1,4-dioxacyclohexadecane-5,16-dione

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Range finding test yielded four doses: 3.18; 3.96; 5.0; 6.3 ml/kg;
Appraisal of the safety of foods, drugs and cosmetics (FDA) rules applied

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

1

Reference substance name:

1,4-dioxacyclohexadecane-5,16-dione

EC Number:

259-423-6

EC Name:

1,4-dioxacyclohexadecane-5,16-dione

Cas Number:

54982-83-1

Molecular formula:

C14H24O4

IUPAC Name:

1,4-dioxacyclohexadecane-5,16-dione

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Paderborn
- Weight at study initiation: ca. 140 g
- Fasting period before study: 16 hours before dose administration
- Diet: Standard laboratory diet (Ssniff/Intermast), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 45-55
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

3.18, 3.96, 5.00, and 6.30 ml/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Clinical signs were determined after 20 minutes, 3 hours, 24 hours and 7 days. Body weight was determined on day 0 and 7
- Necropsy of survivors performed: yes

Statistics:

LD50 was determined following Litchfield and Wilcoxon with Gaussian approximation.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4.21 other: mL/kg bw (4500 mg/kg bw)

Based on:

test mat.

Mortality:

3.18 ml/kg: 0/10
3.96 ml/kg: 4/10
5.00 ml/kg: 9/10
6.30 ml/kg: 10/10
Animals that died, died within 24 hours after test substance administration

Clinical signs:

In the doses applied the substance did not show any toxic symptoms other than apathy of the animals after 20 minutes

Body weight:

Average body weights
3.18 ml/kg: 132.5g at day 0 and 150.5g at day 7
3.96 ml/kg: 136.0g at day 0 and 156.5g at day 7
5.00 ml/kg: 135.0g at day 0 and 162.0g at day 7
6.30 ml/kg: 135.0g at day 0

Gross pathology:

No abnormalities were found after necropsy.

Applicant's summary and conclusion

Interpretation of results:

other: not acute harmful

Remarks:

according to EU CLP (EC 1272/2008 and its amendments)

Conclusions:

The LD50 is 4500 mg/kg bw based on a similar to OECD TG 401 study.
GHS: For GHS this substance need to be classified as Acute Tox 5 (H303)

Executive summary:

In an acute oral toxicity study conducted using a protocol similar to OECD guideline 401 (non-GLP), undiluted test substance was administered via oral gavage to fasted Wistar rats (five males + five females/dose) at dose levels of 3.18, 3.96, 5.00 and 6.30 mL/kg. The animals were sluggish soon after administration. In the higher dose groups mortality was observed within 24 hours of dosing, while no additional mortality was observed after 7 days. Necropsy did not reveal any pathological effects. The LD50 was 4.21±1 mL/kg bw (4500 mg/kg bw) both for the 24 hour and 7 day observation period.