reaction products of 1,4-butanediol with 1,3-chloro-2,3-epoxypropane, esters with prop-2-enoic acid

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 1984

Deviations:

yes

Remarks:

modified according to BGA-modell: "Neue Wege zur Bestimmung der akuten Toxizitaet von Chemikalien" (1991)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of butane-1,4-diol and 1-chloro-2,3-epoxypropane, esters with acrylic acid

EC Number:

701-230-0

Cas Number:

52408-42-1

Molecular formula:

C16H26O8

IUPAC Name:

Reaction products of butane-1,4-diol and 1-chloro-2,3-epoxypropane, esters with acrylic acid

Test material form:

liquid

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, D-W7950 Biberach, FRG
- Age at study initiation: young adult
- Weight at study initiation: 176-190g
- Fasting period before study: >=16h (water ad lib.)
- Housing: individually in stainless steel wire mesh cages, type DK-III
- Diet (e.g. ad libitum): Kliba diet 343 ad lib.
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: >= 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h/12h

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2 or 20g/100ml
- Amount of vehicle (if gavage): 10ml/kg b.w.
- Justification for choice of vehicle: physiological

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 2000mg/kg b.w. was selected because no toxicity was expected based on physical and chemical characteristics of the test substance.

Doses:

200 mg/kg bw
2000 mg/kg bw

No. of animals per sex per dose:

3 females, 3 males (200 mg/kg)
3 females (2000 mg/kg)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
observations: serveral times on day one, at least once daily thereafter
weighing: once before application, weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD0

Effect level:

200 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD100

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

200 mg/kg: no deaths
2000 mg/kg: all animals died within 4-24h

Clinical signs:

other: 200 mg/kg: no symptoms 2000 mg/kg: poor general state, dyspnoea, apathy, abdominal position, atonia, paresis, cyanosis, diarrhea

Gross pathology:

200 mg/kg: no effects
2000 mg/kg: general congestion

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of this study, the LD50 was found to be greater than 200 mg/kg and less than 2000 mg/kg bw.

Executive summary:

A group of 6 fasted animals (3 males and 3 females) was given a single oral dose of test material preparation in aqua bidest at the dose level of 200 mg/kg bw. Another group of 3 females was treated in the same way with a dose of 2000 mg/kg bw.

The animals treated with 200 mg/kg bw did not show any mortality or symptoms. No abnormalities were noted at necropsy of animals sacrificed at the end of the study.

Signs of toxicity noted in females treated with 2000 mg/kg bw comprised poor general state, dyspnea, apathy, abdominal position, atonia, paresis, cyanosis and diarrhea. All females treated with 2000 mg/kg bw died 4 hours or 1 day after treatment. Necropsy findings of the animals that died was general congestion.

Under the conditions of this study, the range of LD50 after oral application was found to be greater than 200 mg/kg bw and less than 2000 mg/kg bw.