compound per kilogram of body weight. Accord- 

 ingly, all compounds were, if possible, force-fed 

 at a much higher initial dose, and thus the need 

 for further testing of most of them was eliminated. 

 Lethal compounds were retested at lower doses . 



Each chemical, in the gelatin capsules, 

 was force -fed initially to three fish. Additional 

 tests employed many more fish. The test fish 

 were removed from 47°F water, force-fed, 

 tagged, and placed in 65 °F running water for 

 observation. They quickly adjusted to this tem- 

 perature and sometimes attempted to feed 

 immediately. 



Dissection showed that gelatin capsules 

 in these fish held at 65°F disintegrated in approx- 

 imately 1 hour. That time would be required 

 before the chemical could come into contact with 

 the intestine (this would be true for most chem- 

 icals; several chemicals appeared to react with 

 the capsule and possibly contacted the intestine 

 more quickly). Therefore as a general rule 1 

 hour should be deducted from the time to effect 

 in table 1 . 



Fish that had been force -fed with one 

 chemical were often held with fish that contained 

 other chemicals. This mixing method was con- 

 sidered to be suitable under the circumstances, 

 since interesting chemicals were retested on 

 isolated fish. 



A few early tests were run for only 24 

 hours, but the minimum period for almost all 

 was 40 hours or more. Many fish were observed 

 for a number of days . 



Judging of effect was visual. If a fish 

 acted or looked other than normal it was con- 

 sidered to be sick. If no movement occurred it 

 was recorded as dead. Symptoms were noted, 

 and special attention was paid to possible pos- 

 itive directional movements . 



In table 1 the symbol for "less than" 

 (<) is used often to represent sickness, recovery, 

 or death occurring before the time of observation. 

 The symbol for "more than" (>) is used occasion- 

 ally to represent doses where exact data are for 

 one reason or another lacking. 



DISCUSSION OF TOXICITY AND 

 SYMPTOMS OF TOXICITY 



That a detailed analysis of the relative 

 toxicity of compounds and groups of compounds 

 tested would be meaningless will become appar- 

 ent if table 1 is carefully examined. It appears 

 that the toxic compounds in different groups 

 affected fish without rhyme or reason. This is 

 not entirely true since some groups included 

 many toxic compounds while others contained 

 very few. There are physiological reasons for 

 effect or lack of effect of compounds on fish but 

 these are little known. So far the attempt to 

 relate toxicity to molecular mechanisms has 

 succeeded in only a few cases (Adams, 1959). 

 These few include determination of the effects 

 of carbon monoxide, cyanide, the reversible 

 anticholinesterase poisons physostignine and 

 neostigmine, the irreversible organic phosphates 

 isopropylflurophosphate (DFP), tetraethylpyro- 

 phosphate (TEPP), and others, the protein se- 

 creted by the botulinus bacillus which disrupts 

 the acetylcholine cycle, and flouroacetic acid 

 which interferes with the citric acid cycle. 

 Nevertheless, the metabolic targets of most 

 compounds remain uncertain, and most common 

 poisons such as nicotine and arsenic are incom- 

 pletely understood. Therefore results of the 

 tests presented in table 1 cannot be explained 

 adequately and, in fact, in most cases cannot 

 be explained at all. 



The apparent randomness of effect illus- 

 trated in table 1 is more easily understood if it 

 is remembered that physiological action is highly 

 dependent on details of structure. An example 

 would be the "Lindane" series (page 109) where 

 only the delta isomer produced an effect. Cer- 

 tain compounds in a group might readily produce 

 symptoms while others, apparently close related, 

 produce none. An example of the manner in which 

 activity can be changed by structural variation is 

 the following from Albert (1960): The vitamin 

 activity of thiamine drops to 5 percent if the 

 methyl group is removed from the pyrimidine 

 ring, to less than 1 percent if the methyl group 

 is removed from the thiazole ring. If an extra 

 methyl group is inserted into the thiazole ring 

 between nitrogen and sulfur the vitamin activity 

 completely disappears . That there are many 



