Melamine

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

repeated dose toxicity: inhalation

Remarks:

other: study, with some elements of a subchronic toxicity test

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

Insufficient description of the study. It is not even clear, if a vapour, a dust or an aerosol was applied.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1993

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A 4-months study with some elements of a toxicity and a reproduction toxicity study was performed.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Melamine

EC Number:

203-615-4

EC Name:

Melamine

Cas Number:

108-78-1

Molecular formula:

C3H6N6

IUPAC Name:

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

Test animals

Species:

rat

Strain:

other: hybrid albino

Sex:

male

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

other: no data

Details on inhalation exposure:

No data.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The amount of melamine in the air prevailing in the treatment cages was determined by thin-layer chromatography, using the method developed by V.V. Tarasov et al. The detection limit for melamine in this method was 2 μg in the volume of sample to be analyzed, and it was 0.007 mg/m3 in the air when 300 liters of air were taken for a sample.

Duration of treatment / exposure:

17 weeks

Frequency of treatment:

24 h, continuously.

Doses / concentrations

Remarks:

Doses / Concentrations: 0.50 - 0.058 - 0.011 - 0.00 mg/m3
Basis: nominal conc.

No. of animals per sex per dose:

36 males

Control animals:

yes

Details on study design:

Post-exposure period: no data

Examinations

Observations and examinations performed and frequency:

To study the general toxicity of melamine, the behavior of the animals, the weight, and the following parameters were determined:
- aggregate threshold value (ATV),
- level of the sulfhydryl (thiol) group in the blood,
- cholinesterase activity in whole blood,
- blood level of lactic acid and glutaric (pyrotartaric) acid,
- activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST),
- serum lysozyme level, and
- the total and fractional protein values in the serum.

Sacrifice and pathology:

After the four-month exposure period, the internal organs of the animals were subjected to pathological and histochemical examination.

Statistics:

Data obtained were processed statistically with the aid of Student’s t test.

Results and discussion

Results of examinations

Details on results:

The experimental animals in the dosed groups were active during the chronic toxicity test and showed a moderate weight increase. They did not exhibit any noticeable difference in behavior from the controls.

ATV was decreased in the mid and high dosed group.
Cholinesterase: cyclic variations in the mid and high dosed group.
Fractional protein values: changes in the mid and high dosed group.
ALT and AST: changes in the mid and high dosed group.
Glutaric (pyrotartaric) acid: changes in the mid and high dosed group.
Sulfhydryl (thiol) group in the blood: changes in the mid and high dosed group.

The pathological and histochemical investigations indicated some changes in the high and mid dose group, characterized by a basic hematopoietic disorder and by dystrophic alterations in the internal organs (brain, lungs, liver, spleen and testicles). However, no pathological changes were observed in the low dose group.

Effect levels

Dose descriptor:

NOAEC

Effect level:

0.01 mg/m³ air

Sex:

male

Basis for effect level:

other: Various toxic effects.

Target system / organ toxicity

Critical effects observed:

yes

Lowest effective dose / conc.:

0.058 mg/m³ air

System:

other: A basic hematopoietic disorder and dystrophic alterations in the internal organs (brain, lungs, liver, spleen and testicles)

Treatment related:

yes

Dose response relationship:

no

Relevant for humans:

no

Applicant's summary and conclusion

Conclusions:

The study is not considered to be reliable.

Executive summary:

A 4-months toxicity study with some elements of a reproduction toxicity study was performed with rats.

A melamine concentration of 0.058 mg/m3 was found to be the threshold value. In a concentration of 0.01 mg/m3, melamine did not cause any general toxic or gonadotoxic symptoms and is therefore now classed as inactive at this concentration.

This is an unreliable study.