[(butoxymethylethoxy)methylethoxy]propan-1-ol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was carried out under GLP and in conformity with the OECD guideline for Testing of Chemicals No.401: "Acute oral toxicity".

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

[(butoxymethylethoxy)methylethoxy]propan-1-ol

EC Number:

259-910-3

EC Name:

[(butoxymethylethoxy)methylethoxy]propan-1-ol

Cas Number:

55934-93-5

Molecular formula:

C13H28O4

IUPAC Name:

1-[2-(2-butoxy-1-methylethoxy)-1-methylethoxy]propan-1-ol

Details on test material:

- Name of test material (as cited in study report): Dowanol TPnB
-Chemical name: Tripropylene glycol n-butyl ether
- Physical state: Colourless liquid
- Analytical purity: 99%
- Lot/batch No.: May '87
- Specific gravity: 0.92
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions: Estimated to be min. 2 years under these conditions
- Storage condition of test material: At ambient temperature in the dark
- Solubilityin water: 3%
- Vapor pressure : <0.01 mmHg/20°C
- Boiling point: >274°C
- Freezing point: <75°C

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, SPF- quality, randomly bred
- Age at study initiation: 11 weeks old
- Fasting period before study: 3-4 hours
- Housing:Polycarbonate cages containing purified sawdust as bedding material.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum):Ad libitum
- Acclimation period:5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23°C
- Humidity (%): 65-85°C
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs/light

Pilot study
IN-LIFE DATES: From: 18-08-1987 To:25-08-1987

Main study
IN-LIFE DATES: From: 02-09-1987 To:16-09-1987

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

VEHICLE

MAXIMUM DOSE VOLUME APPLIED:

Dose range finding: 5000mg/kg
Main study: 4200 mg/kg


DOSAGE PREPARATION (if unusual): The dose volume (ml/kg body weight) was calculated as follows;

Dosis: g/kg body weight/specific gravity in (g/ml). The specific gravity used was 0.09284 g/ml.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on the toxicity observed in the dose range finding investigation three groups of animals, each comprising 5 males and 5 females, were dosed with a single oral dose of the test substance at 2400, 3200 and 4200 mg/kg body weight, respectively.

Doses:

single dose of 2400, 3200, and 4200 mg/kg bw

No. of animals per sex per dose:

30

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology.

Statistics:

Established statistical procedure (e.g. Finney,1971)

Results and discussion

Preliminary study:

Three groups of animals, each comprising 1 male and 1 female, were dosed with a single oral dose of the test substance at 2500, 4000 and 5000 mg/kg body weight, respectively. Both animals of the 4000 mg/kg and 5000 mg/kg dose groups died with in 24 hours of dosing. Symptoms of toxicity were ataxia, lethargy, tremors, convulsions, unreactive, piloerection and abnormal respiration (i.e., dyspnoea, bradypnoea, rattled respiration). Animals of the low dose group showed as of day 3 no more signs of toxicity. The observation period was 7 days.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 800 mg/kg bw

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

3 100 mg/kg bw

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

2 600 mg/kg bw

Mortality:

The incidence of mortalities for the sexes combined from low to high dose group was 3, 6 and 10. All deaths occured within 24 hours of dosing.

Clinical signs:

other: Major signs of toxicity were lethargy, ataxia, convulsions, tremors and unreactiveness. For surviving animals these signs were reversible since as of day 2 no more significant abnormalities were observed during the 14-day observation period.

Gross pathology:

Macroscopic examination of animals at necropsy revealed bloody nose, bloody eye encrustation, moist eyes, red patches in the glandular part of the stomach and in the pancreas, petechiae of the stomach and the thymus, bloody contents or haemorrhage of the small intestine, haemothorax and dark red lungs.

Any other information on results incl. tables

The incidence of mortalities for the sexes combined from low to high dose group was 3, 6, and 10. All deaths  occurred within 24 hours of dosing. Major signs of toxicity were lethargy, ataxia, convulsions, tremors and 

unreactiveness. For surviving animals these signs were reversible since as of day 2 no more abnormalities were 

observed during the 14-day observation period. Major macroscopic abnormalities of animals at necropsy  were bloody nose, bloody eye encrustation, red patches in the glandular part of the stomach and in the

 pancreas, petechiae of the stomach and the thymus, bloody contents or haemorrhage of the small intestine, haemothorax and dark red lungs.

The LD50-value of DOWANOL TPnB for the sexes combined amounted to 2.8 g/kg body weight, whereas the LD50-values
for the sexes separately were 3.1 and 2.6 g/kg for males and females, respectively.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 value for the sexes combined amounted to 2.8 g/kg body weight, whereas the LD50 values for the sexes separately were 3.1 and 2.6 g/kg for males and females, respectively.

Executive summary:

The purpose of the study was to obtain information on the toxicity of the test substance when administered to rats in a single oral dose. Furthermore, the study was intended to derive the LD50. The study was conducted according to OECD guideline 401.

Three groups of 5 male and 5 female, young adult rats of wistar strain were used to access the acute toxicity study of Tripropylene glycol n-butyl ether. Animals were fasted overnight prior to dosing until 3 -4 hours after administration of the test substance.The undiluted test substance was administered once only by gavage at a dose level of 2400, 3200 and 4200 mg/kg body weight respectively.

The incidence of mortalities for the sexes combined from low to high dose group was 3, 6 and 10. All deaths occurred within 24 hours of dosing. Major signs of toxicity were lethargy, ataxia, convulsions, tremors and unreactiveness. For surviving animals these signs were reversible since as of day 2. No more significant abnormalities were observed during the 14 day observation period. All surviving animals showed body weight gain during the study period.

Macroscopic examination of animals at necropsy revealed bloody nose, bloody eye encrustation, moist eyes, red patches in the glandular part of the stomach and in the pancreas, petechiae of the stomach and the thymus, bloody contents or haemorrhage of the small intestine, haemothorax and dark red lungs.

The LD50 value for the sexes combined was calculated to be approximately 2800 mg/kg body weight. The LD50 values for the sexes separately were 3100 and 2600 mg/kg for males and females, respectively.