5,6,7-TRIMETHYLOCTA-2,5-DIEN-4-ONE

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 19 November 2003 to 05 february 2004

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

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(2E,5Z)-5,6,7-trimethylocta-2,5-dien-4-one

Cas Number:

357650-26-1

Molecular formula:

C11H18O

IUPAC Name:

(2E,5Z)-5,6,7-trimethylocta-2,5-dien-4-one

Constituent 2

Reference substance name:

(2E,5E)-5,6,7-trimethylocta-2,5-dien-4-one

Cas Number:

847144-75-6

Molecular formula:

C11H18O

IUPAC Name:

(2E,5E)-5,6,7-trimethylocta-2,5-dien-4-one

Test material form:

liquid

Specific details on test material used for the study:

Batch: 9000530064
Aspect: Slightly yellow liquid
Purity: 96.7%
Expiry date: 12-Sept-2004

Test animals

Species:

rat

Strain:

Wistar

Remarks:

HanBrl: Wist (SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd Laboratory Animal Services CH4414 Füllinsdorf Switzerland
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 168.8 - 195.0 g
- Fasting period before study: 17 - 18 hours
- Housing: In group of three in Mkrolon type-4 cages with wire mesh tops and standard softwood bedding ('Lignocel schill AG, CH-4132, Muttenz / Switzerland)
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch nos. 54/03 and 78/03 (Provimi Kliba AG, CH-4303 Kaiseraugst /Switzerland) ad libitum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum
- Acclimation period: 7 days. Under laboratory conditions, after healt examination. Only animals without any signs of illness were used for the study.
- Method of randomisation in assigning animals to test and control groups : Selected by hand at time of delivery. No computer generated randomization program.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 hours changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.05 or 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL / kg body weight
- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date.
- Lot/batch no. (if required): 448174 /121203148

MAXIMUM DOSE VOLUME APPLIED: 10 mL / kg body weight

Doses:

- 500 mg / kg bw (one group)
- 2000 mg / kg bw (two groups)

No. of animals per sex per dose:

3 females at 500mg/kg
6 females at 2000mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortalitiy / Viability: daily during acclimatization and twice daily during days 1-15.
Body weights: on test days 1 (prior to administration), 8 and 15.
Clinical signs: Daily during acclimatization and at approximately 0 (second 2000 mg/ kg treated group only), 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes
Animal which died spontaneously during the observation period was necropsied as soon as it was found dead. All surviving animals were killed at the end of the observation period and macroscopic examinations were perfomed.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One 2000 mg / kg treated animal was found dead on test day 2 after test item administration. The remaining animals treated at 2000 mg / kg and 500 mg / kg survived until the end of the study period

Clinical signs:

other: No clinical signs were observed in the 500 mg / kg treated animals during the cours of the study Slightly ruffled fur was observed in the 2000 mg/kg treated animals from the 0 or 1 to the 5 hour reading and persisted in the three animals up to test da

Gross pathology:

Reddish liquid contents was observed in the caecum of one 500 mg/kg treated animal. Congestion in the lungs and liquid contents in the stomach distented with gas were seen in one 2000 mg/kg treated animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of GR 84-2517 after single oral administration to female rats, observed over a period of 14 days is:

LD50 (rat) greater than 2000 mg/kg body weight

Executive summary:

Three groups each of three female HanBrl (SPF) rats, were treated with GR 85 -2517 by oral gavage administration at dosage of 500 or 2000 mg/kg body weight. The test item was diluted in PEG 300 at concentration of 0.05 or 0.2 g/mL and administred at a volume dosage 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 at approximately 0 (second 2000 mg/kg treated group only), 1, 2, 3, and 5 hours after treatment on day 1 and once daily during tests days 2 -15. Mortalility/viability was recorded twice daily during days 1 -15. Body weight were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

The following animals were treated and percentage of mortallity was observed:

3 females at 500 mg/kg bw 0%

6 females at 2000 mg/kg bw 17%

One 2000 mg/kg bw treated animal was found dead on test day 2 after test item administration. The remaining animals treated at 2000 mg/kg bw and 500 mg/kg bw survived until the end of the study period.

No clinical sign were observed in the 500 mg/kg bw treated animals during the course of the study.

Slightly ruffled fur was observed in the 2000 mg/kg bw treated animals from the 0- or 1- to the 5 -hours reading and persisted in three animals up to test day 6 and in a further animal up to test day 7. Hunched posture was noted from 0 - or 1- to the 5- hours reading and persisted in one animal up to test day 4 and in three further animals up to test day 6. Slight sedation was seen in one animal at the 1 -hour reading, in another animal at the 3- hour reading and in two further animals from the 0- to the 5- hours reading. Slight salivation was observed in one animal at the 1- , in two animals from 0- to the 1 -hour reading and persisted in one animal up to 2 -hours reading.

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

Reddish liquid contents was observed in the caecum on one of the 500 mg/kg treated animal. Congestion in the lungs and liquid contents in the stomach distended with gas were seen in one 2000 mg/kg treated animal.

The median lethal dose of GR-85 -2517 after single oral administration to female rats, observed over a period of 14 days is:

LD₅₀ (rat) greater than 2000 mg/kg body weight