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

Abstract

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.

Differential gene expression and a functional analysis of PCB-exposed children: Understanding disease and disorder development

“…Chronic exposure is also different from in vitro and in vivo animal studies, as observed by various research groups (Ulbrich and Stahlmann, 2004; Suvorov and Takser, 2008). In chronic environmental exposure, multiple toxicants can act synergistically to induce a more lethal effect (Loeffler and Peterson, 1999).…”

Maternal transfer of BDE-47 to offspring and neurobehavioral development in C57BL/6J mice

“…The reason for opposite effects in the two studies is unclear, but one explanation could be related to stress associated with swimming in the MWM [13]. Suvorov et al [62] found that exposure of rat dams to 0.2 mg/kg BDE-47 every 5 th day from GD 15 to PND 20 decreased levels of circulating corticosterone (CS), caused adrenal atrophy, impaired adrenal zonation, and reduced expression of steroidogenic enzymes in offspring. Decreased levels of CS have been found to improve cognitive performance in a variety of tests (e.g., Morris water maze) as well as decrease reactivity to external stressors [37,38].…”

Metabolomic Analysis in Brain Research: Opportunities and Challenges

“…Post-mortem human tissues are in low availability and vary with respect to patients' characteristics, disease state, therapeutic treatment, cause of death, collection, and handling procedure, differences that can affect the acquired metabolic profiles (Samarasekera et al, 2013 ). On the other hand, animal model studies depend on the model accuracy in simulating human pathophysiology (Suvorov and Takser, 2008 ; McGonigle and Ruggeri, 2014 ). Regarding metabolism in particular, a disorder may cause opposite effects in lab rodents compared to humans (Panzoldo et al, 2011 ; Blekhman et al, 2014 ; Martens, 2015 ).…”