[(butoxymethylethoxy)methylethoxy]propan-1-ol

Endpoint summary

Description of key information

GLP-studies according to OECD guidelines 401 and 402 are available for tripropylene glycol butyl ether. This data is supported by non-GLP studies equivalent to OECD guidelines 401 and 402 .

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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".

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

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

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)

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.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 800 mg/kg bw

Sex:

male

Dose descriptor:

LD50

Effect level:

3 100 mg/kg bw

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 600 mg/kg bw

Quality of whole database:

Good (Klimisch 1)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was conducted under GLP and according to OECD guideline 402.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld
- Age at study initiation: 9 weeks approximately
- Weight at study initiation: Males: 349 to 398 gms and Females: 241 to 254 gms
- Housing: Rats were individually housed in polycarbonate cages
- Diet (ad libitum): Rats were supplied by standard diet RMH-B, pellet diameter 10 mm from Hope Farms, Woerden, and The Netherlands
- Water (ad libitum): Tap water
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C to 23°C
- Humidity (%): 65-95%
- Air changes (per hr):
- Photoperiod: 12hrs dark /12 hrs light


IN-LIFE DATES: From: 1987-10-02 to: 1987-10-16

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Fur from upper-dorso-lateral area of each animal was clipped to expose Approximately 10% of the total body surface area
- % coverage: Approximately 10% of the total body surface area
- Type of wrap if used: Undiluted test substance was evenly spread on surgical gauze (5×5 cm and 5×3.5 cm for males and females respectively) that was fixed to aluminum foil with a drop of Vaseline. Again with a drop of Vaseline this patch was attached to flexible bandage which was applied to clipped area of trunk of each animal and fixed with adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After 25 hours of exposure, the semi-occlusive bandage was removed and discarded and the remaining test substance on the treated surface was gently removed with tissues moistened with tap water.
- Time after start of exposure: 25 hours

Duration of exposure:

25 hours

Doses:

single dose of 2000 mg/kg bw

No. of animals per sex per dose:

5/sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Cage-side observations were performed on the day of dosing (approximately once every 2 hours) and daily thereafter, with exception weekends and holidays a mortality check was performed at the end of the day.
- Frequency of weighing: Weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Sex:

female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortalities occurred during exposure and 14 day exposure period.

Clinical signs:

other: No signs of systemic toxicity were observed during exposure and 14 day observation period.

Gross pathology:

Macroscopic examination at necropsy of all animals at the end of the study revealed no test substance related gross abnormalities.

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Based on the results of this the dermal LD0 of TPnB in male and female rats was > 2000 mg/kg.

Executive summary:

One group of Wistar rats comprising 5 males and 5 females was treated with a single dermal dose of TPnB (Tripropylene glycol n-butyl ether) colorless liquid at 2000 mg/kg body weight for 25 hours. Rats were received from Charles River Wiga GmbH, Sulzfeld and kept for acclimation period of 6 days. Rats were supplied by standard diet (ad libitum) RMH-B, pellet diameter 10 mm from Hope Farms, Woerden, and The Netherlands. Rats were provided (ad libitum) with tap water throughout the study period.

Undiluted test substance was evenly spread on surgical gauze (5×5 cm and 5×3.5 cm for males and females respectively) that was fixed to aluminum foil with a drop of Vaseline. Again with a drop of Vaseline this patch was attached to flexible bandage which was applied to clipped area of trunk of each animal and fixed with adhesive tape approximately 10% of the total body surface area.

Monitored for effects included clinical observations, body weights and gross pathology. The treated skin surface of the animals revealed no irritation. In addition, observations regarding changes of treated surface were performed following bandage removal and on 4, 7 and 14. No mortalities occurred during exposure and 14 day exposure period. No signs of systemic toxicity were observed during exposure and 14 day observation period. Weekly group mean body weight gain was normal.

All surviving animals were sacrificed by Co2 asphyxiation and subjected to necropsy. Macroscopic examination at necropsy of all animals at the end of the study revealed no test substance related gross abnormalities.

Based on the results of this the dermal LD0 of TPnB in male and female rats was > 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Good (Klimisch 1)

Additional information

Acute toxicity studies are available for the oral and dermal route and all studies are of acceptable quality (Klimisch 1 or 2).

Oral: The identified key study is the Dow/Notox-1988 study in Wistar rats administered tripropylene glycol n-butyl ether at doses of 2400, 3200 and 4200 mg/kg body weight and the LD50 (females) was 2600 mg/kg body weight, for males 3100 mg/kg body weight and the LD50 (combined) was ca. 2800 mg/kg body weight. The lowest value of 2600 mg/kg body weight will be considered for risk assessment. In the supporting studies, the LD50 was > 2000 mg/kg body weight.

Inhalation - Due to the low vapor pressure of this substance, no acute inhalation studies have been conducted (refer to study waiver).

Dermal - The identified key study is the Dow-1988 study in Wistar rats dermally exposed to a single dose of 2000 mg/kg body weight and the LD0 for both the sexes was > 2000 mg/kg body weight. In the supporting Dow-1988 study in rabbits, the dermal LD0 was > 2000 mg/kg body weight.

Justification for selection of acute toxicity – oral endpoint
GLP study in accordance with OECD TG 401

Justification for selection of acute toxicity – inhalation endpoint
Refer to study waiver

Justification for selection of acute toxicity – dermal endpoint
GLP study conducted according to OECD TG 402

Justification for classification or non-classification

The oral LD50 value for oral route is > 2000 mg/kg body weight and the dermal LD0 is > 2000 mg/kg body weight. According to the EU criteria for Classification, Labeling and Packaging (CLP) and Annex VI of the Council Directive 67/548 EEC (amended by Directive 83/467 EEC), TPnB will not be classified for acute toxicity for any route of exposure.