1,4-dioxane-2,5-dione

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-06-23 to 1998-07-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

(adopted March 22, 1996)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(September 1996)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,4-dioxane-2,5-dione

EC Number:

207-954-9

EC Name:

1,4-dioxane-2,5-dione

Cas Number:

502-97-6

Molecular formula:

C4H4O4

IUPAC Name:

1,4-dioxane-2,5-dione

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 135-143 g (females), 163-181g (males)
- Housing: a maximum of five animals per cage (stainless steel cages, fitted with wire-screen floor and front)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 or 9 days
- Fasting period before study: overnight

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 54-87.5 (upper limit higher than 70%, because of meteorological circumstances and/or wet cleaning of the animal room)
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 /12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were made within 1 h and within 4h after dosing, and subsequently at least once daily throughout the observation period of 14 days. Body weight was recorded on day 0, and of the surviving animals on days 3, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, gross pathology

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One animal of each sex died before the end of the study period. Male no. 4 was found dead on day 4 after dosing,prior to dead the animal had shown sluggishness, blepharospasm, ataxia, encrustation eyes, piloerection, pallor, coldness and coma. Female no. 13 was found dead on day 1 after dosing, before death occurred this animal had shown sluggishness and ataxia.

Clinical signs:

other: The following signs were observed in the remaining surviving animals: Sluggishness occurred in male nos. 2 and 4 and in female no. 17 at 4 h after dosing and in female no.15 at 4 h and on days 3-5 after dosing. Hunching was observed in female no.15 on day

Gross pathology:

Examination at autopsy of the males and females did not reveal treatment-related gross alterations. The female found dead showed a fluid-filled stomach and intestines, while the male found dead showed a full bladder and clearly visible blood vessels, especially of the abdomen.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

1,4-Dioxane-2,5-dione (glycolide) was examined for acute oral toxicity in an experiment according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) with 3 male and 3 female rats (limit testing with 2000 mg/kg bw). One male and one female died during the 14-day observation period. Thus, the LD50 of 1,4-dioxane-2,5-dione (Glycolide) in male and female rats is considered to exceed 2000 mg/kg bw. However, clinical signs of toxicity other than diarrhoea, piloerection or an ungroomed appearance were observed in the remaining animals, thus, the test item is classified as " may be harmful if swallowed" (Category 5) according to GHS criteria.