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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05 November -21 November 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: the study has been performed according to EC and OECD guidelines and according to GLP principles

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-[2-(carboxymethyl)phenoxy]-3,4-dimethylbenzoic acid
EC Number:
601-485-7
Cas Number:
117570-93-1
Molecular formula:
C17 H16 O5
IUPAC Name:
2-[2-(carboxymethyl)phenoxy]-3,4-dimethylbenzoic acid
Constituent 2
Reference substance name:
2-(6-carboxy-2,3-dimethylphenoxy)-benzeneacetic acid
IUPAC Name:
2-(6-carboxy-2,3-dimethylphenoxy)-benzeneacetic acid
Details on test material:
- Name of test material (as cited in study report): ASA404 C7
- Substance type: off-white powder
- Physical state: solid
- Analytical purity:99.9%
- Purity test date: 18 September 2008
- Lot/batch No.: 072301
- Expiration date of the lot/batch:18 March 2009
- Stability under test conditions: not indicated
- Storage condition of test material: stable

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain; Wistar strain Crl:WI (Han)
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 9 weeks
- Weight at study initiation: 149-176 g
- Fasting period before study: overnight (for a maximum of 20 hours) until 3-4 hours after administration of test substance
- Housing:Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material and paper as cage-enrichment
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period:at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 - 21.4°C
- Humidity (%): 37 - 62%
- Air changes (per hr):approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 05 November 2008 To: 21 November 2008

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: The vehicle was selected based on trail formulations performed at NOTOX and on test substance data supplied by the sponsor

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw


DOSAGE PREPARATION (if unusual):The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups
Doses:
2000 mg/kg body weight and 2000 mg/kg body weight
No. of animals per sex per dose:
6 females (3 females per dose group)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: twice daily
Body weighhts: Days 1 (pre-administration), 8 and 15.
clinical signs: at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
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
Mortality:
No mortality occurred
Clinical signs:
Hunched posture and piloerection were noted in all animals on Day 1.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of 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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of ASA404 C7 in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Based on these results ASA404 C7 does not have to be classified and has no obligatory labeling requirement for oral toxicity according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007) and EC criteria for classification and labeling requirements for dangerous substances and preparations (Council Directive 67/548/EEC).

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