure:
4 hours
Observation period:
Rabbit used for the single animal test was observed for a period of 96 hours (skin reaction scores were recorded only through 72 hours post application) and the additional two rabbits used in the confirmatory test were observed up to 72 hours post removal of the test patch.
Number of animals:
3 female rabbits
Details on study design:
TEST SITE
Five-tenths of a milliliter (0.5 ml) of liquid test material was placed on the dose site and covered with a gauze pad of size approximately 6 cm2 (2 x 3 cm -6ply). A control patch blank gauze pad was applied 3 – 4 cm anterior to the 4 hour test patch. All the patches were secured to the body of the animal by an adhesive tape and the entire trunk of each animal was then wrapped with non-irritating crepe elastic tape to avoid dislocation of the patch. Animals were exposed to thetest substance for a period of 4 hours. Elizabethan collars were placed on each rabbit for the designated exposure period.

REMOVAL OF TEST SUBSTANCE
The patches were removed after four hours and the applied area was wiped with water. The skin was assessed immediately after removal of the 4 hours test patch for severe irritation / corrosion. The results indicated that the test item was not irritant or corrosive to the skin. The rabbit was restrained using Elizabethan collar for 28 hours post application of the test patch.

SCORING SYSTEM:
Following the exposure period, the patches were removed and the application sites were wiped with water to remove any residual test substance. The 4 hour dose sites was examined for signs of erythema and edema within 30-60 minutes and at intervals of approximately 24, 48 and 72 hours after patch removal according to the "Primary Skin Irritation Scoring System" developed by Draize. Individual scores were recorded for each rabbit.

Results and discussion

In vivo

Results
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
There were no skin reactions observed at 1, 24, 48 and 72 hours post removal of the test patch.
Other effects:
There were no toxic signs and pre-terminal deaths during the course of the experiment. The body weights of all the rabbits increased slightly through the observation period.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results, there was no evidence of dermal irritation as evidenced by erythema and edema score of ‘0’ was observed at all the observation time points, hence classified as not irritating to skin.
Executive summary:

The acute dermal irritation/corrosion study in New Zealand White Rabbits was conducted to evaluate the skin irritation potential of Diethylene glycol mono phenyl ether.

Five-tenths of a milliliter (0.5 ml) of the undiluted test item was applied to the dose site and covered with a gauze pad of size approximately 6 cm2 (2 x 3 cm -6ply). A control patch blank gauze pad was applied 3 – 4 cm anterior to the 4-hour test patch. All patches were secured to the body of the animal by an adhesive tape and a crepe bandage wrapped around the torso of the animal. After 4 hours contact period the bandage was removed and the dose sites were wiped with water.

The degree of irritation was evaluated and scored by Draize’s evaluation method at 1, 24, 48 and 72 hour post removal of the test patch. There was no evidence of dermal irritation as evidenced by erythema and edema score of ‘0’ was observed at all the observation time points.

There were no toxic signs, pre-terminal deaths and no skin reactions observed. There were no abnormalities detected at necropsy.