Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Repeated-dose exposure to melamine cyanurate revealed kidney as the target organ of systemic toxicity at very low doses. The mode of action is precipitation of poorly soluble crystals of the parent compound which is not related to reproductive toxicity.

Experimental data on the components melamine and cyanuric acid show no reproductive toxicity hazard at doses exceeding by far the threshold for melamine cyanurate crystal formation in the kidney. Therefore, both components were tested for fertility or toxicity to reproductive organs at much higher doses that could be tolerated for melamine cyanurate.


Short description of key information:
No adverse effects were observed in a GLP compliant screening study according to OECD testing guideline 422 with cyanuric acid (MHLW 1997). No effects were reported in a short summary of a three-generation study with sodium cynurate applied via drinking water up to the highest dose of 5375 mg/L (Wheeler 1985). No indication of toxicity to reproductive organs were observed in the long-term studies with melamine (US NTP). For melamine cyanurate, a study following the procedure of OECD 421 (feed application) is in the in-life phase (August 2016).

Effects on developmental toxicity

Description of key information
 For melamine, no developmental toxicity was observed in a GLP compliant study following OECD testing guideline 414 (BASF 1996). Absence of a teratogenic potential was reported in a short summary of a teratogenicity study with sodium cyanurate (Cascieri 1983) and in a screening study according to OECD 422 (MHLW 1997). A study following the procedure of OECD 421 (feed application) is in the in-life phase (August 2016).    
    
    
    

the in-life phase (Augu

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

The potential for developmental toxicity is derived from experimental data on the components melamine and isocyanuraric acid. Melamine cyanurate is of much more effective in causing nephrotoxicity than either melamine or cyanuric acid by themselves. Therefore, the experimental data on the components is suitable for assessment of a reproductive toxicity hazard. For melamine, no developmental toxicity was observed in a GLP compliant study following OECD testing guideline 414 (BASF 1996); the NOAEL of maternal toxicity was 400 mg/kg bw. Absence of a teratogenic potential at 5000 mg/kg bw was reported in a short summary of a teratogenicity study with sodium cyanurate (Cascieri 1983). No developmental toxicity hazard was identified in a GLP compliant screening study (OECD 422) with cyanuric acid up to the highest tested dose of 600 mg/kg bw (MHLW 1997). The doses tested for the components exceed by far the effective doses causing renal toxicity, therefore it is concluded that melamine cyanurate has no teratogenic properties.

This is confirmed by a supporting developmental toxicity study in rats conducted with a 1:1 mixture of melamine and cyanurate (Kim et al., 2013). In this study, developmental effects were confined to reduced fetal body weight and delayed fetal ossification, which were both noted at a dose level associated with clear maternal toxicity. The 1:1 mixture of melamine and cyanurate was not teratogenic under the conditions of this reliable supporting study.

Toxicity to reproduction: other studies

Additional information

No experimental data is available in how far melamine cyanurate is transferred to human breast milk.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for reproductive toxicity under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

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

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for reproductive toxicity under Regulation (EC) No. 1272/2008.