1,4-bis(2,3-epoxypropoxy)butane

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:

guideline study

Remarks:

Well documented, according to accepted guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987 followed, reliability scoring based on OECD Guideline 423.

Deviations:

yes

Remarks:

-Source of test substance not reported; animals not observed at least once during the first 30 minutes; no individual data for signs and symptoms

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1984

Deviations:

yes

Remarks:

-Source of test substance not reported; animals not observed at least once during the first 30 minutes; no individual data for signs and symptoms

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,4-bis(2,3-epoxypropoxy)butane

EC Number:

219-371-7

EC Name:

1,4-bis(2,3-epoxypropoxy)butane

Cas Number:

2425-79-8

Molecular formula:

not applicable, UVCB

IUPAC Name:

N,N-dimethylacetamide

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): GRILONIT RV 1806.
- Physical state: Liquid.
- Analytical purity: Technical commercial quality (excluded from Statement of Compliance).
- Lot/batch No.: DC 2106.2.
- Stability under test conditions: Test article is stable for at least 1 year; test article in dilution is stable for at least 2 hours.

Test animals

Species:

rat

Strain:

other: KFM-Han. Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf / Switzerland.
- Age at study initiation: 9 weeks (males); 11 weeks (females).
- Weight at study initiation: 198 to 238 g (males); 167 to 199 g (females).
- Fasting period before study: 12 to 18 hours.
- Housing: Groups of 5 in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, 4132 Muttenz, Switzerland).
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, Batch 25/88 rat maintenance diet ("Kliba", Klingentalmuehle AG, 4303 Kaiseraugst, Switzerland), available ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen, available ad libitum.
- Acclimation period: At least 1 week under laboratory conditions, after veterinary examination.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3.
- Humidity (%): 40 to 70.
- Air changes (per hr): 10 to 15.
- Photoperiod (hrs dark / hrs light): 12 / 12.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 4% solution of carboxymethylcellulose sodium salt purum in distilled water.

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 4% solution of carboxymethylcellulose sodium salt purum in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 20 mL./kg body weight


DOSAGE PREPARATION (if unusual): The test article was placed into a glass beaker on a tared Mettler PK 300 balance, and the vehicle, was added. A weight by volume dilution was prepared using a homogenizer.

Doses:

600, 2000, and 5000 mg/kg body weight.

No. of animals per sex per dose:

5 per sex per dose.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
Mortality/Viability: 4 times during test Day 1, and daily during Days 2 to 15.
Body weights: Test Days 1 (pre-administration), 8, and 15.
- Necropsy of survivors performed: Yes.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: The animals were checked for the symptoms such as general behavior, respiration, eye, nose, motility, body posture, motor susceptibility, skin, etc.

Statistics:

The LOGIT-Model (COX, Analysis of Binary Data, London 1977) was applied to estimate the toxicity value. Additionally, the 90, 95, and 99% confidence limits for the toxicity for each sex and the slope of the dose response line were estimated.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 163 mg/kg bw

95% CL:

646.7 - 1 757

Remarks on result:

other: None

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

1 118 mg/kg bw

95% CL:

165 - 2 345

Remarks on result:

other: None

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

1 293 mg/kg bw

95% CL:

427 - 2 341

Remarks on result:

other: None

Mortality:

600 mg/kg body weight group: In males, 1 death on Day 2; no death in females.
2000 mg/kg body weight group: In males, 2 deaths at Hour 2, 1 death at Hour 3, and 1 death on Day 2; In females, 2 deaths at Hour 2, 2 deaths at Hour 3, and 1 death on Day 2.
5000 mg/kg body weight group: In males, 1 death at Hour 1, 1 death at Hour 2, 1 death at Hour 3, and 2 deaths at Hour 5; In females, 4 deaths at Hour 1, 1 death at Hour 2.

Clinical signs:

other: The following symptoms were observed: 600 mg/kg body weight: sedation, dyspnea, hunched posture, ruffled fur. 2000 mg/kg body weight: sedation, dyspnea, ataxia, ventral body position, hunched posture, spasms (males), diarrhea (males), ruffled fur. 5000 m

Gross pathology:

The following macroscopic organ changes were observed:
1) 600 mg/kg body weight group:
-Dead and sacrificed: no pathologic changes
2) 2000 mg/kg body weight group:
-Dead: lungs - not collapsed; no pathologic changes
-Sacrificed: no pathologic changes
3) 5000 mg/kg body weight group:
-Dead: lungs - not collapsed; no pathologic changes

Other findings:

No other information reported.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Information Criteria used for interpretation of results: CLP (EC 1272/2008) --> Harmful if swallowed

Conclusions:

Based on the observations, the LOGIT-estimation applied for the acute oral toxicity of the substance in rats of both sexes observed for a period of 15 days is: LD50 (rat): 1163 mg/kg bw

Executive summary:

The test article was administered to rats of both sexes by oral gavage, at doses from 600 to 5000 mg/kg bw.

The following death rate was observed: 10% at 600 mg/kg bw, 90% at 2000 mg/kg bw and 100% at 5000 mg/kg bw.

Based on these observations, the LOGIT-estimation applied for the acute oral toxicity of the substance in rats of both sexes observed for a period of 15 days is: LD50 (rat): 1163 mg/kg bw (for males: 1118 mg/kg bw and for females: 1293 mg/kg bw).

 

95 % Confidence Limits were: Males/females: 647 — 1757 mg/kg bw, males 165 — 2345 mg/kg bw and females 427 — 2341 mg/kg bw.

The following symptoms were observed:

At 600 mg/kg bw: sedation, dyspnea, hunched posture, ruffled for.

At 2000 mg/kg bw: sedation, dyspnea, ataxia, ventral body position, hunched posture, spasms (males), diarrhea (males), ruffled fur.

At 5000 mg/kg bw: sedation, coma, dyspnea, latero-abdominai position, hunched posture, spasms (males), ruffled for.