Sayre 12.01 per cent, Kennedy 20 per cent, O'Brine 12.15 per cent, while
the sample analyzed by the Bureau of Chemistry gave 18.4 per cent of
ash. One sample from Kit Carson County, Colo. (December, 1906), which
proved inactive physiologically, gave an ash content of 6.9 per cent. A
sample of _Astragalus missouriensis_ collected at Hugo, Colo., June,
1907, yielded an ash content of 21.8 per cent, and an _Astragalus
missouriensis_ collected at Pierre, S. Dak., September, 1907, yielded 27
per cent. An _Astragalus nitidus_ from Custer, S. Dak. (July, 1907),
gave 5.2 per cent ash, while an _Astragalus nitidus_ collected at
Woodland Park, Colo., in October, 1906, yielded 7.8 per cent, and
another specimen of _Astragalus nitidus_ also collected at Woodland
Park, Colo., in October, 1907, gave 12.2 per cent. An _Astragalus
drummondii_ from Custer, S. Dak. (July, 1907), gave 5.9 per cent.
_Astragalus pectinatus_ (Hugo, June, 1907) yielded 6.1 per cent. A fresh
(undried) specimen of _Astragalus mollissimus_ (unknown origin,
November, 1907) yielded 3.8 per cent of ash. One sample of _Astragalus
decumbens_ (Ephraim, Utah, August, 1907) gave 21.8 per cent of ash.
These determinations must necessarily be only approximate, as the plants
were collected by different persons who exercised different degrees of
care in freeing them from adherent soil, and possibly in drying the
plants, so that the main value of these figures is their aid in
determining the amount of barium present.
* * * * *
FOOTNOTES:
[185] The detailed analysis of O'Brine can be found on page
32 of this report.
[186] All ash and barium determinations were made from the
dried plants save when otherwise specified.
[187] Evidently these plants must have been imperfectly freed
from soil.
=BARIUM DETERMINATIONS IN THE ASH OF LOCO PLANTS.=
Attention has been called to the fact that in ashing plants containing
barium a part at least of this barium is converted into the insoluble
sulphate and a part into the carbonate, so that the characteristic
pharmacological action of the ash will depend not upon the total barium
present, but upon the form in which it occurs--little action if much
BaSO_{4}, and more complete if more BaCO_{3} results. A further
difficulty in the recognition of barium in plants is due to the fact
that certain inorganic salts interfere with the precipitation by
H_{2}SO_{4}.
A specimen of _Aragallus lamberti_ (Hugo, summer of 1907) with 12.44 per
cent of ash was examined for its barium content by Hillebrand's
method.[188] The method was as follows:
Two grams of the ash were first fused with sodium carbonate and the
fused mass washed with water containing sodium carbonate. The residue
was washed into a beaker and treated with a few drops of sulphuric acid.
The residue now remaining was filtered and after ignition was treated
with hydrofluoric and sulphuric acids. After evaporating off these
acids, the residue was treated with sulphuric acid water, filtered, and
then fused with sodium carbonate. After extracting with sodium carbonate
water, the residue was dissolved in just enough hydrochloric acid and
precipitated with sulphuric acid. The precipitate was dissolved in
concentrated sulphuric acid and reprecipitated by water and weighed as
BaSO_{4}.[189] So far as the writer can ascertain, there have been no
control experiments made for this method to determine the experimental
error.
Of the above ash, 1.998 grams gave 5.2 milligrams of BaSO_{4}, which
would correspond to 75.75 milligrams of barium acetate crystals--
Ba(C_{2}H_{3}O_{2})_{2}+H_{2}O--in 200 grams of the dried plant. The
residue by the Hillebrand method after weighing was tested with the
spectroscope and gave a bright spectrum for barium. The same ash was
analyzed by the Bureau of Chemistry, using a shorter method, and they
reported 2.7 milligrams of barium sulphate in 1.1217 grams of ash. A
second sample collected earlier in the summer, with an ash content of
18.6 per cent, was shown to yield barium corresponding to 3.4 milligrams
of BaSO_{4} in 2.5 grams of the ash.[190]
One lot of _Aragallus lamberti_ collected at Hugo, Colo., in May, 1905,
and which gave an ash content of 37.3 per cent, was found to yield 3
milligrams of BaSO_{4} from 1.998 grams of ash, or 173.88 milligrams of
Ba(C_{2}H_{3}O_{2})_{2}+H_{2}O in 200 grams of the dried plant, but this
ash also contained 0.27 per cent of SO_{3}. The Bureau of Chemistry
reported the barium to correspond to 2.9 milligrams of BaSO_{4} in 2.45
grams of the ash.
The _Astragalus missouriensis_ (Hugo, June, 1907), with an ash content
of 21.8 per cent, gave 3 milligrams of BaSO_{4} in 2.01 grams of ash,
or 76.58 milligrams of Ba(C_{2}H_{3}O_{2})_{2}+H_{2}O in 200 grams of
the dried plant. The residue after weighing was tested spectroscopically
and gave a bright barium spectrum.
