Dibutyl itaconate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22JAN2016 - 09FEB2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

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:

(2001)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(May 2008)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

(2002)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dibutyl itaconate

EC Number:

218-451-9

EC Name:

Dibutyl itaconate

Cas Number:

2155-60-4

Molecular formula:

C13H22O4

IUPAC Name:

1,4-dibutyl 2-methylidenebutanedioate

Test material form:

liquid

Details on test material:

- Appearance: colourless liquid
- Storage conditions: at room temperature

Test animals

Species:

rat

Strain:

other: Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 8-9 weeks old).
- Weight at study initiation: 139-160g.
- Fasting period before study: yes, overnight.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), except overnight prior to dosing and until 3-4 hours after administration of the test item.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS 9set conditions)
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): at least 10.
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 22JAN2016 to 09FEB2016

Administration / exposure

Route of administration:

oral: gavage

Details on oral exposure:

GAVAGE METHOD: plastic feeding tubes.The test item was stirred on a magnetic stirrer during dosing.

Frequency: single dosage, on day 1.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (2.03 mL/kg) body weight. Dose volume calculated as dose level (g/kg) / specific gravity.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 (2 groups of 3 females in a stepwise manner)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations:
Weighing: Days 1 (pre-administration), 8 and 15.
Mortality/Viability: Twice daily
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.

Statistics:

No statistical analysis was performed (the method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture, piloerection and/or ptosis were noted for all animals on day 1. Alopecia, noted for two animals, is commonly seen in group housed rats and therefore no toxicological significance was attached to this finding.

Body weight:

other body weight observations

Remarks:

The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined.

Executive summary:

An acute oral toxicity study was performed with rats, performed according to OECD/EC test guidelines. Dibuthyl itaconate was dosed at 2000 mg/kg bw/day in a stepwise manner to two groups of three females. Hunched posture, piloerection and/or ptosis were noted for all animals on day 1. No mortality occurred during 14 days observation period. No effects on body weight gain and no abnormalities were found at macroscopic post mortem examination of the animals. Based on these results the LD50 was found to exceed 2000 mg/kg bw.