2,3-Epoxypropyl neodecanoate, oligomeric reaction products with phosphorous acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004-07-05 to 2004-07-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,3-Epoxypropyl neodecanoate, oligomeric reaction products with phosphorous acid

EC Number:

500-336-2

EC Name:

2,3-Epoxypropyl neodecanoate, oligomeric reaction products with phosphorous acid

Cas Number:

157348-58-8

Molecular formula:

Exact identification is not feasible

IUPAC Name:

Copolymer of neodecanoic acid oxiranylmethyl ester and phosphorous acid

Test material form:

liquid

Details on test material:

Copolymer of neodecanoic acid oxiranylmethyl ester and phosphorous acid, manufactured by Degussa GmbH, Batch: 413250

Specific details on test material used for the study:

PREPARATION of the TEST ITEM
- In the first and second step 2000 mg of the test item were diluted in Cottonseed Oil (Sigma Chemicals Co., Lot 103K0064) ad 10 mL.
- The test substance was freshly mixed prior to administration and stirred troughout dose administration to guarantee stability and homogenicity.
The vehicle was chosen due to its non-toxic characteristics.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rats (HsdBrlHan: WIST), Sex: female
- Step 1: Body weight at the commencement of the study: 150 - 153 g
Step 2: Body weight at the commencement of the study: 140 - 165 g
- Three female animals were used for each step
- The animals were derived from a controlled full barrier maintained breeding system (SPF)
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- According to Art. 9.2, No.7 of the Greman Act on Animal Welfare the animals were bred for experimental purposes.

ANIMAL HUSBANDRY
The animals were barrier maintained (semi-barrier) in an air conditioned room
- Temperature: 22 +/- 3 °C
- Rel. humidity: 55 +/- 10%
- Artificial change: 10 x / hour
- Feeding ad libitum, Altromin 1324 maintenance diet for rats and mice, totally-pathogen-free (TPF)
- Free access to tap water (drinking water, municipal residue control, microbiol. controlled periodically)
- The animals were kept in Macrolon cages on Altromin saw fiber bedding
- Certificates of food, water and bedding are filed at BSL Bioservice
- Adequate acclimatization period

PREPARATION OF THE ANIMALS
- The animals were marked for individual identification by tail painting
- Prior to the adminstration a detailed clinical observation was made of all animals
- Prior to administration of the test item animals were fasted by withholding food overnight.
Following the period of fasting the animals were weighed and the test item was administered. Then the food was withheld for a further 3-4 hours.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

cotton seed oil

Details on oral exposure:

ADMINISTRATION:
- The test item was aministered in a single dose by gavage using an intubation cannula.
- Volume of administration: The test item was administered according to body weight at a volume of 10 mL/kg bw.

Doses:

The starting dose (step 1 and 2) was selected to be 2000 mg/kg body weight. According to the acute toxic class method regime no further testing was required since no compound-related mortality was found.

No. of animals per sex per dose:

6 (step 1 and 2)

Control animals:

no

Details on study design:

OBSERVATION:
- Animals were observed for 14 days after dosing.

WEIGHT ASSESSMENT:
- The animals were weighed prior to the administration and once a week thereafter.

CLINICAL EXAMINATION:
- A careful clinical examination was made several times on the day of dosing. Part of this were at least three observations within the first four hours post-dose.
Animals were observed once a day thereafter.
- Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

PATHOLOGY:
- At the end of the observation period

Statistics:

EVALUATION OF RESULTS:
Individual reactions of each animal were recorded at each observation time. Toxic response data were recorded by sex and dose level. Nature, severity and duration of clinical observations were described. Body weight changes were summarized in tabular form. Necropsy findings were described.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occured.

Clinical signs:

No clinical signs of toxicity were observed throughout the observation period for any animals of step 1 and 2.

Body weight:

Throughout the 14-days observation period no weight loss was recorded in any animals of step 1 and 2 (see tables "Absolute body weights in g" below).
The weight gain was within the expected range.

Gross pathology:

Beside acute injection of blood vessels in the adominal region, which is due to the euthanasia injection no special gross pathological changes were found in any animals of step 1 nad 2.

Other findings:

No other treatment related effects were observed.

Any other information on results incl. tables

Absolute Body Weights in g

Step 1 (2000 mg/kg bw)

Animal No./Sex	Day 0	Day 7	Day 14
1 / female	150	167	182
2 / female	153	179	193
3 / female	151	182	203

Step 2 (2000 mg/kg bw)

Animal No./Sex	Day 0	Day 7	Day 14
1 / female	147	164	167
2 / female	140	160	162
3 / female	165	176	188

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study the acute toxicity after oral application is greater than 2000 mg/kg bw.

Executive summary:

In this study the acute toxic class method according to OECD 423 was performed with the test item.

In the first step the test item was given at the limit dose of 2000 mg/kg body weight to a group of 3 female rats (HsdBrlHan:WIST) as a single administration by oral gavage at the volumne of 10 mL/kg bw. In the second step the test item was given at the same dose and volume to a further group of 3 female rats (HsdBrlHan:WIST).

The dosage of 2000 mg/kg bw caused no compound-related mortality in any animals of step 1 and 2 within 14 days post-dose.

A careful cinical examination was made several times on the day of dosing. Part of this were at least three observations within the first four hours post-dose. Animals were observed once a day thereafter.

At the end of the observation period the surviving animals were sacrified. Necropsy of all animals was carried out to record gross pathological changes.

No clinical signs of toxicity were observed throughout the observation period for any animals of step 1 and 2.

Beside acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection no special gross pathological changes were found in any animals of step 1 and 2.

Throughout the 14 -days observation period no weight loss was recorded in any animals of step 1 and 2. The weight gain was within the expected range.

No other treatment related effects were observed.

Therefore, under the conditions of this study the acute toxicity after oral application is greater than 2000 mg/kg bw.