Revival: Biological Effects of Low Level Exposures to Chemical and Radiation (1992)

6 BIOLOGICAL EFFECTS OF LOW LEVEL EXPOSURES

or possible to distinguish between the two. For example, is anxiety exoge­
nously induced? What dose constitutes overexposure to vitamin C? Are
saturated fats more injurious than unsaturated fats, and can consumption
of one over the other constitute toxicity? However, regardless of whether
instability results from senescence or toxicity, it manifests itself as injury,
inferred to be deleterious modification of vital system states.35

Hypothesis III: For homogeneous laboratory populations of eutherian
mammals housed under uniform, good laboratory conditions and kept free

of preventable disease, the hazard function is proportional to the mean level
of injury in the population.

This hypothesis comes from Sacher and Trucco;5’36-39 there exist both a
theoretical basis as well as experimental evidence in its support. It is a
powerful hypothesis, since it allows the time course of mean population
injury to be probed through mortality data. Mathematically, Hypothesis III

may be expressed as follows:

(5)

where k = a constant of proportionality

</>x = the mean level of injury in the population at time x

When multiple injury processes occur simultaneously (e.g., senescence and
toxicity), 0x is a weighted composite. Taking Napierian logarithms of
Equation 5, one obtains:

( 6 )

This is the generalized Gompertz function, previously posited as Equation
2, but now with an interpretation of </>x.
Application of this hypothesis assumes and requires both genetic and
environmental homogeneity, as well as good animal husbandry. Elements of
good animal husbandry include proper regulation of temperature, lighting,
heating, humidification, air quality, ventilation, hygiene, caging, handling,
bedding, water, diet and nutrition, etc.40 “Preventable disease” refers to
communicable disease (e.g., bacterial infection) as well as those caused by
unnecessary exposure to exogenous agents.

Hypothesis IV: For homogeneous laboratory populations of eutherian
mammals housed under uniform, good laboratory conditions and kept free
of preventable disease, the most commonly observed Gompertz function is
its linear form.

This hypothesis comes from Sacher.5 For applicable populations, it speci­
fies that senescent injury accrues at a constant rate. Data consistent with
this hypothesis have been observed by Boxenbaum, Neafsey, and col­
leagues,142425 28 and the thermodynamic approach of Yates8 supports this