MUTAGENS OF POTENTIAL SIGNIFICANCE 221 



In the male who drinks a few cups of coffee daily beginning at puberty, 

 we can calculate an induced mutant frequency of nearly 3 per cent by 

 age 30. ii, I 



If it is assumed that the average effect of radiation is to cause 

 approximately 10'^ mutations per gene per cell per r in man (56), it 

 follows that the calculated effect of caffeine on the stem line of 

 spermatogonia (p = 10"^'*) would be equivalent at age 30 to a cumula- 

 tive dose of about 50 r. This is in the range of what is considered to 

 be the probable doubling dose in man. A man who drinks as much as 

 10 cups of coffee daily would receive the equivalent of about 150 r. 

 Each cup of coffee would contribute about 0.003 r. During the first 

 trimester of pregnancy the effect on the fetus would be roughly 

 equivalent to about 3 r cumulative exposure for average (3-cup daily) 

 coffee intake during this critical period. 



I would say to Dr. Bcnzer that I hate to be put in this position. I 

 am not trying to argue anything for these assumptions. I think they 

 are so tenuous that they probably should not have been made at all. 

 But, in effect, this is what I was asked to do. There is a limited 

 amount of data, very little is known, so you either do something or not. 

 Perhaps it is more valuable not to do something until there are more 

 data to suggest what should be done. We will accept that as a 

 criticism. But I have chosen to do it the other way, to see what comes 

 out. I fully agree that these are very uncertain estimates. 



One can try the same calculations with Drosophila data. Andrew (1) 

 published on sex-linked lethals, in which he found that the effects of 

 caffeine were roughly equivalent to about 150 r for the doses he used, 

 which were quite high. 



In his first experiment he gave caffeine at 2500 mg/1 in the larval 

 food. The spontaneous rate was 0.14 per cent. He found 0.7 per cent 

 lethals in the progeny of males from one to 11 days old. In the 

 second experiment he gave a single injection of caffeine (probably 

 around 400 mg/kg) to adult males less than 24 hours old. Here he ob- 

 tained 0.6 per cent lethals, but no effect beyond the seventh day (brood 

 7). , , -I i 



Analysis of these data is difficult because in the first experiment we 

 cannot estimate the caffeine concentration to which the larval gonads 

 were actually exposed, since we know nothing about the rates of 

 metabolism and excretion of caffeine in this case. The maximum con- 

 centration possible would be that in the food; using this figure we are 

 likely to obtain a gross underestimate of the mutagenic efficiency of 

 caffeine. In the second experiment the exact dose administered is not 



