Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to GLP and state of the art and actual methods and is therefore considered reliable, relevant and adequate.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Proviplast 0142 (bis(2-butoxyethyl)adipate)
- Chemical Name: Bis(2-butoxyethyl)adipate
- Substance type: liquid
- Physical state: clear liquid with a very faint odour
- Analytical purity:98,83%
- Composition of test material, percentage of components: see Condifential details
- Purity test date: 2011-07-11
- Lot/batch No.:11701913 SA
- Expiration date of the lot/batch: 2012-12-14
- Storage condition of test material: store in tightly closed containers between -20 and +40°C

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, USA and bred at IIBAT animal house facility
- Age at study initiation: not provided
- Weight at study initiation: male: 264-272g; female: 225-254g
- Fasting period before study: not provided
- Housing: standard polypropylene rat cages with stainless steel top grill; the cages were autoclaved; gamma irradiated corn cobs were used as the bedding material, animals were housed individually
- Diet (e.g. ad libitum): standard gamma irradiated rodent pellet feed was provided ad libitum
- Water (e.g. ad libitum): reverse osmosis water was provided ad libitum
- Acclimation period: five days prior to the range finding and main experiment in the test room

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 20.2 and 22.1°C
- Humidity (%): between 58.0 and 64.3%
- Air changes (per hr): not provided
- Photoperiod (hrs dark / hrs light): 12h light/ 12h dark

IN-LIFE DATES: From: 2011-08-08 To: 2011-08-31

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: body surface area
- % coverage: approximately 10%
- Type of wrap if used: porous gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): using cotton soaked in water
- Time after start of exposure: 24 hour

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Concentration (if solution): 100% (as such)
- Constant volume or concentration used: known weight of the test substance
- For solids, paste formed: not applicable
Duration of exposure:
24hour
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
range finding study: 1 male + 1 female; 2000 mg/kg b.w.
limit test (main study): 5 males + 5 females; 2000 mg/kg b.w.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation daily for 14 days; weighing on day 0 and weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, morbidity/mortality

Results and discussion

Preliminary study:
A range finding study was carried out in order to establish the dose levels for the main study. In the range finding study to 1 male and 1 female, the test substance was applied at the dose of 2000 mg/kg b.w.. Following the application, the animals were observed for 4 days. No mortality occurred at the above dose level.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No morbidity/mortality was observed in treated group of rats throughout the observation period
Clinical signs:
No clinical signs of toxicity were observed in treated group of rats for the entire observation period. No changes were seen in fur, eyes or mucous membrane of the animals. No dermal reactions were observed at the application site.
Body weight:
All animals showed normal body weight on day 7 and 14.
Gross pathology:
Gross pathology examination conducted at the end of 14-day observation dit not reveal any macroscopic lesions.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 of Proviplast, bis(2-butoxyethyl)adipate was considered as >2000 mg/kg b.w. for Wistar Rats
Executive summary:

Acute dermal toxicity study (limit test) with bis(2 -butoxyethyl)adipate, Proviplast 0142, was performed in male and female Wistar rats at IIBAT (India) at 2000 mg/kg b.w. of test substance applied to the clipped area of 5 males and 5 females. Following application, the rats were observed for 14 days for morbidity, mortality and clinical sings of toxicity. Animals treated with the test substance did not exhibit any clinical signs of toxicity for the entire observation period. No adverse skin reactions at the site of application were observed following the removal of the test substance. No mortality and morbidity was recorded in rats throughout the observation period. Rats treated with the test substance showed normal body weight during the study. None of the animals showed any macroscopic lesions.

From the experimental results, dermal LD50 of Proviplast 0142, bis(2 -butoxyethyl)adipate, for Wistar rat was determined as > 2000 mg/kg b.w.