Neurodevelopmental toxicity of methylmercury: Laboratory animal data and their contribution to human risk assessment.
Methylmercury (MeHg) is one of the most significant public health hazards. The clinical findings in the victims of the Japanese and Iraqi outbreaks have disclosed the pronounced susceptibility of the developing brain to MeHg poisoning. This notion has triggered worldwide scientific attention toward the long-term consequences of prenatal exposure on child development in communities with chronic low level dietary exposure. MeHg neurodevelopmental effects have been extensively investigated in laboratory animals under well-controlled exposure conditions. This article provides an updated overview of the main neuromorphological and neurobehavioral changes reported in non-human primates and rodents following developmental exposure to MeHg. Different aspects of MeHg's effects on the immature organism are reported, with particular reference to the delayed onset of symptoms and the persistency of central nervous system (CNS) injury/dysfunction. Particular attention is paid to the comparative toxicity assessment across species, and to the degree of concordance/discordance between human and animal data. The contribution of animal studies to define the role of potential effect modifiers and variables on MeHg dose-response relationships is also addressed. The ultimate goal is to discuss the relevance of laboratory animal results, as a complementary tool to human data, with regard to the human risk assessment process.
Castoldi
Anna F
AF
Toxicology Division, University of Pavia, Via Palestro 26, 27100 Pavia, Italy. anna.castoldi@fsm.it
Onishchenko
Natalia
N
Johansson
Carolina
C
Coccini
Teresa
T
Roda
Elisa
E
Vahter
Marie
M
Ceccatelli
Sandra
S
Manzo
Luigi
L
D000818:Animals; D002648:Child; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000506:poisoning; D005260:Female; D006801:Humans; D020262:Mercury Poisoning, Nervous System / Q000453:epidemiology / Q000503:physiopathology*; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000506:poisoning*; D011247:Pregnancy; D018570:Risk Assessment / Q000379:methods; D013045:Species Specificity
D004785:Environmental Pollutants; D008767:Methylmercury Compounds