FiTCHETT. — Physiological Action of Tutin. 327 



rabbit (Exp. 166) was given small doses of tutin by the mouth every third 

 or fourth day for nearly two months, the dose being gradually increased 

 up to 7 mlgm. per kilo (6 mlgm. per kilo is a fatal dose by the mouth in 

 rabbits). During this time the animal grew and developed normally, and 

 it increased in weight from 777 grams to 1,154 grams. This shows that 

 tutin does not retard growth. 



Another experiment was made on a guinea-pig (Exp. 167), the animal 

 being treated like the rabbit. A second guinea-pig, as a control, was kept 

 in the same hutch, and abundance of food was supplied. In thirteen days 

 the animal subjected to the influence of tutin gained 16 grams, and the 

 control in the same time gained 38 grams. The animals, however, were 

 not of the same age ; the control, being younger, apparently gained more. 



From these data it looks as if tutin had no injurious influence on general 

 metabolism (c/. Exp. 15, on a pigeon). 



15. Fate of Tutin in the Body. 



It is impossible to trace in the body the fate of a substance which, like 

 tutin, contains only C, H. and ; but that the tutin is not rapidly destroyed 

 or eliminated was shown by the following experiment (Exp. 13) : A guinea- 

 pig was given by mouth on alternate days a dose of tutin which was near 

 the minimum lethal dose ; thus, 1-5 mlgm. per kilo was given on the 17th, 

 on the 19th. and on the 22nd February. No symptoms appeared, so the 

 animal was able either to oxidize or to excrete this amount (1*5 mlgm. per 

 kilo) in two days. On the 24th it received 2 mlgm. per kilo, and a similar 

 dose w^as given on the 26th. On the 27th it was found dead. From this it 

 appears that a guinea-pig is unable to dispose of 2 mlgm. per kilo within 

 two days. Enough tutin must have been still present in the body on the 

 afternoon of the 26th, when the second dose of 2 mlgm. per kilo was given, 

 to raise the total amount present to the lethal dose. 



16. Immunity or Tolerance. 



Several experiments were made with the object of determining whether 

 tolerance of the effects of the poison can be estabUshed. 



A pigeon (Exp. 15) that had been subjected to gradually increasing 

 doses by mouth over a period of ten days withstood 16 mlgm. per kilo. 

 The minimum lethal dose in pigeons by oral administration is about 

 10"25 mlgm. per kilo. A second pigeon (Exp. 17), treated in the same 

 way for over three weeks, succumbed to 12 mlgm. per kilo. A guinea-pig 

 (Exp. 167), which was being treated in the same way, and had received 

 several small doses, was killed by a dose of 7*5 mlgm. per kilo given by 

 mistake, so that no great degree of tolerance had been estabUshed. A 

 rabbit, already referred to above when considering the effects on general 

 metabolism, received small doses, gradually increasing to 7 mlgm. per 

 kilo, over a period of two months. A dose of 8 mlgm. per kilo then caused 

 severe symptoms ; so that it would appear that a slight degree of tolerance 

 had developed, for the lethal dose, by oral administration, in rabbits is 

 about 7 mlgm. per kilo. Five days later this rabbit succumbed to a dose 

 of 11 '6 mlgm. per kilo per os. 



The general conclusion reached was that tolerance can be established 

 only in a very slight degree, if at all. 



