Animal metabolic rate

Animal nutritionists have developed formulas to guide them in recommending the amount of food to feed animals in captive situations such as in zoos. First, the number of calorics needed to maintain the animal while at rest is determined—this is called the basal metabolic rate (BMR). In general, a reptile s BMR is only 15 percent that of a placental mammal, while a bird s is quite a bit higher than both a reptile s and a mammal s. For all animals, the number of calories they should receive on a maintenance diet is twice that used at the basal metabolic rate. A growing animal should receive three times the number of calories at the BMR, while an animal in the reproductive phase should receive four to six times the BMR. 

Comparative Toxicokinetics. There are no data on the kinetics of diisopropyl methylphosphonate in humans. Studies in animals suggest that metabolism and urinary metabolite profiles are qualitatively similar among species. Additional studies would be useful in understanding the differences in metabolic rates in species and in determining which animal species is the most appropriate model for human exposure. 

Chlordane is readily absorbed by warm-blooded animals via skin, diet, and inhalation, and distributed throughout the body. In general, residues of chlordane and its metabolites are not measurable in tissues 4 to 8 weeks after exposure, although metabolism rates varied significantly between species. Food chain biomagnification is usually low, except in some marine mammals. In most mammals, the metabolite oxychlordane has proven much more toxic and persistent than the parent chemical. 

These in vivo and in vitro human metabolism studies indicate that pyrethroids undergo rapid metabolism and elimination as observed in rats, and qualitative metabolic profiles (e.g., kinds of metabolites) of pyrethroids are assumed to be almost the same between humans and rats, suggesting that a large database of animal metabolism of pyrethroids could provide useful information for the evaluation of behavior of pyrethroids in humans. Nowadays, human pesticide dosing studies for regulatory propose are severely restricted in the US, and thus detailed comparison of in vitro metabolism (e.g., metabolic rate constants of pathways on a step-by-step basis) using human and animal tissues could be an appropriate method to confirm the similarity or differences in metabolism between humans and animals. 

Metabolism - a final factor in need of comparative studies is the metabolism of xenobiotics. One obvious difference between mammalian and fish species is that their bodies usually function at temperatures at least 10°C different. This fact undoubtedly explains some differences in metabolic rate but even when in vitro incubations are run at optimal temperatures there is a 10 - 100 fold higher rate of mammalian vs. fish metabolism (14, 15). In other words, the level of the xenobiotic-metabolizing capacity, especially for oxidative pathways, of the poikilothermic animals is considerably lower than that of the homeothermic species. Elsewhere in this volume Dr. Bend has focused on this aspect of the handling of xenobiotics by fish (16). 

An interesting observation is tiiat tile larger tiie amount of unsaturated fatty acids in the diet of hibernating animals, prior to hibernation, tiie lower tile body temperature falls during hibernation. The lower tiie temperature, tiie lower is the metabolic rate, which is important in survival from a prolonged period of hibernation. It is suggested that this is caused by an increase in fluidity of membranes but the mechanism is not known. 

Interspecies differences (animal-to-human) mouse, a default value of 7 X 3 rat, a default value of 4 X 3 rabbit, a default value of 2.4 X 3 dog, a default value of 1.4 X 3. The first factor for each species is a calculated adjustment factor, allowing for differences in basal metabolic rate (proportional to the 0.75th power of body weight). The second factor of 3 is the assessment factor applied for remaining uncertainties (Section 5.3.3), for which the default value is 3. For local skin and respiratory tract effects, the assessment factor is 3, as adjustment for differences in body size is inappropriate. 

As mentioned in Section 5.3.2.3, extrapolation using allometric scaling based on metabolic rate assumes that the parent compound is the toxic agent and that the detoxification is related to the metabolic rate and thus controls the tissue level. This is relevant for oral exposure only. With regard to inhalation of substances, which act systemically, the lower detoxification (metabolic) rate in larger animals is balanced by a lower uptake (lower respiratory rate) and thus no scaling factor is needed (ECETOC 2003). 

Extrapolation between species should ideally take into account metabolic routes, i.e., the absence or presence of metabolites, as well as the relative rate of formation of the individual metabolites. In PBPK models (Section 4.3.6), both aspects (nonlinearity, formation of active metabolites) are incorporated. This modeling technique uses compartments that correspond to actual tissues or tissue groups of the body. Size, blood flow, air flow, etc. are taken into account, in addition to specific compound-related parameters such as partition coefficients and metabolic rate data. Based on such studies, target-organ concentrations of active metabolites can be predicted in experimental animals and humans, thus providing the best possible basis for extrapolation (Feron et al. 1990). 

Feron et al. (1990) concluded that the sensitivity of humans to chemicals is probably not very different from that of other mammals, and that a systematic error is made by carrying out extrapolation by using the body weight approach. For metabolizable compounds, the authors strongly recommended a procedure that takes the metabolic rate into account (1F° ) for scaling across species, i.e., dose correction for differences in body size between experimental animals and humans by the caloric requirement approach (Section 5.3.2.3). This approach was also considered to provide a contribution to reducing the size of the traditional safety factor in a justifiable way. 

In order to account for differences in metabolic rates between experimental animals and humans, a surface area to body weight correction (Section 5.3.2.2) is sometimes applied to quantitative estimates of cancer risk derived by low-dose extrapolation. The WHO stated that incorporation of this factor increases the risk by approximately one order of magnitude, depending on the species upon which the estimate is based, and increases the risk estimated on the basis of studies in mice relative to that in rats. The WHO considered incorporation of this factor to be overly conservative, particularly in view of the fact that linear extrapolation more likely overestimates risk at low doses. Therefore, the guideline values for carcinogens were developed on the basis of quantitative estimates of risk that were not corrected for the ratio of surface area to body weight. 

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