degrees depending on the specific
phenethanolamine. The lipolytic and
lipogenic effects of phenethanolamines on
adipose tissue are facilitated by activation
of -adrenergic receptors and may be
transient due to receptor desensitization or
down-regulation. -Adrenergic receptors
may also be involved in the muscle protein
accretion effects of phenethanolamines, but
definitive data showing this mechanism
of action in livestock remain elusive.
Phenethanolamines studied in livestock
activate 1- and 2-adrenergic receptors,
but classification of receptor subtype
specificity has been based primarily on
data from rodent and human receptors. It
has become increasingly evident that
species differences exist in the pharmaco-
logy of -adrenergic receptors and that a
full understanding of phenethanolamine
binding and activation will only occur
when evaluated in the species of interest.
Further research is needed to better define
the relationship of 1- and 2-adrenergic
receptors, as well as other receptors and
pathways, to the anabolic effects of
phenethanolamines in livestock.Safety and Residue Issues
Detailed safety and residue testing is
required on any repartitioning agent that is
developed for use in meat animals. These
tests are directed toward human food
safety, safety to the environment and safety
to the animals of intended use (target
animal safety). For example, effective doses
of ractopamine were reported to have
negligible to undetectable residue levels in
swine (Dalidowicz et al., 1992; see
Anderson et al., 1993), and zilpaterol
residues in cattle were well below the
threshold that posed any human health
risk (Zilmax Technical Manual, 1998).
Extensive reviews of safety and residue
data by regulatory agencies will ensure that
phenethanolamines are cleared for use
only if all safety questions have been
answered to the satisfaction of the Food
and Drug Administration (FDA) and other
regulatory agencies.The phenethanolamine clenbuterol
was the subject of considerable negative
publicity in the early 1990s when its illegal
use and indiscriminate misuse was linked
to cases of acute food poisoning (Martinez-
Navarro, 1990; Pulce et al., 1991; Salleras
et al., 1995) and illegal show-ring use.
People in France (Pulce et al., 1991) and
Spain (Salleras et al., 1995) who suffered
from food poisoning after consumption
of contaminated liver from livestock
fed clenbuterol reported symptoms of
tachycardia, tremor, headache and dizzi-
ness. At the 1995 EU Scientific Conference
on Growth Promotion in Meat Production
(Brussels), it was concluded that large-
scale application of pharmacologically
potent agents for growth-promoting
purposes should not be recommended
because of the potential for misuse leading
to adverse health effects in humans. In
March 1996, the EU banned the use of
-adrenergic receptor agonists (Directive
96/22/EC), and national monitoring
programmes have been put in place to
eliminate their illegal misuse (see Kuiper et
al., 1998).
In the USA, the illegal use of
clenbuterol has been limited primarily to
show animals. Reports of illegal use of
clenbuterol to increase muscle and reduce
fat mass, combined with the association
between clenbuterol residue and food
poisoning, led to the development of sensi-
tive assays for the detection of clenbuterol
and other -adrenergic receptor agonist
residues (see Mitchell and Dunnavan,
1998). The identification of clenbuterol
residues and subsequent disqualification of
champion steers, lambs and barrows at the
Tulsa State Fair and National Western
Stock Show led to an increased awareness
of the illegal use of clenbuterol. Since that
time, several convictions have been made
for illegal distribution of clenbuterol
(Mitchell and Dunnavan, 1998). Clearly,
the misuse of clenbuterol needs to
be closely monitored and eliminated.
However, other phenethanolamines have
the potential to improve the efficiency of
livestock production without adverse
effects on human health.Phenethanolamine Repartitioning Agents 8504 Farm Animal Metabolism 04 20/4/00 12:02 pm Page 85