Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
6 February - 3 June 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
- Lot No. of test material: 07-170-FIL-2/3
- Appearance: White powder
- Expiration date: May 2010
- Purity: 98.4%
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Texas Animal Specialties, Humble, TX
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Approx. 9 weeks old
- Weight at study initiation: 200 - 205 g (Day 1 weight); 186 - 190 g (Day 0 fasted weight)
- Fasting period before study: 16 hours before dosing
- Housing: Suspended, wire bottom, stainless steel cage; 1 animal per cage
- Diet: PMI Feeds Inc. Formulab #5008 available ad libitum
- Water: Municipal water supply available ad libitum from automatic water system
- Acclimation period: Not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 - 12 air changes/ hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: 25 February - 13 March 2008

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 40% w/v suspension

MAXIMUM DOSE VOLUME APPLIED: 12.5 mL/kg dose was administered
Doses:
5000 mg/kg
No. of animals per sex per dose:
3 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations for mortality and clinical/ behavioural signs of toxicity: at least three times on the day of dosing (Day 0) and at least once daily thereafter for 14 days
- Frequency of weighing: Individual body weights were recorded just prior to dosing and on days 7 and 14 or at the time of discovery after death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
There was no mortality during the study.
Clinical signs:
All animals appeared normal for the duration of the study.
Body weight:
All animals exhibited normal weight gain during the post treatment observation period.
Gross pathology:
The gross necropsy conducted at termination of the study revealed no observable abnormalities.
Other findings:
- Actual temperature: 20 - 24°C
- Actual relative humidity: 27 - 90% (Humidity was outside of the protocol range but did not affect the study outcome)

Any other information on results incl. tables

Table 1: Body weights, time of death and gross necropsy (Dose level 5000 mg/kg, 12.5 mL/kg)

Animal No.

Dose amount (mL)

Date of dosing

Body weights (g)

Time of death*

Gross necropsy findings

Day 0

Day 7

Final

201

2.38

26 Feb 08

190

223

243

Day 14

No observable abnormalities

202

2.34

28 Feb 08

187

218

231

Day 14

No observable abnormalities

203

2.32

28 Feb 08

186

220

232

Day 14

No observable abnormalities

* Day of dosing is Day 0; Day 14 is terminal sacrifice

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 of the test substance, Formononetin, is estimated to be greater than 5000 mg/kg.