Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 August 2006 to 15 September 2006 (In Life)
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted under GLP conditions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Temporary deviations from the maximum level of relative humidity occured. Laboratory historical data do not indicate an effect of the deviations. The study integrity was not adversely affected by the deviations.
Qualifier:
according to guideline
Guideline:
other: EC, Council Directive 67/548/EEC, Annex V, B.1 tris (2004) "Acute Oral Toxicity"
Deviations:
yes
Remarks:
Temporary deviations from the maximum level of relative humidity occured. Laboratory historical data do not indicate an effect of the deviations. The study integrity was not adversely affected by the deviations.
Qualifier:
according to guideline
Guideline:
other: EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity-Acute Toxic Class Method"
Deviations:
yes
Remarks:
Temporary deviations from the maximum level of relative humidity occured. Laboratory historical data do not indicate an effect of the deviations. The study integrity was not adversely affected by the deviations.
Qualifier:
according to guideline
Guideline:
other: JMAFF guidelines (2000) including the most recent partial revisions
Deviations:
yes
Remarks:
Temporary deviations from the maximum level of relative humidity occured. Laboratory historical data do not indicate an effect of the deviations. The study integrity was not adversely affected by the deviations.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): MTDID 6675
- Substance type: Clear colourless liquid
- Physical state: Liquid
- Analytical purity: Formulation tested is 30.0% active ingredient in water
- Purity test date: 12/20/2005
- Lot/batch no.: 140499-8/25
- Expiration date of the lot/batch:02 July 2008
- Storage condition of test material: Refrigerated (2-8 degrees C) in the dark

Test animals

Species:
rat
Strain:
other: Wistar CRl:WI (outbred, SPF-Quality)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Approximately 8 weeks old
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean
- Fasting period before study: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance
- Housing: Group housing of 3 animals per cage in labelled Macrolon cages. Sawdust as bedding and paper as cage-enrichment.
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiaten GmbH, Soest Germany) ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: At least 5 days before the start of treatment
ENVIRONMENTAL CONDITIONS
- Temperature (°C):20.5-23.0 degrees C
- Humidity (%): 30-70%
IN-LIFE DATES: From: 29 August 2006 To: 15 September 2006

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
- Formulation of MTDID 6675 is 30% of the active ingredient (test material) in water
Doses:
-6667 mg/kg (5.747 mL/kg) body weight (2000 mg/kg for the active ingredient)
-1000 mg/kg (0.862 mL/kg) body weight (300 mg/kg for the active ingredient)
No. of animals per sex per dose:
3 females at 6667 mg/kg bw (2000 mg/kg bw active ingredient) dose level and 2 groups of 3 females at 1000 mg/kg bw (300 mg/kg active ingredient)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: At 0, 2, and 4 hours after dosing on day 1, and once daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - 2 000 mg/kg bw
Mortality:
3/3 females in the 2000 mg/kg (active ingredient) group were found dead between days 1 and 2 post-dose. No mortality was observed in either of the 300 mg/kg (active ingredient) groups.
Clinical signs:
Hunched posture was noted at both dose levels (300 and 2000 mg/kg active ingredient). Animals in the 2000 mg/kg (active ingredient) group also exhibited uncoordinated movements and piloerection.
Body weight:
Animals surviving to necropsy (300 mg/kg active ingredient treatment group) had normal body weiht gains over the 14 day study period.
Gross pathology:
In each of the females in the 2000 mg/kg (active ingredient) group isolated dark red foci in the gladular mucosa were found in the stomach.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the conditions of the test, the acute oral LD50 of the test article was between 300 and 2000 mg/kg. According to the Global Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations, the test article should be classified as: harmful if swallowed (Category 4) for acute toxicity by the oral route.
Executive summary:

he objective of this study was to evaluate the acute oral toxicity of the test article (Batch No. 140499-8/25) in rats according to the OECD 423 (2001) test guideline. Initially, the test article was administered by oral gavage to 3 female Wistar rats at 2000 mg/kg (active ingredient). In a stepwise procedure, additional groups of females were dosed at 300 mg/kg. Clinical signs were recorded daily for 2 weeks. Body weights were measured on days 1 (pre-dose), 8 and 15 post-dose. Necropsies were performed on day 15 post-dose. Three females in the 2000 mg/kg dose group were found dead between days 1 and 2 post-dose. Hunched posture was noted at both dose levels (300 and 2000 mg/kg). Animals in the 2000 mg/kg treatment group exhibited hunched posture, uncoordinated movements, and piloerection. Animals surviving to necropsy (300 mg/kg treatment group) had a normal body weight gains over the 14-day study period. Macroscopic post mortum examination revealed abnormalities in the stomach among the animals that died during the study. No treatment-related abnormalities were found in the surviving animals at termination. Under the conditions of the test, the acute oral LD50 of the test article was between 300 and 2000 mg/kg. According to the Global Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations, the test article should be classified as: harmful if swallowed (Category 4) for acute toxicity by the oral route.