administration. The drug does not remove all worms, of course, and it is apparently 
therapeutically ineffective in animals whose digestive function is seriously impaired, It 
is little wonder that there is concern over practical failures of phenothiazine when one 
considers the wide and almost exclusive reliance on it as a panacea for gastrointestinal 
parasitism! Notwithstanding its shortcomings, we are nevertheless confident, despite 
imperfect knowledge of the balance sheet, that the chemical presents no consumer hazard, 
The fate of orally administered phenothiazine has been studied in man, cattle, sheep, 
horses, pigs, dogs, rabbits, and rats. Derivatives have been identified in the alimentary 
tract, feces, blood, urine, and aqueous humor, At least eight catabolic or excretion 
products have been identified, namely, unchanged phenothiazine, leucophenothiazone,. 
potassium leucophenothiazone sulfate, phenothiazone, leucothionol, leucothionol glu- 
curonide, thionol, and phenothiazine sulfoxide. There is also a compound inthe urine of 
treated animals which is said to yield the parent substance upon acidification, and a 
polypeptide conjugate in the urine of cattle. Information on the fate of phenothiazine in 
any one species of animal is incomplete, but the aggregate information on all species 
shows that detoxication is relatively complicated, with somewhat differing mechanisms 
in different species of animals but without much distortion or breakdown of the parent 
molecule, Derivatives vary also with age and dose rate within a single species. Kind of 
food may exert some influence, at least quantitatively. Thionol is apparently the end 
result of the detoxication mechanisms inallanimals, This is a conspicuous red dye, which 
is at least helpful in determining the rate of elimination. So far as determined, pheno- 
thiazine and its derivatives are completely eliminated from the animal body in about 4 
days. The intermediates, incidentally, although not far removed from phenothiazine, are 
evidently not toxic to either the host or its parasites. The only exception seems to be 
phenothiazine sulfoxide which has anthelmintic properties and is responsible for occasional 
photosensitization keratitis in cattle, and possibly also forthe same phenomenon in sheep 
and goats. 
As of today, legislation has made antiparasitics suspect, and some even outlawed, 
but this is scarcely the major concern in the area of protozoan and helminthic parasites, 
Safety has long been the definitive criterion, not only for reasons that are evident, but as 
prudent policy in conformity with responsibilities of Federal regulatory agencies. Indeed, 
safety to consumers as a factor inthe standardization of antiparasitics anticipated present 
legislation in the instances ofarsenic, lead, fluorine, and cadmium, all uses of which were 
adjudged as of thetime to be without consumer hazard. This is of record, However tenuous 
the grounds, it could be argued that antiparasitics,as recommended for use today, are as 
safe from a consumer standpoint as our public water supply. 
Problems are inordinately real and obvious; they have been heralded by previous 
discussion. Most significant is that of finding the road back to the scientific method in the 
development of control measures. A few investigators have emphasized the seemingly 
irrefutable fact that knowledge of mechanism of drug action, physiology of parasites, 
biology of parasitisms, and especially the delicate adjustments thereof, are the basis on 
which to build, Chemotherapy arose during what might naively be called the ‘‘golden age”’ 
of biochemistry when many chemists turned their attentions to living things, to the effects 
of chemicals on them, to the chemistry and fate of foreign chemicals in the animal body 
and, significantly, to the concept and study of selectively toxic action of chemicals on 
closely associated but differing species of living organisms. Selective toxicity is the 
epitome of problems that want for elucidation in chemical attack on living things. The 
road back to this concept is not readily apparent. 
Problems of antiparasitics are comprehensive. Immediate problems are evident--all 
referable to basic criteria of safety, efficiency, use, and cost. But the real problem is para- 
sitism--the true substance of parasitology--a way of life that characterizes the majority of 
kinds and numbers of living things. While animal parasitology has traditional roots inthree 
or four phyla of the animal kingdom, modern parasitology has become increasingly oriented 
about parasitism as a biological phenomenon. What do parasites do? Why are they parasites? 
How do they live? These are the questions being asked. We know little, for example, 
about the role of parasites as vectors and reservoirs of pathogens, as agents and 
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