1,3,5-triazine-2,4,6-triamine phosphate

Endpoint summary

Description of key information

Oral: Melamine phosphate is of low acute oral toxicity as determined in a GLP and OECD-guideline compliant study with rats. No indication of toxicity was observed at the limit dose of 2000 mg/kg bw.

Inhalation: There is no study available with melamine phosphate but with melamine. Absence of systemic toxicity upon acute inhalation is derived from a GLP and OECD guideline compliant study with melamine tested with an aerosol of 5.19 g/m³.

Dermal: As the substance is strongly charged and has a log POW of -3, high dermal absorption is not expected.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001 - 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

Molecular formula: C3H6N6H3O4P
Molecular weight: 224
CAS number: 41583-09-9
Description: White solid
Batch: Not indicated
Purity: >98%
Test substance storage: At room temperature in the dark
Stability under storage conditions: Not indicated
Specific Gravity: 1.74
Stability in vehicle: At least 96 h in 1% Aq. Carboxymethyl cellulose

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Rat, Wistar strain Cri:(WI) BR (outbred, SPF-Quality). Recognised by intemational guidelines as the recommended test system (e.g. OECD, EC). Source: Charies River Deutschland, Sulzfeld, Germany.
Young adult animals (approx. 6 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
Identification by earmark
A controlled environment was maintained in the room with optimal conditions considered as being approximately 15 air changes per hour, a temperature of 21±3°C, a relative humidity of 30-70% and 12 hours artificial fluorescent light and 12 hours dark per day. Temporary deviations from the maximum level for relative humidity (with a maximum of 20%) occurred which might have been caused by cleaning procedures in the room. Based on laboratory historical data these deviations were considered not to have affected the study integrity.
Group housing of 3 animals per sex per cage in labelled Macrolon cages (type IV; height 15 cm) containing purified sawdust as bedding material.
Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Free access to diet and water, fasting period 20h

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

Mortality/Viability: Twice daily.
Body weights: 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. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).

Necropsy: 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.

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Remarks on result:

other: No clinical signs, no effects on body weight and no findings upon necropsy.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

none

Clinical signs:

other: none

Gross pathology:

no findings

Other findings:

none

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP study according OECD TG 423

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

For Read-Across Justification please refer to section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 190 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: CAS 108-78-1

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5 190 mg/m³ air

Quality of whole database:

GLP study according OECD TG 403 (Read Across)

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral

In an acute oral toxicity study, melamine phosphate was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. The study was performed under GLP and according to OECD testing guideline 423. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice on day 15. No mortality occurred and no clinical signs of systemic toxicity were noted. The mean body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. The study is adequate in design and reporting to fulfil the criteria as key study (BASF SE 335183, 2002)

 

Inhalation

Melamine phosphate was not tested for acute inhalation toxicity. It is acceptable to derive the systemic toxicity from experimental data of melamine since both melamine and its phosphate salt have a high solubility in water and a log POW of less than 1 and phosphate is an abundant in cells and body fluids. In addition, the higher molecular weight of melamine phosphate compared to melamine gives a safety margin.

The acute inhalation toxicity of Melamine was observed by nose-only exposure of one group of five male and five female rats to a test atmosphere containing the limit concentration of 5.19 +/- 0.45 g test item per m³ for a single 4-hour period. The Mass Median Aerodynamic Diameter was 6.6 µm. After exposure the animals were observed for 2 weeks. Clinical examinations resulted in changes in breathing pattern in all animals during the exposure to the test item and in blepharospasm in two females shortly after the administration. From day 1 onwards until the end of the experiment on day 14 no abnormalities were observed in the animals. Overall body weight gain was considered to be normal and no mortality occurred. On day 14 after the administration all animals were necropsied. Abnormalities at necropsy consisted of lung changes (petechiae, discolouration and white spots) in all animals and thymic changes (unilateral red thymus) in one male. It was concluded that the 4 -hour LC50 value of Melamine was higher than 5.19 g/m³ for both sexes under the present test conditions (DSM N.V. V98.420, 1998).

 

Dermal

According to ECHA guidance, an acute dermal toxicity study is not necessary. Since melamine does not undergo metabolism (Mast 1983), the acute dermal hazard can be derived from oral data unless high dermal absorption is expected. As the substance is strongly charged and has a log POW of -3, high dermal absorption is not expected. In the absence of acute oral toxicity of melamine phosphate, the LD50 for acute dermal toxicity is expected to be above 2000 mg/kg bw.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes. As a result the substance is not considered to be classified for acute oral, dermal or inhalative toxicity under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EU) No. 2020/217.