Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01/2009-03/2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-study according to OECD guideline 402

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)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The test substance, identified as Dowanol™ TPnB-H Glycol Ether, Lot #WK191920K1, was received on January 13, 2009 and was further identified with EPSL Reference Number 090113-1D. The test substance was stored at room temperature. The sample was administered as received.
The following information related to the characterization of the test substance was provided by the Sponsor:
Physical Description: Brown liquid
Solubility: Estimated solubility in water <5%
Stability: Test substance was expected to be stable for the duration of testing.
Expiration Date: December 19, 2010

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: received from Harlan, Indianapolis, IN on January 6, 2009.
- Age at study initiation: young adult (10 weeks)
- Weight at study initiation: males 195-208 grams and females 133-138 grams at experimental start
- Fasting period before study: not applicable
- Housing: the animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C
- Humidity (%): 14-53%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area and the trunk
- % coverage: 2 inches x 3 inches (approximately 10% of the body surface)
- Type of wrap if used: gauze pad wrapped with 3-inch Durapore tape

REMOVAL OF TEST SUBSTANCE
After 24 hours of exposure to the test substance, the pads were removed and the test sites were gently cleansed with a 95% ethanol followed by tap water and a clean paper towel to remove any residual test substance.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): pure liquid
- Constant concentration used: yes
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
Individual body weights of the animals were recorded prior to test substance application (initial) and again on Days 7 and 14 (termination).

The animals were observed for mortality, signs of gross toxicity, and behavioral changes during the first several hours after application and at least once daily thereafter for 14 days. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory,
autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

All rats were euthanized via CO2 inhalation at the end of the 14-day observation period. Gross necropsies were performed on all animals. The external surface of the body and all orifices, tissues, and organs of the thoracic and abdominal cavities were examined.
Statistics:
no data

Results and discussion

Preliminary study:
not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
0/6 (no death occurred during this study)
Clinical signs:
There were no signs of gross toxicity, dermal irritation, adverse toxicologic effects, or abnormal behavior.
Body weight:
All animals showed normal body weight gain throughout the 14-day observation period.
Gross pathology:
No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.
Other findings:
none

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the single dose acute dermal LD50 of Dowanol TPnB-H Glycol Ether was greater than 2,000 mg/kg of body weight in male and female rats.
Executive summary:

An acute dermal toxicity test was conducted with Fischer 344 rats to determine the potential for Dowanol TPnB-H Glycol Ether to produce toxicity from a single topical application. Under the conditions of this study, the single dose acute dermal LD50 of the test substance was greater than 2,000 mg/kg of body weight in male and female rats. Two thousand milligrams of the test substance per kilogram of body weight was applied to the skin of ten healthy rats for 24 hours. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days. Body weights were recorded prior to application and again on Days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice. All animals survived exposure to the test substance, gained body weight and appeared active and healthy during the study. There were no signs of gross toxicity, dermal irritation, adverse toxicologic effects, or abnormal behavior. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14- day observation period.