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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
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 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
up-and-down procedure
Limit test:
no

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 confidential 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:
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: 8-12 weeks
- Weight at study initiation: 157-170g
- Fasting period before study: feed alone was withdrawn over-night (approximately 15 to 18 hours) prior to dosing. Following dosing, feed was withheld for a further period of 3 hours
- Housing: standard polypropylene rat cages with stainless steel top grills; the cages were autoclaved; gamma irradiated corn cobs was used as the bedding material; animals were housed individually.
- Diet (e.g. ad libitum): standard gamma irradiated 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 experiment in the test room

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 20.2 and 22.1°C
- Humidity (%): between 57.8 and 64.6%
- Air changes (per hr): not provided
- Photoperiod (hrs dark / hrs light): 12 hours dark/ 12 hours light

IN-LIFE DATES: From: 2011-08-04 To: 2011-09-10

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: variable
- Amount of vehicle (if gavage): 10 ml/kg b.w.
- Justification for choice of vehicle: -
- Lot/batch no. (if required): -
- Purity: -

MAXIMUM DOSE VOLUME APPLIED:

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: -
Doses:
Initial dose: 175 mg/kg b.w.
Next doses: 550 mg/kg b.w.; 2000 mg/kg b.w.
No. of animals per sex per dose:
175 mg/kg b.w.: 1 female
550 mg/kg b.w.: 3 females
2000 mg/kg b.w.: 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on day 0, day 7 and day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, morbidity/mortality
Statistics:
The LD50 was calculated using the software AOT425 StatPgm downloaded from EPA's internet website http://www.epa.gov/oppfead1/harmonization

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
1 098 mg/kg bw
Based on:
test mat.
95% CL:
> 550 - < 2 000
Mortality:
No mortality/morbidity was observed in animals treated with 175 mg/kg b.w. (animal number 14247) and 550 mg/kg b.w. (animal numbers 14248,14250 & 14252) during the entire observation period. Animal number 14249, 14251 & 14367 treated with 2000 mg/kg b.w. died on day 2 after test substance administration
Clinical signs:
The animal number 14249, 14251 & 14367 treated with 2000 mg/kg b.w. exhibited dullness upto day 1. These animals exhibited clinical signs of toxicity such as piloerection at 3, 4hr and day 1 and discharge of blood from anus was observed on day 1 and thereafter mortality was observed on day 2 after test substance administration. Initial animal 14247 treated with test substance at 175 mg/kg b.w. and animal number 14248, 14250 & 14252 treated at 550 mg/kg b.w. did not exhibited any clinical signs of toxicity and mortality during the entire observation periods.
Body weight:
All the survivor animals showed normal body weight during experimental period.
Gross pathology:
Gross pathology examination conducted at the end of the experiment on all survivor animals as well as the animals died during the test did not reveal any macroscopic lesions.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
On the basis of the above results, the estimated acute oral LD50 of Proviplast (bis(2butoxyethyl)adipate) determined was 1098 mg/kg b.w. (based on assumed sigma of 0.5). Approximate 95% confidence interval is 550 to 2000 mg/kg b.w.
Executive summary:

Acute oral toxicity of Proviplast 0142, bis(2 -butoxyethyl)adipate, was tested in female Wistar rats according to OECD guideline (No. 425).

Dosing mixed in corn oil, was performed as a single oral gavage dose to one female animal at dose level of 175 mg/kg b.w. and three female animals (one at a time) at a dose level of 550 mg/kg b.w. These animals did not exhibit clinical signs of toxicity and mortality, hence antother three animals (one at a time according to up and down method) were administered 2000 mg/kg b.w. These animals exhibited dullness, piloerection and discharge of blood from anus and died on day 2. Since the stopping criteria were met, dosing was stopped as recommended by the guideline.

Following dosing, the surviving rats were observed for 14 days for mortality and clinical signs of toxicity. Body weights of all survived animals were noted weekly. A gross necropsy was performed on all animals found dead during the study and on all survivors on day 14. Weekly body weight was normal. Gross pathology of animals dit not reveal any macroscopic lesions.

On the basis of the above results, the estimated acute oral LD50 of Proviplast 0142, bis(2 -butoxyethyl)adipate, dertermined was 1098 mg/kg b.w. Approximate 95% confidence interval is 550 to 2000 mg/kg b.w.