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Administrative data

Description of key information

An acute oral toxicity study was performed with rats, performed according to OECD/EC test guidelines. In this study an oral LD50 >2000 mg/kg bw was determined. Based on the physico-chemical properties and based on all other data available, performance of acute studies with other expsoure routes were waived.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
(2001)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
(May 2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
(2002)
Deviations:
no
Qualifier:
according to
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
Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
female
Details on test animals 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
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).
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
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:
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

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.

Justification for classification or non-classification

Based on the available data, DBI is not classified for acute toxicity according to Regulation EC (No.) 1272/2008 (CLP).