In an article published on July 24, 2017 in the peer-reviewed journal Toxicology Letters, Ashley Bolden and colleagues from The Endocrine Disruption Exchange (TEDX) and University of Colorado, both U.S., reported on the results of a scoping review performed to identify potential human health impacts of exposure to melamine (CAS 108-78-1), focusing on the effects other than the well-known renal toxicity of this substance (see FPF dossier on melamine).
A scoping review uses a “systematic methodology to map a research area and identify the available evidence in order to pinpoint potential research questions for systematic review.” While this exercise may generate evidence-based research questions for a subsequent systematic review, by itself it does not yet generate answers to these questions, the authors note.
The literature search performed by the authors identified 2,849 articles in PubMed and 9,362 articles in Web of Science. Of these, 43 studies were identified, based on the title and abstract, to be relevant for inclusion in the present scoping review. All 43 studies were published after 2010. In vivo studies were performed in mice (11 studies), rats (17 studies), fish and chickens (two studies each), and humans (one study). In addition, 15 studies reported on in vitro experiments performed in neuronal, prostate, ovarian, and other cell lines.
Three broad endpoint categories that were identified by this scoping review as candidates for a potential systematic review included neurophysiological effects (i.e. neurological and behavioral), as well as reproductive and anthropometric effects.
Neurophysiological studies, especially those that assessed learning and memory effects of melamine (FPF reported), were concluded to constitute “a strong candidate for systematic review,” because similar endpoints were evaluated across several studies, and the mechanistic data appear to be highly relevant to the observed effects in animals. However, although the authors recommended that “a systematic review of learning and memory be conducted to determine if melamine is a hazard to human health,” they also emphasized that “human epidemiological studies on melamine exposure and neurodevelopment (especially learning and memory), as well as more mechanistic studies would be extremely useful for clarifying the [neurophysiological] effects [of melamine] on human health.”
The studies on potential reproductive effects of melamine concerned both female and male reproduction. Of these, some studies showed effects on female fertility, particularly by influencing the oocyte competence, but others did not. More studies (especially human and mechanistic) would be beneficial to resolve the question posed by the mixed evidence, the authors suggested. Endocrine disruption research initiated by several published studies on endocrine activity of melamine could help find a mechanistic explanation for the observed reproductive effects of melamine.
Among the anthropometric studies looking at body weight, body length, and fetal growth following melamine exposure at several life stages, the first parameter was identified as the most suitable endpoint for a systematic review. However, while both animal and human evidence streams are available, any relevant mechanistic data are currently lacking.
Several endpoints identified as “not well-studied with respect to melamine exposure” included “immune, mutagenic/DNA damage, and hematological endpoints.” Furthermore, no endpoints related to “cardiovascular health, respiratory health, and metabolic diseases” have been examined so far in relation to melamine exposure. When deciding which of these less-studied endpoints to pursue further, “it is important to keep in mind that research and resources should be carefully allotted for the maximum protection of human and environmental health,” the authors noted.
Melamine is frequently used in food packaging and food utensils, including tableware, as well as in a variety of other consumer products, but also in agricultural pesticide formulations. Melamine-containing food contact items are made from the polycondensation of melamine and formaldehyde (CAS 50-00-0). Both of these chemicals were shown to migrate out of melamine-ware, with migration rates increasing after microwave heating (FPF reported) and ageing (FPF reported).
Chemical Watch (August 24, 2017). “NGO calls for more research on melamine’s neurology effects.”
Bolden, A., et al. (2017). “Melamine, beyond the kidney: A ubiquitous endocrine disruptor and neurotoxicant?” Toxicology Letters (published July 24, 2017).