Reaction product of propylene and synthesis gas in a hydroformylation being a sidestream during purification

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

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:

Reference substance 001

EC Number:

920-427-4

Details on test material:

- Name of test material (as cited in study report): Zorgol 48
- Substance type: UVCB substance
- Physical state: orange liquid
- Analytical purity: not applicable
- Lot/batch No.: 20100223161335
- Code number: PH-10/0131
- Expiration date of the lot/batch: 2011-02-09
- Stability under test conditions: no data
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevange JANVIER (53940 Le Genest St. Isle, France)
- Age at study initiation: 8 weeks
- Weight at study initiation: 172 - 204 g
- Fasting period before study: yes
- Housing: in groups of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid containing sawdust bedding
- Diet (e.g. ad libitum): M20-SDS, ad libitum
- Water (e.g. ad libitum): tap water from public distribution system, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25°C
- Humidity (%): 30 - 70%
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12 /12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: no vehicle

MAXIMUM DOSE VOLUME APPLIED: 2.23 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no data

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Six female Sprague Dawley rats

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation 0.5, 1, 3, and 4 hours after administration, daily thereafter; weighing at day 0C before administrationof test substance then at day 2, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: highest dose tested

Mortality:

No mortality was observed during the study.

Clinical signs:

other: Observations at first day of the test: decrease in spontaneous activity (3/6 and muscle tone (2/6), piloerrection (3/6), staggering gait (3/6). After 24 h all animals recovered normal behaviour.

Gross pathology:

No treatment related effects were observed by macroscopical examination of the animals at the end of the study.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test item Zorgol 48 is higher than 2000 mg/kg body weight by oral route in the rat.
In accordance with the OECD guideline n°423, the LD50 cut-off of the test item may be considered higher than 5000 mg/kg body weight by oral route in the rat.

Executive summary:

An acute oral toxicity study was performed using the acute toxic class method according to OECD test guideline 423. Groups of three fasted female Sprague-Dawley rats for each of step 1 and step 2 were given a single oral dose of the test item Zorgol 48 as such by gavage at a dose of 2000 mg/kg bw. Test animals were observed for 14 days.

 

No mortality was noticed following administration of this dose at step 1 and 2. Clinical findings were only noted at the first day (decrease in spontaneous activity and muscle tone - 3 and 2 of 6 animals respectively, piloerrection - 3 of 6 animals, staggering gait - 3 of 6 animals). After 24 hours all animals recovered normal behaviour. Development of body weight was found to be normal. Necropsy did not reveal any findings.

 

The oral LD50 of Zorgol 48 is higher than 2000 mg/kg bw in the rat (Colas/Laus, 2010).

In accordance with OECD TG 423, the LD50 cut-off of Zorgol 48 may be considered higher than 5000 mg/kg bw. Zorgol 48 is of low acute oral toxicity.

 

This oral toxicity study is acceptable and satisfies the guideline requirement for an oral toxicity test (OECD423) in rats.