Interspecies variation

We have developed a quantitative structure-activity model for the variations in potency among the nitrosamines and, more recently, a related model for the variation in target organ for a smaller set of nitrosamines. We are currently developing a model for interspecies variation in susceptibility toward carcinogenic nitrosamines. The model for organ selectivity requires terms for the parent nitrosamine as well as for the hypothesized metabolites while the model for potency variations contains terms only for the unmetabolized parent compound. 

Interspecies Variations in Susceptibility. An Important assumption in the development of both the structure-potency model (eq, 1) and the structure-target-organ model (eq, 2) was that all of the test compounds were administered at equal daily... 

It does suggest, however, that our original assumptions concerning d were at least reasonable. In addition, the dose-depen-dent model can be manipulated to examine - in a general sense -some aspects of interspecies variations in susceptibility to nitrosamine carcinogenesis. 

Data for PCP and terrestrial wildlife are incomplete and — in view of the large interspecies variations in sensitivity — need to be collected. Research is needed on reproductive effects in animals following inhalation exposure to PCP additional acute and intermediate toxicity testing chronic duration exposure studies on cancer induction, genotoxicity, and immunotoxicity and the development of alternate biomarkers of PCP exposure and antidotes (WHO 1987 USPHS 1994). Until the results of these studies become available, it seems reasonable to apply to wildlife the same levels recommended for human health protection. 

In the case of marine species, the literature is limited with molluscs and algae being the most frequently employed species (Fig. 7.1.2). The number of references for individual homologues and commercial LAS in the scientific literature is similar, and the range of the interspecies variation is also similar to intra variations. 

Figure 6.3 Simple schematic to illustrate the hierarchy of complexity of systems used for preclinical absorption and disposition investigations of inhaled drug products. Interspecies variation should be considered. In silico modelling based on human data and use of the human perfused lungs can provide complex information regarding human absorption and disposition data.

N. R. Kitteringham, C. Davis, N. Howard, M. Pirmohamed, B. K. Park, Interindividual and Interspecies Variation in Hepatic Microsomal Epoxide Hydrolase Activity Studies with cw-Stilbene Oxide, Carbamazepide 10,11-Epoxide and Naphthalene , J. Pharmacol. Exp. Ther. 1996, 278, 1018 - 1027. 

Uncertainty arising, among other factors, from the variability in the experimental data and intra- and interspecies variation... 

UFi accounts for the interspecies variation in susceptibility. The default value is 10 when correction for differences in body size between humans and experimental animals is based on the body weight. 

In addition to the toxicokinetic and toxicodynamic differences mentioned above, other aspects of differences between experimental animals and humans include different types of organs and tissues, differences in digestion, and differences in the stmcture of the upper respiratory tract. Furthermore, animal studies are performed in homogenous groups of animals, but the results have to be apphed for the protection of all individuals in a heterogeneous population of humans. In consequence of this, interspecies variation must also be expected. 

Assessment Factor eor Interspecies Variation (Animal-to-Human) ... 

The authors noted that it may be expected that the NOAELs from subacute/subchronic smdies tend to be larger than NOAELs from chronic studies and it was considered that the GM ratios for the NOAELs assessed in the studies most likely overestimated the median of the distribution of the extrapolation factor for duration of exposure. The authors also noted that it is very likely that the databases used in these studies overlap each other significantly. It was also pointed out that the distributions presented in Table 5.8 were based on rather variable exposure periods for the subchronic NOAELs, included interspecies variation (no matching for species) for... 

Intraspecies and interspecies variation in sensitivity Behavior and natural history Spatial distribution of residues... 

Level of effect fiiat is acceptable Factors affecting exposure Interspecies variation in sensitivity... 

The wide interspecies variation in the composition (Table 1.1) and the chemistry of the constituents of milk, as discussed elsewhere, renders milk species-specific, i.e., designed to meet the requirements of the young of that species. There is also a surprisingly good relationship between milk yield and maternal body weight (Figure 1.1) species bred for commercial milk production, e.g. dairy cow and goat, fall above the line. 

Williams RT. Interspecies variations in the metabolism of xenobiotics. Biochem Soc Trans 1974 2 359. 

Nasal tissue from animals can be mounted in Ussing chambers, permitting experiments similar to those performed in cell cultures to be performed in intact tissues. The nasal tissues of rabbits, dog, sheep, and cattle have been used and such experiments provide the reassurance that the ex vivo system is representative of the nasal mucosa in vivo. The limitations of this technique are the requirement for the use of fresh tissue, the limited duration of tissue viability, and interspecies variation in tissue permeability and metabolic capacity. 

Grison L., Edwards A. A. and Hossaert-McKey M. (1999) Interspecies variation in floral fragrances emitted by tropical Ficus species. Phytochemistry 52, 1293-1299. 

Regarding biological factors, chemical metabolism is dependent on a wide range of genetic and environmental factors that may be considered as sources of intraindividual, interindividual, and interspecies variation. Intraindividual factors include diet, coexposure to xenobiotics or drugs, health status, or disease. Interindividual factors include age, sex, and genetic makeup, including race. 

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