Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
other: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Justification for type of information:
Justification for read-across is given in Section 13 of IUCLID.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted Dec 17th, 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
adopted May 30th, 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
adopted Dec 2002
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Landesanstalt für Umwelt, Messungen und Naturschutz Baden-Württemberg
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Didodecyl fumarate
- Physical state: solid, melt/white
- Analytical purity: 93.8 area-% (GC-FID)
- Lot/batch No.: 0008043725
- Stability under test conditions: The stability of the test item under storage conditions over the test period was guaranteed by the sponsor.
- Storage condition of test material: RT

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany.
- Age at study initiation: 10 weeks (nulliparous, non-pregnant females).
- Weight at study initiation: 164 - 178 g.
- Fasting period before study: feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing in Makrolon cage, type III
- Diet: VRF1 (P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 25 °C.
- Humidity: 30 - 70 %.
- Air changes: approx. 10 per hr.
- Photoperiod: 12 hrs dark / 12 hrs light.

IN-LIFE DATES: from: March 04, 2013 to: March 27, 2013

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml.
- Amount of vehicle: 10 ml/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw.

CLASS METHOD
- Rationale for the selection of the starting dose: due to the chemical structure of the test substance acute toxicity was not expected. Thus a dose level of 2000 mg/kg bw was selected as starting dose.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Group 1: 3 females
Group 2: 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
- Necropsy of survivors performed: necropsy with gross-pathology examination on the last day of the observation period after sacrifice by CO2 - inhalation in a chamber with increasing concentrations over time.

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 in both 2000 mg/kg bw test groups throughout the study.
Clinical signs:
In all animals of the first 2000 mg/kg bw test group impaired general state and piloerection were observed at hour 1 and persisted in two animals until hour 4 or 5 after administration. Diarrhea was noted in one animal at hour 0 while cowering position was observed in all animals at hour 1.
Clinical signs in the second 2000 mg/kg bw test group revealed impaired general state and piloerection and were observed in one animal from hour 0 until hour 2 after administration.
In two animals of this test group no clinical signs were observed during clinical examination.
Body weight:
The mean body weight of the test groups increased throughout the study period within the normal range.
Gross pathology:
There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:
other: not classified according to the the CLP Regulation (EC) No. 272/2008
Conclusions:
LD50 (rat, female) > 2000 mg/kg bw
Executive summary:

The acute oral toxicity of the test material in the female Wistar strain rat was assessed in this acute toxic class test coducted according to the OECD Guideline 423, EU Method B.1 tris, EPA OPPTS 870.1100 and Japan MAFF Testing Guideline of 12 Nosan No. 8147. For this reason, three female rats were used in each step and they were given one single oral dose of the substance at 2000 mg/kg b.w. The animals were observed for fourteen days for signs for clinical signs. Body weights were recorded prior to dosing, weekly thereafter and at the end of the test. At the end of the test the survived animals were sacrificed and were subjected to gross pathological examination.

No mortality occured and no macroscopic pathological changes were observed. The animals showed normal bodyweight gain. All animals of the first test group showed general state and piloerection at hour 1 which were persisted in two animals until hour 4 or 5 after administration. Diarrhea was noted in one animal at hour 0 while cowering position was observed in all animals at hour 1. Clinical signs in the second test group revealed impaired general state and piloerection; these signs were observed in one animal from hour 0 until hour 2 after administration. In two animals of this test group no clinical signs were observed during clinical examination.

LD50 > 2000 mg/kg b.w.