Ch. 7 — The Use of Animals in Testing • 157 
Mu tagenicity 
A mutation is a permanent change in a gene that 
is passed along to any descendants of the cell. Thus, 
mutations in germ cells will be passed along to off- 
spring. If recessive, the mutation will not be ob- 
served in the offspring but will become part of 
the gene pool from which future generations will 
draw . If the mutation is dominant , it may be lethal 
to the developing fetus or it might affect the off- 
spring in a variety of ways, including impairing 
its fertility. If the damage is to a somatic cell, the 
mutation could lead to cancer or, in a developing 
fetus, birth defects. 
There are several nonanimal and in vitro tests 
based on mammalian or human cells that would 
be considered alternative mutagenicity tests (see 
ch. 8). There are several whole-animal tests as well. 
One is the dominant lethal assay, in which a male 
is exposed to the test substance and then mated 
with an untreated female. Part way through the 
pregnancy, the female is killed and the number 
and condition of the fetuses observed. Another 
is the heritable translocation assay, in which the 
male progeny of treated males are mated with un- 
treated females and the effect on fetuses deter- 
mined. The mutations transmissible to the next 
generation are of special interest because of their 
implications for the human gene pool (5). 
The in vivo sister chromatid exchange and mouse 
micronucleus tests rely on microscopic examina- 
tion of the chromosomes themselves after the test 
substance has been administered to the whole ani- 
mal. In vitro versions of these techniques also exist 
(see ch. 8). Changes can be observed using a micro- 
scope. Host-mediated assays are a hybrid of non- 
animal and whole-animal techniques in which the 
test substance and a micro-organism are adminis- 
tered to an animal and the effects on the micro- 
organism determined (5). 
Current Trends 
Many factors are likely to influence testing prac- 
tices in the near future. Public pressure to use alter- 
natives to whole animals, increasing costs of using 
animals, and improvements in toxicological meth- 
ods are likely to reduce the use of some tests, such 
as the LD 50 and the Draize eye irritation tests . This 
pressure is also likely to result in changes in some 
existing tests in order to reduce animal suffering. 
These developments could bring about a review 
of current legal requirements for testing, perhaps 
reducing the amount of testing per chemical and 
the number of animals per test. Such a review, 
as well as advances in the state of the art, might 
better tailor testing to the substance being exam- 
ined and to the circumstances of human exposure . 
On the other hand, the number of substances be- 
ing tested could increase with greater regulatory 
or product liability requirements, with greater 
funding available for testing, or with less expen- 
sive tests available. 
Interpretation and extrapolation of test results 
to humans can be expected to improve as the mech- 
anisms of toxic responses are better understood. 
Increasing use of pharmacokinetics and mechanis- 
tic studies is likely to result in improved designs 
and better selection of tests. 
THE ROLE OF GOVERNMENT IN TESTING 
The Federal Government and each of the States 
are involved in testing in a variety of ways. Per- 
haps the most important are various explicit and 
implicit requirements for testing under existing 
statutes. Another area is the funding of research 
and development leading to new methods (see ch. 
12). Yet another is the funding of toxicological test- 
ing, conducted primarily by the National Toxicol- 
ogy Program (NTP), supported largely by the Na- 
tional Institute of Environmental Health Sciences. 
This program, chartered in 1978, is a cooperative 
effort among agencies within the Department of 
Health and Human Services (see chs. 11 and 12). 
Four principal Federal agencies have a signifi- 
cant role in animal testing for regulatory purposes: 
FDA, EPA, the Consumer Product Safety Commis- 
sion (CPSC), and the Occupational Safety and Health 
Administration (OSH A). Other agencies whose reg- 
ulatory activities affect animal use include the 
