Essentiality, toxicity, and uncertainty in the risk assessment of manganese.
J Toxicol Environ Health A
; 73(2): 159-65, 2010.
Article
em En
| MEDLINE
| ID: mdl-20077286
ABSTRACT
Risk assessments of manganese by inhalation or oral routes of exposure typically acknowledge the duality of manganese as an essential element at low doses and a toxic metal at high doses. Previously, however, risk assessors were unable to describe manganese pharmacokinetics quantitatively across dose levels and routes of exposure, to account for mass balance, and to incorporate this information into a quantitative risk assessment. In addition, the prior risk assessment of inhaled manganese conducted by the U.S. Environmental Protection Agency (EPA) identified a number of specific factors that contributed to uncertainty in the risk assessment. In response to a petition regarding the use of a fuel additive containing manganese, methylcyclopentadienyl manganese tricarbonyl (MMT), the U.S. EPA developed a test rule under the U.S. Clean Air Act that required, among other things, the generation of pharmacokinetic information. This information was intended not only to aid in the design of health outcome studies, but also to help address uncertainties in the risk assessment of manganese. To date, the work conducted in response to the test rule has yielded substantial pharmacokinetic data. This information will enable the generation of physiologically based pharmacokinetic (PBPK) models capable of making quantitative predictions of tissue manganese concentrations following inhalation and oral exposure, across dose levels, and accounting for factors such as duration of exposure, different species of manganese, and changes of age, gender, and reproductive status. The work accomplished in response to the test rule, in combination with other scientific evidence, will enable future manganese risk assessments to consider tissue dosimetry more comprehensively than was previously possible.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligoelementos
/
Manganês
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
America do norte
Idioma:
En
Revista:
J Toxicol Environ Health A
Assunto da revista:
SAUDE AMBIENTAL
/
TOXICOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos