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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
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 402 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 402 (Acute Dermal Toxicity)
Version / remarks:
U.S. EPA Health Effects Test Guidelines, OPPTS 870.1200 (1998), JMAFF 12-Nouan-8147, November 2000, Official Journal of the European Communities. Methods for the Determination of Toxicity, Part B.3 (Acute Toxicity Dermal), Directive 2004/73/EC, 29 April 2
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 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: 19-Feb-2009
- Stability under test conditions: Test substance was expected to be stable for the duration of testing.
- Storage condition of test material: Ambient (+18 to +36°C)
- Solubility in water/Miscibility : 3% wt.
- pH : 3.5 – 7.5 (3% aq. Soln)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
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: 10 – 11 weeks
- Weight at study initiation: Males : 272 to 279 g, Females: 209 to 214g
- Housing: Rats were housed individually in standard polysulfone cages (Size: approximately L 425 x B 266 x H 175 mm), with stainless steel top grill having facilities for pelletted food and drinking water. Bedding: steam sterilized clean paddy husk was used and changed along with the cage twice a week.
- Diet (e.g. ad libitum): Ssniff rats/mice pellet food - maintenance meal - low in germs manufactured by Ssniff Spezialdiäten GmbH., Ferdinand- Gabriel-Weg 16, D-59494 SÖest, Germany , was provided to the animals.
- Water (e.g. ad libitum): Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cumpurifier manufactured by Eureka Forbes Ltd., Mumbai - 400 001, India, was provided to animals in polycarbonate bottles with stainless steel sipper tubes.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 12 - 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Approximately 24 hours prior to treatment, the hair on the dorsolateral thoracic surface of the skin was clipped (approximately 8 x 10 cm) with an electric clipper (Aesculap® - Germany).

Doses were calculated based on individual body weight, the undiluted test item at the dose of 5000 mg/kg body weight (A volume of 4.5 ml/kg bodyweight) was applied directly to the prepared skin of the animal, taking care to spread the substance evenly over the entire dose area, and covered with a cotton gauze (size: 9 x 5 cm of 6 ply for males and 8 x 5 cm of 6 ply for females) and secured in position by adhesive tape wound around torso. The test item contact period with the skin was for 24 hours.

After the 24-hour contact period, the patches were removed and the application site was wiped with water using clean towels to remove any residual test substance.
Duration of exposure:
24 hours
Doses:
5000 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: four times on the test day one (at hourly intervals after application) and once daily during days 2 - 15.
Weighing: Individual body weights of animals were recorded on test days 1 (Pre-application), 8 (7 days post application) and 15 (14 days post application).
- Necropsy of survivors performed: yes
Statistics:
None

Results and discussion

Preliminary study:
An initial dose of 5000 mg/kg was applied. This dose level did not produce test substance related mortality, hence, no additional dose levels were tested.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no pre-terminal deaths in any of the treated rats.
Clinical signs:
There was no Clinical/ toxic signs observed in any of the treated rats
Body weight:
All rats had gained bodyweight through the observation period.
Gross pathology:
There were no local skin reactions and no abnormality detected at necropsy.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results, the acute dermal LD50 of Diethylene glycol mono phenyl ether in Wistar rats is greater than 5000 mg/kg body weight.
Executive summary:

The acute dermal toxicity of Diethylene glycol mono phenyl ether was tested in male and female Wistar rats.

Based on the individual body weight, the undiluted test item at the dose of 5000 mg/kg body weight (a volume of 4.5 ml/kg bodyweight) was applied directly to the prepared skin of the animal, taking care to spread the substance evenly over the entire dose area, and covered with a cotton gauze (size: 9 x 5 cm of 6 ply for males and 8 x 5 cm of 6 ply for females) and secured in position by adhesive tape wound around torso. The test item contact period with the skin was for 24 hours. After 24 hour contact period with the skin, the unabsorbed test item at the site of application was removed by wiping with water and the rats were observed for 15 days. There were no toxic signs, local skin reactions and pre-terminal deaths. There were no abnormalities detected at necropsy.

Based on the above results it is concluded that the LD50 of Diethylene glycol mono phenyl ether is greater than 5000 mg/kg bodyweight.