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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (Acute Toxic Class Method; GLP, QUA)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
other: US FDA Title 21 Code of Federal Regulations Part 58; US EPA (FIFRA), Title 40 Code of Federal Regulations Part 160; US EPA (TSCA), Title 40 Code of Federal Regulations Part 792;
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries, 59 NohSan, Notifications No.3850; Japanese Ministry of International Trade and Industry, Kanpogyo No.39 Environmental Agency, Kikyoku No.85; Japanese Ministry of Health and Welfare, Ordinance No.21
GLP compliance:
yes (incl. certificate)
Remarks:
OECD Principles of Good Laboratory Practice
Test type:
acute toxic class method
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:
- Name of test material (as cited in study report): FR-6120
- Physical state: white powder
- Analytical purity: ca. 99.5%
- Impurities (identity and concentrations): water (0.27%), Melamine (0.19%) and cyanuric acid (0.012%) (weight%)
- Purity test date: 04 May 2000
- Lot/batch No.: 37432-18-3
- Expiration date of the lot/batch: 22 May 2001
- Stability under test conditions: not indicated
- Storage condition of test material: at room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality) from Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 7 weeks old) were selected
- Weight at study initiation: weight variation did not exceed +/- 20% of the sex mean (see Table 1)
- Fasting period before study: food was withheld overnight (for a maximum of 20 hours) prior to dosing until approximately 3-4 hours after administration of the test substance.
- Housing: Group housing of 3 animals per sex per cage in labelled polycarbonate cages containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany).
- Diet (e.g. ad libitum): Free access to standard pelleted laboratory animal diet (from Carfil Quality BVBA, Oud-Turnhout, Belgium).
- Water (e.g. ad libitum): free access to tap-water.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
A controlled environment was maintained in the room with optimal conditions
- Temperature (°C): 21°C
- Humidity (%): 50%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours dark per day

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: water (Milli-U)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: the vehicle was selected based on a pretest performed at the testing facility

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

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 animals. The first group was treated at a dose level of 2000 mg/kg body weight. 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 to be taken into account for determination of the time interval between the dose groups.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 (the male animals were first tested, followed by female animals, in the absence of mortality in male, one day later)
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 weights (days 1; pre-administration, 8 and 15); clinical signs [at periodic intervals on the day of dosing and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy of survivors performed: yes; at the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: clinical signs, body weight
Statistics:
none necessary

Results and discussion

Preliminary study:
not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: No female (0/3) or male (0/3) animal died at this unique dose level
Mortality:
No mortality occurred.
Clinical signs:
No clinical signs were noted.
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 (Table 1).
Gross pathology:
Macroscopic post mortem examination of the females revealed thickening of the glandular mucosa of the stomach. No abnormalities were found in males.
Other findings:
none reported

Any other information on results incl. tables

Table 1: Body weight (all means of 3 animals)

Group / Sex

Mean body weights ± standard deviation (g) at indicated time period

Day 1

Day 8

Day 15

Group 1 / Males

251 ± 9

320 ± 17

362 ± 31

Group 2 / Females

185 ± 6

224 ± 15

239 ± 12

Applicant's summary and conclusion