Relevance to humans

The effects of CR on longevity in humans have not been evaluated directly. Kagawa et al. examined a proportion of centenarians in Okinawa Prefecture compared with those in other regions of Japan [78]. Okinawa residents have a 

NIA Primate Aging Study Male Rhesus Monkeys 

Baltimore Longitudinal Study of Aging Male Humans 

Albanes et al. [79] examined the relationships among energy balance, body size and cancer risk using data from the first U.S. National Health and Nutrition Examination Survey and its follow-up study. The age-adjusted relative risk of cancer for men above 169 cm in height is significantly increased by 1.4- to 1.5-fold when compared to that for men under 169 cm 

More controlled studies of a CR-like regimen have been reported for human subjects in Biosphere [81,82]. The caloric intake was reduced between 20% and 30% from 10 weeks to over 2 years. This regimen reduced body weight, adiposity, blood pressure, blood glucose, plasma insulin, and serum lipids. 

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I. K. O Neill, J. Chen, and H. Bartsch, eds.. Relevance to Human Cancer of N-Nitroso Compounds, Tobacco Smoke andMjcotoxins, lARC Scientific Pubhcation No. 105, International Agency for Research on Cancer, Lyon, Prance, 1991. 

Savolainen, K. M. (1997). The use of maximum tolerated dose in rodent carcinogenicity bioas says and its relevance to human risk assessment. Hum. Exp. Toxicol. 16, 190-192. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor approach. They are below levels that might cause adverse health effects in the people most sensitive to such chemical-induced effects. MRLs are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level above the MRL does not mean that adverse health effects will occur. 

Currently, MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end point considered to be of relevance to humans. Serious health effects (such as irreparable... 

Ongoing epinephrine research relevant to human anaphylaxis is critically important. In its absence, the use of epinephrine in anaphylaxis treatment in the 21st century will continue to be based mostly on clinical experience, or worse, on expedience, instead of on clinical science. 

Kishi R, Harabuchi 1, Ikeda T, et al. 1993. Acute effects of trichloroethylene on blood concentrations and performance decrements in rats and their relevance to humans. Br J Ind Med 50 470-480. 

SETCHELL K D R and CASSIDY A (1999) Dietary isoflavones Biological effects and relevance to human health. J Nutr 129, 758S-67S. 

Relevance. A key criterion in the selection of biological indicators is relevance to human and ecological health and to the development of policy. Fish are directly relevant, for example, given that consumption of fish is the primary pathway for exposure to MeHg. The concentration of MeHg in fish is also a key variable in the issuance of fish-consumption advisories. 

Relevance to To ensure relevance to human Low Low Low Low in fresh Medium to High High and direct (/)... 

Criteria 1) Relevance to human health endpoints. 2) Sensitivity to change in loadings. 3) Overall historical data quality. 4) Data collection infrastructure. 5) Feasibility of data collection and analysis. 6) Ability to adjust for confounding factors. 7) Understanding of linkages with rest of ecosystem. 8) Broad geographic distribution. 9) Well-known life history (for fauna). 10) Nonintrusive sampling. 

Data concerning developmental toxicity in animals are very limited, and are at best suggestive that elicitation of developmental effects by some organophosphate ester hydraulic fluids may occur in some animals. The developmental toxicity data are too sparse to make any conclusions regarding their relevance to human health. 

The impairment of heme synthesis by lead has a far-ranging impact not limited to the hematopoietic system. EPA (1986a) provided an overview of the known and potential consequences of the reduction of heme synthesis as shown in Figure 2-11. Well documented effects are indicated by solid arrows, and effects considered to be plausible further consequences of the impairment of heme synthesis are indicated by dashed arrows. Additional discussion is provided in the following sections on renal and neurological effects. More detailed information on the exposure levels or blood lead levels at which these impacts may be experienced was provided in Section 2.2 and the relevance to human health is discussed in Section 2.5. 

The lead-induced nephropathy observed in humans and rodents shows a comparable early pathology (Goyer 1993). However, in rodents, proximal tubular cell injury induced by lead can progress to adenocarcinomas of the kidney (see Section 2.2.3.8). The observation of lead-induced kidney tumors in rats may not be relevant to humans. Conclusive evidence for lead-induced renal cancers (or any other type of cancer) in humans is lacking, even in populations in which chronic lead nephropathy is evident. 

Other carotenoids, such as canthaxanthin and astaxanthin have been recognized as potent inducers of CYP1A1 and 1A2 in rat liver (Gradelet et al., 1998). The administration of lycopene to rats was shown to induce liver CYP types 1 Al/2, 2B1/2, and 3A in a dose-dependent manner (Breinholt et al., 2000). The observation that these enzymatic activities were induced at very low lycopene plasma levels suggests that modulation of drug metabolising enzymes by carotenoids may be relevant to humans (Breinholt et al., 2000). 

Sensory quality can be defined as texture, flavour (taste), aroma and visual aspect. The sensory properties of milk are highly influenced by its fat content (Phillips et al., 1995a). As a result, research has examined the effects of various food additives on sensory quality when used as a substitute for fat in milk (Philips et al., 1995b). Frpst et al. (2001) showed that a combination of thickener, whitener and cream aroma in 0.1% fat milk was successful in mimicking the sensory quality of 1.3% fat milk. With the interest in the production of milk enriched with cis-9, trans-l 1 CLAs, owing to their relevance to human health (Tricon et al., 2004), recent research has examined the effects of CLA on the sensory quality of dairy products and found that it is possible to produce CLA-enriched dairy products with acceptable sensory characteristics (Jones et al., 2005). 

Earlier studies demanded calculation of an LD50 value (i.e. the quantity of the drug required to cause death of 50 per cent of the test animals). Such studies required large quantities of animals, were expensive, and attracted much attention from animal welfare groups. Its physiological relevance to humans was often also questioned. Nowadays, in most world regions, calculation of the approximate lethal dose is sufficient. 

BorghoffSJ. 1993. 2u-Globulin-mediated male rat nephropathy and kidney cancer relevance to human risk assessment. Chemical Industry Institute of Technology (CUT) Activities 1-8. 

Testicular interstitial cell tumors occur spontaneously in aged rats, and the incidence can vary greatly in control groups. This tumor is believed to be hormonally mediated. There was no evidence of malignancy in three rat studies and no evidence of this type of tumor in mice. It can be concluded that the tumorigenic effect, if real, is most unlikely to be relevant to human exposure [13]. 

Osimitz TG, Lake BG (2009) Mode-of-action analysis for induction of rat liver tumors by pyrethrins relevance to human cancer risk. Crit Rev Toxicol 39 501-511... 

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