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5,3 TOXICITY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEMICAL COMPOUNDS 329

TABLE 5.24 Toxicity Studies for Safety Evaluation of Drugs, Pesticides, Food
Additives, and Other Chemicals Utilizing Experimental Animals and Other
Systems Required by Health Authorities

Name of study Animal species Duration of study Reason for study
Biotransformation Rats/mice One day to weeks Metabolism
Kinetic studies Rats/mice One day to weeks Absorption, distribution,
and elimination
Acute toxicity Rats/mice 2 weeks Acute effects
Subacute toxicity Rats/mice 2-3 weeks Delayed effects,
target organs
Suhchronic study Rats/mice/dogs/rabbits 6 months Target organs,
delayed effects
Chronic studies Rats/mice 1 8-24 months Chronic effects of
low exposures
Carcinogenicity Rats/mice 18-24 months Carcinogenic potential
Teratogenicity Rats/rabbits 3-4 weeks Teratogemc potential
Reproductive Rats/mice/rabbits Several months Potential to affect
toxicity reproduction
Irritation Rats/rabbits Few days Irritation index
Sensitization Guinea pigs/rats Few weeks Potential to sensitize
Mutagenicny, Rats, mice, bacterial Few days Potential to cause mutations,
genotoxicity strains, yeasts chromosomal damage, and
other genotoxic effects

one to compare a dose that causes a toxic effect in an experimental animal
with the human dose in an occupational setting or general environment. This
is vital because, in most cases, assessment of toxicity, e.g., hazards of new
chemicals, is based purely on experimental animal studies. Assessment of ex-
posure in the occupational environment relates the human situation to the
toxicity data derived from experimental animal studies.
In risk characterization, step four, the human exposure situation is compared to
the toxicity data from animal studies, and often a safety-margin approach is utilized.
The safety margin is based on a knowledge of uncertainties and individual variation
in sensitivity of animals and humans to the effects of chemical compounds. Usually
one assumes that humans are more sensitive than experimental animals to the effects
of chemicals. For this reason, a safety margin is often used. This margin contains two
factors, differences in biotransformation within a species (human), usually 10, and
differences in the sensitivity between species (e.g., rat vs. human), usually also 10.
The safety factor which takes into consideration interindividual differences within
the human population predominately indicates differences in biotransformation, but
sensitivity to effects of chemicals is also taken into consideration (e.g., safety factor of
4 for biotransformation and 2.5 for sensitivity; 4 x 2.5 = 10). For example, if the
lowest dose that does not cause any toxicity to rodents, rats, or mice, i.e., the no-ob-
servable-adverse-effect level (NOAEL) is 100 mg/kg, this dose is divided by the
safety factor of 100. The safe dose level for humans would be then 1 mg/kg. Occa-
sionally, a NOAEL is not found, and one has to use the lowest-observable-adverse-
effect level (LOAEL) in safety assessment. In this situation, often an additional un-