Facing the Challenge of Data Transfer from Animal Models to Humans: the Case of Persistent Organohalogens

A well-documented fact for a group of persistent, bioaccumulating organohalogens contaminants, namely polychlorinated biphenyls (PCBs), is that appropriate regulation was delayed, on average, up to 50 years. Some of the delay may be attributed to the fact that the science of toxicology was in its infancy when PCBs were introduced in 1920's. Nevertheless, even following the development of modern toxicology this story repeats itself 45 years later with polybrominated diphenyl ethers (PBDEs) another compound of concern for public health. The question is why? One possible explanation may be the low coherence between experimental studies of toxic effects in animal models and human studies. To explore this further, we reviewed a total of 807 PubMed abstracts and full texts reporting studies of toxic effects of PCB and PBDE in animal models. Our analysis documents that human epidemiological studies of PBDE stand to gain little from animal studies due to the following: 1) the significant delay between the commercialisation of a substance and studies with animal models; 2) experimental exposure levels in animals are several orders of magnitude higher than exposures in the general human population; 3) the limited set of evidence-based endocrine endpoints; 4) the traditional testing sequence (adult animals – neonates – foetuses) postpones investigation of the critical developmental stages; 5) limited number of animal species with human-like toxicokinetics, physiology of development and pregnancy; 6) lack of suitable experimental outcomes for the purpose of epidemiological studies. Our comparison of published PCB and PBDE studies underscore an important shortcoming: history has, unfortunately, repeated itself. Broadening the crosstalk between the various branches of toxicology should therefore accelerate accumulation of data to enable timely and appropriate regulatory action

Grau de exposição a praguicidas organoclorados em moradores de aterro a céu aberto Levels of exposure to organochlorine pesticides in open-air dump dwellers

OBJETIVO: Estimar o grau de exposição interna aos praguicidas organoclorados (POP) dos moradores de um atêrro a céu aberto. MÉTODOS: Estudo observacional, de aferição simultânea e controlado, cujo fator de estudo foi residir em área contaminada por POP e o efeito foi a concentração sanguínea dessas substâncias. A população de estudo foi de 238 pessoas residentes em um aterro a céu aberto (Pilões), no município de Cubatão, SP; e a população de controle ficou dimensionada em 258 pessoas, também residentes no mesmo município (Cota 200). Foram analisados os praguicidas HCB, p-p'DDT, p-p'DDE, p-p'DDD, o-p'DDT, a HCH; b HCH; g HCH; Aldrin; Dieldrin; Endrin; Heptaclor; Heptaclor-epoxi e Mirex. RESULTADOS: Os teores médios sangüíneos de HCB em Pilões foram de 4,66 µg/L, 155 vezes maior que a média na Cota 200 (0,03 µg/L). Em Pilões, os teores médios de DDT total foram de 3,71 µg/L, duas vezes maior do que na Cota 200 (1,85 µg/L) e o HCH total apresentou concentrações sangüíneas seis vezes maiores em Pilões, 0,84 µg/L, contra 0,13 µg/L. CONCLUSÕES: Evidenciou-se associação positiva entre residir em Pilões e apresentar teores sangüíneos de POP, com risco muitas vezes maior quando comparado a localidades sem a presença desses contaminantes.<br>OBJECTIVE: To estimate the degree of internal exposure to organochlorine pesticides (persistent organic pollutants, POP) among inhabitants of an open-air dump. METHODS: This was an observational study with simultaneous measurement and control, in which the criterion for subjects was that they dwelled in an area contaminated by POP and the effect of such contamination was the concentration of such substances into the blood. The study population consisted of 238 people living on an open-air dump in Pilões, in the municipality of Cubatão, SP, Brazil, and the control population was formed by 258 people, also resident in that municipality, in the Cota 200 district. The following pesticides were analysed: hexachlorobenzene (HCB), p-p'DDT, p-p'DDE, p-p'DDD, o-p'DDT, a HCH (hexachlorocyclohexane); b HCH; g HCH; aldrin; dieldrin; endrin; heptachlor; heptachlor-epoxy and mirex. RESULTS: The average blood level of HCB in Pilões was 4.66 µg/l, which was 155 times higher than the average for Cota 200 (0.03 µg/l). In Pilões the average blood concentration of total DDT was 3.71 µg/l, which was twice the level found in Cota 200 (1.85 µg/l). Total HCH presented blood concentrations that were six times greater in Pilões (0.84 µg/l versus 0.13 µg/l). CONCLUSIONS: A positive association was shown between dwelling in Pilões and the presence of POP in the blood, with much higher risks than in localities without the presence of these contaminants