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EC number: 203-615-4 | CAS number: 108-78-1
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Epidemiological data
Administrative data
- Endpoint:
- epidemiological data
- Type of information:
- other: Review, with the ultimate aim to determine the threshold of melamine intake at which a urolithiasis risk can be expected.
- Adequacy of study:
- key study
- Study period:
- <=2019
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Review of existing publications.
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- publication
- Title:
- Urolithiasis in children and exposure to melamine: A review of the epidemiological literature
- Author:
- Swaen GMH
- Year:
- 2 019
- Bibliographic source:
- Toxicology Research and Application. Volume 3: 1–10. 2019
Materials and methods
- Study type:
- other: Review of epidemiological publications
- Endpoint addressed:
- other: Urolithiasis
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- A literature search on epidemiology studies with connection to melamine exposure was conducted and the obtained results were assessed. The ultimate aim was to determine the threshold of melamine intake at which a urolithiasis risk can be expected.
- GLP compliance:
- no
Test material
- 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 material form:
- solid: particulate/powder
Constituent 1
Method
- Type of population:
- general
- Ethical approval:
- not applicable
- Details on study design:
- A literature search on epidemiology studies with connection to melamine exposure was conducted and the obtained results were assessed.
To find relevant epidemiology studies on melamine exposure and human health, several literature searches were made in PubMed up to August 2018, with combinations of “melamine” AND “exposure” and “melamine” AND “urolithiasis” and melamine AND “kidney.”
Results and discussion
- Results:
- In total, 667 journal articles were found and the abstracts were reviewed to determine whether the journal article was an epidemiology study. Reference lists of journal articles on epidemiology studies were further searched for relevant publications. In total, 36 epidemiology studies on ME intake and urolithiasis were identified; 26 studies were conducted in Mainland China, 6 in Hong Kong, and 4 in Taiwan; 5 studies were prospective cohort studies of ME-exposed children, 3 were case–control studies, 14 were cross-sectional studies, 8 were prospective follow-up studies on pediatric urolithiasis cases (prognostic studies), and 6 were case series. Three of the 36 were on adults.
In newborns and children under the age of 2, urolithiasis is rarely diagnosed. Urolithiasis prevalence rates between 0.03% and 0.6% have been reported in Hong Kong and of 0.8% in Turkey with its hot and arid climate. In a screening survey in children living in Mainland China, the prevalence of urolithiasis was reported to be 0.41% in non-ME-exposed children and 2.51% in children with intake of ME-tainted formula.
Several epidemiologic studies provided data on the dose–response relationship between daily ME intake and urolithiasis prevalence or data relevant to it. Some of these, including Li, applied flawed methodologies. However, some epidemiologic studies provide several anchoring points for the dose–response relationship between daily ME intake and urolithiasis:
1. The urolithiasis incident was restricted to Mainland China, but there was concern that it had spilled over to Hong Kong,which triggered several investigations there. These Hong Kong studies (Lam HS et al. 2013; Lau YL et al. 2013) found no urolithiasis and concluded the prevailing ME intake had not caused any health effects. Daily ME intake in Hong Kong was reported to be between 0.01 mg/kg/day and 0.21 mg/kg/day. This range therefore must be considered as being an exposure level below the No Observed Adverse Effect Level (NOAEL), how far it is below the NOAEL cannot be determined from these data.
2. The only epidemiology study (Li G et al. 2010) conducted in Mainland China for which the data were analyzed in a dose–response format is unreliable and has serious methodological shortcomings and should not be used for standard setting or for the derivation of dose–response descriptors.
3. Sun et al. 2010 compared ME intake between 79 urolithiasis cases and 103 non-urolithiasis cases. Mean estimated daily ME intake in the cases was 5.17 mg/kg/day as compared to 2.38 mg/kg/day in the controls with a standard deviation of 3.39 mg/ kg/day, suggesting that the latter dose is not associated with urolithiasis risk.
4. In Taiwan, Wang et al. 2009 conducted a case–control study of urolithiasis and estimated ME intake. They reported no increase in urolithiasis in the group, with estimated daily intake of food products containing ME between 0.05 ppm and 2.5 ppm.
Applicant's summary and conclusion
- Conclusions:
- There are no other publications or reports in the open scientific literature that melamine intake can induce urolithiasis in humans other than those from the food tampering incident in Mainland China and the spillover to Taiwan.
All observations described demonstrate that at low melamine intake, the incidence of urolithiasis is not above the background incidence as reported in nonexposed populations. In the epidemiology studies on children with melamine intake and urolithiasis, there is no reliable indication that there is a urolithiasis risk below or in the range of 2.38 mg/kg/day and a standard deviation of 3.39 mg/kg/day.
None of the epidemiologic studies with sound methodology provide evidence that at or below this level a risk of increased urolithiasis exists and consequently they provide no evidence that the WHOestimated TDI of 0.2 mg/kg bw/d is unsafe. - Executive summary:
A literature search on epidemiology studies with connection to melamine exposure was conducted and the obtained results were assessed.
There are no other publications or reports in the open scientific literature that melamine intake can induce urolithiasis in humans other than those from the food tampering incident in Mainland China and the spillover to Taiwan. There is no evidence that melamine intake other than this incident has led to urolithiasis in humans.
All observations described demonstrate that at low melamine intake, the incidence of urolithiasis is not above the background incidence as reported in nonexposed populations. In the epidemiology studies on children with melamine intake and urolithiasis included in this review, there is no reliable indication that there is a urolithiasis risk below or in the range of 2.38 mg/kg/day and a standard deviation of 3.39 mg/kg/day.
The highest daily melamine intake with no increase in urolithiasis reported in the reliable studies has been reported by Sun et al. 2010 which was 2.38 mg/kg/day in the controls free of urolithiasis, with a standard deviation of 3.39 mg/kg/day. None of the epidemiologic studies with sound methodology provide evidence that at or below this level a risk of increased urolithiasis exists and consequently they provide no evidence that the WHOestimated TDI of 0.2 mg/kg bw/d is unsafe.
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