Reaction mass of (3R)-3-[(1R)-1-ethoxyethoxy]-3-methylpent-1-en-4-yne and (3R)-3-[(1S)-1-ethoxyethoxy]-3-methylpent-1-en-4-yne and (3S)-3-[(1R)-1-ethoxyethoxy]-3-methylpent-1-en-4-yne and (3S)-3-[(1S)-1-ethoxyethoxy]-3-methylpent-1-en-4-yne

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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Reference 2

Reference Type:

other: Amendment

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

72008-25-4

EC Number:

615-703-3

Cas Number:

72008-25-4

IUPAC Name:

72008-25-4

Details on test material:

- Name of the test substance used in the study report: Asta-C6-Acetal
- Physical state: liquid, achromatic
- Storage: refrigerator, exclusion of light

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae Gmbh, Biberach, FRG
- Age at study initiation: young adults
- Weight at study initiation: 150 - 300 g
- Fasting period before study: 16 hours
- Housing: single housing; stainless stell wire mesh cages, type DK-III (Becker & Co., Castrop-Rauzel, FRG); no bedding in the cages; sawdust in the waste trays
- Diet: ad libitum, Kliba-labordiaet 343, Klingentalmuehle AG Kaiseraugst, Switzerland
- Water: ad libitum, tap water
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes: fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Remarks:

DAB 10

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 4 and 40 g/100 mL
- Amount of vehicle: 5 mL/kg
- Justification for choice of vehicle: the test substance was insoluble in water

CLASS METHOD
- Rationale for the selection of the starting dose: based on the physical and chemical characteristics of the test substance and the composition, no pronounced acute oral toxicity was expected. Therefore a starting dose of 2000 mg/kg bw was chosen as a first step.

Doses:

200 and 2000 mg/kg

No. of animals per sex per dose:

Experiment 1 (2000 mg/kg): 3 females
Experiment 2 (200 mg/kg): 3 females
Experiment 3 (200 mg/kg): 3 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights were determined shortly before administration (day 0), weekly thereafter and at the end of the study (before fasting period). A check concerning general observations and mortality was made twice each working day and once on weekends and on public holidays.
- Necropsy of survivors performed: yes. Withdrawal of food at least 16 hours before killing with CO2; then necropsy with gross-pathological examination.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

- All animals exposed to 2000 mg/kg died, within 1 day after exposure.
- No mortality observed in animals exposed to 200 mg/kg.

Clinical signs:

other: - Female animals exposed to 2000 mg/kg: A poor general state, dyspnea, apathy, and paresis were observed in all animals, between time of exposure and 4 hours after exposure. Atonia and erythema were observed in all animals, between 1 and 4 hours after exp

Gross pathology:

- Congestion agonal was observed in all female animals exposed to 2000 mg/kg
- No pathologic findings noted in all animals exposed to 200 mg/kg

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information

Conclusions:

Under the conditions of this study the oral LD50 in Wistar rats is between 200 and 2000 mg/kg bw.

Executive summary:

In GLP-compliant EU Method B1 guideline study modified according to the acute toxic class method , 3 female Wistar rats were exposed to 2000 mg/kg bw, and 3 male and 3 female Wistar rats were exposed via oral gavage to 200 mg/kg bw of the test substance dissolved in olive oil DAB. After an observation period of 14 days the surviving animals were necropsied. Several signs of toxicity were noted in the animals exposed to 2000 mg/kg bw, all of which died within 1 day. Gross pathology showed agonal congestion in these animals. No mortality was observed in animals exposed to 200 mg/kg bw. The LD50 was therefore determined to be between 200 and 2000 mg/kg bw.