Z-109

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in accordance with recognised guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

yes

Remarks:

Not considered to affect study validity

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

yes

Remarks:

Not considered to affect study validity

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Substance type: UVCB
- Physical state: liquid
- Analytical purity: ~90%
- Lot/batch No.: CM71217681
- Expiration date of the lot/batch: 27-Apr-2010
- Stability under test conditions: Unknown; is excluded from the statement of compliance.
- Storage condition of test material: At room temperature (range of 20 ± 5 °C), light protected.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V. Kreuzelweg 53
- Age at study initiation: 11 weeks
- Weight at study initiation: 177.5 g – 199.5 g
- Fasting period before study: overnight fasting period prior to intubation and approximately 3-4 hours post dose
- Housing: Suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C to 25°C
- Humidity (%): 30 – 70%
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 hours continuous light/dark.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE: Polyethylene glycol 300 (PEG 300)
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 ml/Kg
- Justification for choice of vehicle: NDA
- Lot/batch no. (if required): S60502-099
- Purity: NDA



DOSAGE PREPARATION (if unusual): NDA


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: the highest recommended dose in OECD 423 guidance.

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 females/group, two groups in total.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs observed daily, body weights measured on days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight no further details available

Statistics:

An estimate of the acute oral median lethal dose (LD50) of the substance was made using the mortality data obtained.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical signs were observed during the course of the study.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Other findings:

- Organ weights: No Data Available
- Histopathology: No Data Available
- Potential target organs: No Data Available
- Other observations:No Data Available

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose after single oral administration of the test substance to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight

Executive summary:

Two groups, each of three female RccHan:WIST (SPF) rats, were treated with the test substance by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was formulated in PEG 300 at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs during the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded during the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15.

All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period.

No clinical signs were observed during the course of the study.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were recorded at necropsy.

The median lethal dose after single oral administration of the test substance to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight