Laboratory animal models

Adult subjects who ingested soil (particle size less than 250 im) from the Bunker Hill NPL site absorbed 26% of the resulting 250 pg/70 kg body weight lead dose when the soil was ingested in the fasted state and 2.5% when the same soil lead dose was ingested with a meal (Maddaloni et al. 1998). There are no reported measurements of the absorption of soil-bome lead in infants or children. Additional evidence for a lower absorption of soil-bome lead compared to dissolved lead is provided from studies in laboratory animal models. In immature swine that received oral doses of soil from one of four NPL sites (75 or 225 ig Pb/kg body weight), bioavailability of soil-bome lead ranged from 50% to 82% of that of a similar... 

Many laboratory animal models have been used to describe the toxicity and pharmacology of chloroform. By far, the most commonly used laboratory animal species are the rat and mouse models. Generally, the pharmacokinetic and toxicokinetic data gathered from rats and mice compare favorably with the limited information available from human studies. PBPK models have been developed using pharmacokinetic and toxicokinetic data for use in risk assessment work for the human. The models are discussed in depth in Section 2.3.5. As mentioned previously, male mice have a sex-related tendency to develop severe renal disease when exposed to chloroform, particularly by the inhalation and oral exposure routes. This effect appears to be species-related as well, since experiments in rabbits and guinea pigs found no sex-related differences in renal toxicity. 

As indicated above and discussed below, the health effects of DEHP are generally well characterized by the oral route in laboratory animal models. While additional information is always desirable, from a health assessment perspective, there appear to be few overriding needs for additional toxicological information for the principal route of human exposure to DEHP. Of particular importance are additional data that could enable derivation of an acute-duration oral MRL, which is currently precluded by insufficient information on male reproductive system development in offspring acutely exposed during gestation and/or lactation. 

Traditionally, drug metabolism studies rely on the use of model systems to predict the intermediates and products of dmg metabolism in humans. For these purposes whole animal systems are in use, especially small laboratory animal models (e.g. rat, dog, cat, guinea pig, rabbit). In vitro studies are generally used to complement and specify the data obtained using perfused organs, tissue or cell cultures, and microsomal preparations. As discussed in more detail later, microorganisms can be used as model systems as well. 

There are a wide range of chlorinated dibenzo-p-di-oxins varying in the extent of their chlorination. Dioxin nomenclature is based on the number and positions of carbon atoms that are chlorinated and include mono-, di-, tetra-, penta-, hexa-, hepta-, and octachlorinated congeners. 2,3,7,8-Tetrachloro-dibenzo-/7-dioxin (2,3,7,8-TCDD, more commonly referred to as TCDD or dioxin) is usually of greatest concern because of high toxicity in laboratory animal models, its widespread distribution and persistence in the environment, bioaccumulation potential, and because the greatest amount of data exists for this form. 

Investigation of Cannabinoid Withdrawal in Laboratory Animal Models. . . 700... 

Traditionally, drug metabolism studies have relied on the use of model systems to predict metabolic pathways in human. For this purpose, either in vivo whole animal system (utilizing small laboratory animal models) or in vitro enzyme systems (microsomal preparations, tissue cultures or perfused organ systems) have been widely employed [14, 15]. In biomedical research, animal systems continue to serve an important role as models for biological responses in man. 

Since 2000, the estrogens Ei and E2 have been analyzed in tissues from a variety of laboratory animal models. The estrogens were extracted from the tissues and analyzed by HPLC with multichannel electrochemical detection... 

Since percutaneous permeation studies are frequently conducted using laboratory animal models such as rats, mice, and guinea pigs, it should be understood that wide dilferences exist between these models, including the thickness of the stratum corneum, the number of sweat glands and hair follicles, and the distribution of the papillary blood supply. These factors affect both the routes of transport and the resistance to penetration. In addition, the human skin differs from different animal species in biochemical composition and permeability. The subtle biochemical differences between human and animal skin may alter the reaction between permeant molecules and the skin [37]. 

Retinal cell biology is the key to understanding how the retina works and how certain conditions such as retinopathies or treatments such as laser photocoagulation affect its ability to function. Much of this work is done on a microscopic scale using retinal cells from laboratory animal models or human eyes from autopsies. Scientists look at experimental therapies and their impact on the retina at the cellular level. They can provide high-resolution imaging of how these cellular changes affect visual outcomes. 

Humans are animals, and our shared molecular ancestry establishes the basis for the use of animal models in medical research. Depending upon the system being investigated, the animal models may have to be quite similar to humans (an argument for the use of primates in research that focuses on infectious diseases), or they may not have to be similar at all (as is the case when the giant squid, Loli fo, is used to elucidate neural function). The litde lab mouse may indeed lose its position as the default laboratory animal model, but more likely it will just have to make room for other species to share its valued position. After aU, outside appearances can be deceiving, as it is what s inside biochemically that truly counts. 

While there is some evidence that exposure to NP or OP may have adverse effects on specific organs, including the kidney, heart, and liver, the majority of the studies evaluating toxic effects of APs have focused on male and female reproduction and endocrine effects, immune function, and neurological and behavioral endpoints. This section will briefly highlight some of the studies that have assessed effects of AP exposure on these organs and functional systems, especially those from mammalian laboratory animal models and tissue culture systems. 

Development of a laboratory animal model that gets coronary atherosclerosis lesions comparable to those of the human and in a manner similar to man ... 

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