Sentinels, animals

If animal testing is required, a full-scale Draize test may not be necessary given the background established in the beginning of the tier approach. For instance, the compound could be tested in a single sentinel animal to obtain confirmation of in vitro data. In addition, other modifications could be used, such as the administration of appropriate anesthetics to the test animals, or the use of the low-volume Draize modification (Falahee et al., 1982 Freeberg et al., 1984 Griffith, 1987). 

Mansonia mosquitos as well as some ticks, with birds as intermediate hosts (see Table 23.7—Clinical Profile of West Nile Fever). Historically, WNV was endemic to Africa, West Asia, and the Middle East. Scientists from the CDC believe the virus migrated to the eastern United States in the summer of 1999 or possibly earlier. The continued expansion of the virus in the United States indicates that it is permanently established in the Western Hemisphere (refer to Figure 23.7—2005 West Nile virus activity in the United States.). In the temperate zones, cases occur primarily in the late summer or early fall, whereas in the southern climates the virus can be transmitted year round (CDC, 2005e). Birds, mosquitoes, and equines serve as sentinel animals that could alert health officials to the occurrence of human disease. 

Lewisite has the potential to cause skin lesions in any species but the risk is greatest in hairless animals such as pigs, and decreases in fur-covered species (Smith, 1997). Mice and rats appear to be almost twice as susceptible to dermal lewisite exposures than humans (LD50 equals 12,15, and 30 mg/kg, respectively) (DeRosa et al, 2002 RTECS, 2008 Sidell et al, 1997). More studies are needed to determine if rodents would be good sentinel animals. 

Dogs may be good sentinel animals as they appear to have increased susceptibility relative to humans based on physiological differences. More controlled studies are required, however. 

Mouse Groups of 50 male and 50 female B6C3Fi mice, eight weeks of age, were administered skin applications of 0, 88 or 177 mg/kg bw 2,3-dibromo-l-propanol (98% pure) in 95% ethanol on five days per week for 36-39 weeks (males) or 39-42 weeks (females). The study was terminated at 36-39 weeks (males) and 39 2 weeks (females) because sera from sentinel mice housed in the same room as the study animals were found to be positive for antibodies to lymphocytic choriomeningitis virus. As shown in Table 1, increased incidences of skin papillomas, forestomach papillomas and forestomach carcinomas were observed in both sexes. Hepatocellular adenomas were seen in 1/50 control, 2/50 low-dose and 9/50 high-dose p < 0.05) male mice no data for liver were reported in females (Eustis et al., 1995). 

Sentinel Sentinel systems can take several forms. One type of sentinel system used by the CDC collects data on selected diseases from predetermined groups of health care providers or institutions. An example is the primary care provider network that supplies weekly information on influenza activity (CDC, 2004e). Another type of sentinel system involves periodic monitoring of specific animal or insect populations for evidence of certain infections (CDC, 1992). 

An often over-looked aspect of surveillance for bioterror events is surveillance of animal populations. Several of the agents considered to have bioterror potential are diseases of animals, for example, anthrax and brucellosis (Franz et al., 2001 Inglesby et al., 1999 USAM-RIID, 2005). A covert attack may first become apparent when animals become ill. The need to coordinate information from medical and veterinary sources was illustrated by the epidemiologic investigation during the 1999 West Nile Virus outbreak in New York City. Investigators found that there had been an outbreak in birds several weeks prior to the human outbreak (Fine Lay-ton, 2001). The current surveillance plan for monitoring West Nile Virus infection in the U.S. includes sentinel surveillance of several animal populations (CDC, 2003). 

There are no controlled studies showing that any species of animal would make a good sentinel for phosgene oxime exposure. 

Rabinowitz, P., Wiley, J., Odofin, L., Wilcox, M., Dein, F.J. (2008). Animals as sentinels of chemical terrorism agents an evidence-based review. Clin. Toxicol. 46 93-100. 

Human health biomonitoring may also use animal surrogates in the environment to assess potential health hazards to humans - the proverbial canary in the coal mine . For example, chemical and biomarker analysis of bodily fluids or tissue biopsies from family pets, especially dogs, are sometimes used to assess potential chemical exposure and effects in children. This is because dogs often accompany children in the outdoor environment, and both have a tendency to (accidentally or intentionally) consume environmental media such as soil and surface water There has also been an increasing trend to use native animals as sentinel species, that is, fish, wildlife, or invertebrates that are indicators of possible human health risks from environmental hazards. For example, increased incidences of tumors or endocrine disruption in fish may indicate the presence of compounds in the water that may cause cancer or reproductive dysfunction in humans. Concern has also been raised over the increased incidence of deformities in frogs, because these may indicate an increased level of chemicals in the environment, which can cause birth defects in humans. 

Aged Rat Study. Using the sentinel rats in the 2-year study, 15 male and 15 female rats (18 months old) shall be gavaged at the middle dose. Blood samples shall be taken at five time points (to be specified by NTP), with three animals bled at each time point. Each rat shall be bled only once. Test chemical concentrations shall be determined in plasma using a validated analytical method. 

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