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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
Study period:
May - July 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
not specified
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2'-iminobis[4,6-diamino-1,3,5-triazine]
EC Number:
222-695-1
EC Name:
2,2'-iminobis[4,6-diamino-1,3,5-triazine]
Cas Number:
3576-88-3
Molecular formula:
C6H9N11
IUPAC Name:
2-N-(diamino-1,3,5-triazin-2-yl)-1,3,5-triazine-2,4,6-triamine
Constituent 2
Reference substance name:
melam
IUPAC Name:
melam
Details on test material:
Name of test material (as cited in study report): Melam
Chemical name: 2,2'-iminobis[4,6-diamino-1,3,5-triazine]
Lot No.: ACES062008
CAS No.: 3576-88-3
Appearance: Crystalline powder
Molecular formula and weight: C6H9N11, 235.21
Purity: 98.45%
pH: 9.6
Density: 1679 kg/m3 (at 20 °C)
Melting point: > 300 °C
Particle size: 0.138-30.200 µm
Manufacture date: Feb. 17,2009
Expiry date: Feb. 16,2010
Storage condition: Room temperature (21.7-24.9°C)
Handling and notice: Routine hygienic procedures will be used to ensure the health and safety of the personnel according to MSDS.
Receipt date: May 18, 2009
Residue treatment: Disuse after completion of the study

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: ORIENTBIO INC., Korea
- Age at study initiation: 8 weeks
- Weight at study initiation: 174.0-203.3 g
- Fasting period before study: approximately 16 hours, drinking water was not withheld
- Housing: Stainless steel wire cages, 260Wx350Dx21OH (mm); 1 animal
- Diet: Pelleted food for laboratory animal, provided ad libitum; Harlan Laboratories, Inc., U.S.A .
- Water: Public tap water in Cheongju-si was filtered and irradiated by ultraviolet rays.
Purified drinking water was provided ad libitum using a polycarbonate bottle (500 mL) in a quarantine room and an automatic watering system in an animal room. Samples of drinking water are analyzed for specified microorganism once a month and all environmental contaminants once
a year. The results were confirmed to meet the allowable standard of this facility.
- Acclimation period: 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1-23.7
- Humidity (%): 36.9-58.5
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): Cycle of 12 hours light and 12 hours dark (light on: 7 a.m., light off: 7 p.m.)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Water for injection
Details on oral exposure:
VEHICLE
- Lot no.: GBA9001

DOSE VOLUME APPLIED: 10 mL/kg b.w.
Doses:
Dose level: 2000 mg/kg bw for steps 1 and 2.
Rationale for the selection of the starting dose: The starting dose level for this study was selected as the dose of 2000 mg/kg because the
LD50 value of test substance for rats is greater than 4000 mg/kg, according to the MSDS.
No. of animals per sex per dose:
3 females in step 1 and another 3 females on step 2.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: prior to dosing (Day 0), on Days 1,3, 7, and the day of necropsy (Day 14).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Other than mean value calculations from the data obtained through this study, statistical analysis was not performed.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
During the observation period, there were no deaths for any animals treated with 2000 mg/kg.
See Attachment Table 1
Clinical signs:
In 3 animals treated with 2000 mg/kg revealed compound-colored stool on Day 1 after
administration, and then returned to a normal appearance on Day 2 after administration.
It was considered to be test substance-related temporary changes.
See Attachment Table 2
Body weight:
Normal body weight gain was seen in all animals treated with 2000 mg/kg.
See Attachment Figures 1 and 2, Table 3.
Gross pathology:
At necropsy, no macroscopic findings were noted in all animals treated with 2000 mg/kg.
See Attachment Table 4

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
There were no deaths for any animal treated with 2000 mg/kg. No test substance-related effects were noted in clinical signs, body weights and necropsy in all animals treated with 2000 mg/kg.
Based on the results of acute oral toxicity study in rats, GHS classification of the test substance, Melam, was classified to be Category 5.
Executive summary:

This study was to assess the toxicity and GHS classification of the test substance, Melam, following a single oral administration to 8 weeks old female Sprague-Dawley rats. Test groups consisted of two groups at 2000 mg/kg of Steps 1 and 2, each step having three animals. All animals were monitored for clinical signs and body weight changes during the 14 days of observation period after administration. They were subjected to

gross necropsy at the end of the observation period.

There were no deaths for any animals treated with 2000 mg/kg. No test substance-related effects were noted in clinical signs, body weights and necropsy in all animals treated with 2000 mg/kg.

Based on the results of acute oral toxicity study in rats, GHS classification of the test substance, Melam, was classified to be Category 5.