Polymer with 2-Butyne-1,4-Diol and (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other: GLP comparable to guideline study, available as unpublished report, adequate for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

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:

(11E)-11,12-dibromo-7-(chloromethyl)-2,6,9,14,18-pentaoxanonadec-11-ene-4,16-diol; (12E)-12,13-dibromo-1,21-dichloro-8-(chloromethyl)-5,17-bis(methoxymethyl)-4,7,10,15,18-pentaoxahenicos-12-ene-2,20-diol; (8E)-8,9-dibromo-13-(hydroxymethyl)-2,6,11,15-tetraoxahexadec-8-en-4-ol; (8E)-8,9-dibromo-2,6,11,15-tetraoxahexadec-8-ene-4,13-diol

EC Number:

617-903-6

Cas Number:

86675-46-9

Molecular formula:

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

IUPAC Name:

(11E)-11,12-dibromo-7-(chloromethyl)-2,6,9,14,18-pentaoxanonadec-11-ene-4,16-diol; (12E)-12,13-dibromo-1,21-dichloro-8-(chloromethyl)-5,17-bis(methoxymethyl)-4,7,10,15,18-pentaoxahenicos-12-ene-2,20-diol; (8E)-8,9-dibromo-13-(hydroxymethyl)-2,6,11,15-tetraoxahexadec-8-en-4-ol; (8E)-8,9-dibromo-2,6,11,15-tetraoxahexadec-8-ene-4,13-diol

Test material form:

liquid: viscous

Details on test material:

- Name of test material (as cited in study report): IXOL M125
- Physical state: treacly liquid
- Lot/batch No.: 1013
- Purity: >99%

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
- Weight at study initiation: 180-200 g at arrival
- Fasting period before study: 16 hours before dosing until 6 hours after dosing
- Housing: continuously in stainless steel wire cages with 5 animals per cage
- Diet: a standard laboratory diet RMH-TM, Hope Farms, Woerden, The Netherlands
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 40-50
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1% tragacanth

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg

Doses:

250, 500, 1000 and 2000 mg/kg bw

No. of animals per sex per dose:

5 males/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed the first half an hour and at 1.5, 3, 6, 24 and 48 hours after dosing and thereafter on each day till the end of the experiment. The rats were weighed one day before and at 2, 7 and 14 days after dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

LD50 and 95% CI were calculated according to the method of Weil.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

917 mg/kg bw

Based on:

test mat.

95% CL:

>= 490 - <= 1 715

Mortality:

4 rats died in the 2000 mg/kg bw group; 3 animals died in the 1000 mg/kg bw group and 1 animal died in 500 mg/kg bw group.

Clinical signs:

other: The signs were mainly indicative of effects on the autonomic nervous system (ptosis, diminished respiratory rate, respiratory difficulties, piloerection and hypothermia), on the central nervous system (apathy and positional passivity), on motor coordinati

Gross pathology:

Autopsy of rats that died as a result of treatment, revealed effects on the gastro-intestinal tract (irritation), kidneys (pale), liver (pale), lungs (red spots) and thymus (red spots). In the surviving animals no abnormalities were detected.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 = 917 (490-1715) mg/kg bw in male rats.

Executive summary:

In a GLP compliant acute oral toxicity study, performed according to a protocol similar to the OECD guideline 401, male Wistar rats (5/dose) were exposed to 250, 500, 1000, and 2000 mg/kg bw of Polyol IXOL M125. At 250 mg/kg bw no mortalities were observed; at 500 mg/kg bw, 1 animal died; at 1000 mg/kg bw: 3 animals died and 2000 mg/kg bw: 4 animals died. In survivors, in the first days after dosing there was a weight loss in all dose groups, except the 250 mg/kg bw group. Thereafter there was a recovery. Clinical signs were mainly indicative of effects on the autonomic nervous system (ptosis, diminished respiratory rate, respiratory difficulties, piloerection and hypothermia), on the central nervous system (apathy and positional passivity), on motor coordination (abnormal gait, abnormal body posture, diminished locomotor activity, loss of righting-reflex) and on muscle tone (decreased abdominal and limb tone and paralysis). Autopsy of rats that died as a result of treatment, revealed effects on the gastro-intestinal tract (irritation), kidneys (pale), liver (pale), lungs (red spots) and thymus (red spots). In the surviving animals no abnormalities were detected. The LD50 was determined to be 917 mg/kg bw.