2-Butyne-1,4-diol, polymer with 2-(chloromethyl)oxirane, brominated, dehydrochlorinated, methoxylated

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 near -guideline study, no restrictions, fully adequate for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar 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:

2-Butyne-1,4-diol, polymer with 2-(chloromethyl)oxirane, brominated, dehydrochlorinated, methoxylated

EC Number:

614-503-3

Cas Number:

68441-62-3

Molecular formula:

(C3H7O2)xC4H4O2Br2(C4H9O2)y with x + y = 2.5

IUPAC Name:

2-Butyne-1,4-diol, polymer with 2-(chloromethyl)oxirane, brominated, dehydrochlorinated, methoxylated

Constituent 2

Reference substance name:

Triethyl phosphate

EC Number:

201-114-5

EC Name:

Triethyl phosphate

Cas Number:

78-40-0

Molecular formula:

C6H15O4P

IUPAC Name:

triethyl phosphate

Test material form:

liquid: viscous

Details on test material:

- Name of test material (as cited in study report): B251, suspensions in 1% tragacanth mucilage.
- Lot/batch No.: Batch No. 1106
- Physical state: liquid
- Analytical purity: not specified

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: TNO, Zeist, the Netherlands
- Age at study initiation: not specified
- Weight at study initiation: 180-200 g at arrival
- Fasting period before study: 16 hours prior to dosing until 6 hours post-dosing
- Housing: five per cage
- Diet: free access
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 60-70
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test material was given by stomach tube. The dose volume was 10 ml/kg.

Doses:

625, 1250, 2500 and 5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Clinical signs:
Rats were observed at about 0, 0.5, 1.5, 3, 6, 24 and 48 hours after dosing and thereafter on each day until the end of the experiment. Any sign of intoxicification during the 14 days observation period was recorded.

Body weight:
The rats were weighted one day before and at 2, 7 and 14 days after dosing.

Autopsy:
Gross post-mortem examination was made on all rats that died during the observation period. At the end of the experiment, the rats were killed by ether inhalation and autopsied. All the groups were examined.

Statistics:

LD50 and 95% confidence limits were calculated according to the method of Weil (1952): Biometrics 8: 249:263.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

1 337 mg/kg bw

Based on:

test mat.

95% CL:

862 - 2 070

Mortality:

625 mg/kg bw: no mortalities;

1250 mg/kg bw: 3/5 died;

2500 mg/kg bw: 4/5 died (two between 6 and 24 hours, and two between 24 and 48 hours after dosing);

5000 mg/kg bw: 5/5 died (one between 1.5 and 3 hours, two between 3 and 6 hours and two between 6 and 24 hours).

Clinical signs:

other: no signs were observed in control and animals treated with 625 mg/kg bw; for 1250 mg/kg bw moderate to severe signs (mostly) with onset between 6 and 24 hours after dosing were as for 2 500 mg/kg bw except that twitches, diminished righting reflex and sa

Gross pathology:

Autopsy of the rats that died as a result of treatment revealed effects on the gastro-intestinal tract (irritation), kidneys (pale), liver (pale), lymph nodes (congested) and lungs (red spots).
One surviving rat of the 2500 mg/kg bw group had a slightly enlarged liver and slight irritation of the fundus. The other surviving rats had no effects.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of Polyol IXOL B251 was 1337 mg/kg bw.

Executive summary:

The acute oral toxicity of Polyol IXOL B251 was investigated in a GLP compliant study using a protocol similar to OECD guideline 401 (Duphar B.V., 1985a). Single doses of B251 in 1%-tragacanth were given by stomach tube to groups of five male fasted rats. The doses were 6 25, 1250, 2500 and 5000 mg/kg bw. The animalswere weighed one day before and at 2, 7 and 14 days after dosing. Any toxic sign occurring during the 14-day observation period was recorded. Gross post-mortem examination was done on dead animals and on the survivorsat the end of the 14-day observation period.

At 625 mg/kg bw, no mortalities were observed; at 1250 mg/kg bw, 3/5 animals died; at 2500 mg/kg bw: 4/5 animals died and 5000 mg/kg bw: 5/5 animals died. The LD50 was 1337 mg/kg bw. There was a dose-related weight loss in the first days after dosing. Thereafter there was a recovery. The signs were mainly indicative of an effect on the autonomic nervous system (hypothermia, ptosis, diminished respiratory rate, pilo-erection, lacrimation), on the central nervous system (apathy, twitches, diminished alertness and startle response, positional passivity, decreased grooming), on motor coordination (loss of righting reflex, diminished locomotor activity, abnormal gait) and on muscle tone (diminished body tone and limb tone). Autopsy of the rats that died as a result of treatment revealed effects on the gastro-intestinal tract (irritation), kidneys (pale), liver (pale), lymph nodes (congested) and lungs (red spots).