The _Astragalus drummondii_ from Custer, S. Dak. (1906), _Astragalus
mollissimus_ from Kit Carson County, Colo. (December, 1906), and
_Astragalus nitidus_ from Woodland Park, Colo. (October, 1907), were
reported by the Bureau of Chemistry to contain no barium.
The ash of the _Astragalus pectinatus_ (Hugo, June, 1907) was reported
by the Bureau of Chemistry to show no barium on spectroscopic
examination.
Two grams of active loco plant ash yielded from 5 to 6 milligrams of
BaSO_{4}, but it can be easily seen that in multiplying this amount to
correspond to 200 grams of the dried plant errors would be likely to
arise, so that the whole amount of barium would not necessarily be
accounted for.
* * * * *
FOOTNOTES:
[188] Hillebrand, W. F. Analysis of Silicate and Carbonate
Rocks. U. S. Geol. Surv. Bul. 305, p. 116. 1907. See also
Folin, O., On the Reduction of Barium Sulphate in Ordinary
Gravimetric Determinations, in Journ. Biol. Chem., vol. 3, p.
81. 1907.
[189] All the determinations of barium which resulted either
positively or negatively were made with the same bottle of
sodium carbonate and H_{2}SO_{4}, so that impurities in the
chemicals were thus eliminated.
[190] Report from Bureau of Chemistry.
=ANALYSIS OF SOILS.=
One sample of the soil from near Hugo, Colo., from which the _Aragallus
lamberti_ was collected, was examined by the Bureau of Soils, and that
Bureau reported the absence of barium and zirconium, at least of any
recognizable by the chemical methods used, so that it can not be said
that the barium came from any soil accidentally mixed with the ash.
Traces of titanium were, however, found. Evidently the plant must
collect minimal quantities of these elements from the soil and store
them.
The water from a well of an adjacent area was examined by the Bureau of
Chemistry and reported to contain 37.4 parts of calcium and 13.7 parts
of magnesium in one million, and that the water contained no
barium.[191]
* * * * *
FOOTNOTES:
[191] Barium has been found in well water in England. See
Thorpe, T. E., Contribution to the History of the Old Sulphur
Well, Harrogate, in Philos. Mag., 5 s., vol. 2, p. 50, 1876.
=FEEDING EXPERIMENTS WITH BARIUM SALTS ON ANIMALS IN THE LABORATORY.=
On these figures the writer took 0.2 gram of crystallized barium acetate
c. p., using the acetate because acetic acid has been proved in certain
loco plants by Power and Cambier, and after dissolving it in water fed
it at 9.45 a.m. to a rabbit weighing 1,177 grams. The head soon fell
forward so that the nose rested on the ground. At 10.58 a.m. the rabbit
seemed unable to guide itself and would run into obstructions if forced
to move. There was no diarrhea but it urinated several times. There was
a peculiar tremor of the muscles noted. The animal would not startle by
sudden noises and at 11.06 a.m. could be placed on its back with ease.
The pupils appeared about normal. The whites of the eyes showed very
prominently. At 11.35 a.m. the fore legs were paralyzed. The following
morning the animal was dead, its weight being 1,120 grams. The heart was
dilated; the stomach was not hemorrhagic, but rather pale.
A second rabbit, which weighed 1,630 grams, was fed with a solution of
0.5 gram of the same salt at 9.42 a.m. At 10.35 a.m. the animal passed
soft stools and showed a marked disinclination to move, with evidence of
pain. The diarrhea[192] became more marked and the animal's hind
quarters were soiled with feces. At 10.48 a.m. there was marked
incoordination of the limbs and inability to stand. Finally, at 10.56 a.
m., convulsions began and the animal died at 11.02 a.m. The autopsy was
made about two hours later. The animal was then rigid. The kidneys
seemed rather congested. The intestines were relaxed; mesenteric vessels
dilated. The pyloric region of the stomach appeared hemorrhagic.
A third rabbit, fed like the preceding with 0.5 gram of barium acetate,
showed much the same result. In this case there was some retching, but
the other symptoms were as above, the animal dying in one hour and five
minutes. No hemorrhages were seen in the stomach walls. It was noted
that after the administration of certain doses, 0.2 gram, there was no
diarrhea.
On September 23, 1907, a rabbit weighing 1,757 grams was fed at 10.42 a.
m. with 0.1 gram of the same barium acetate. The temperature at the time
of feeding was 102.9°F. At 12.05 a.m. the animal urinated.
Temperature, 101.4°F. On September 24 the animal weighed the same.
Temperature at 10.55 a.m., 102.3°F. The same amount of barium was fed.
At 3.40 p.m. the temperature was 102.5°F. On September 25 the animal
weighed 1,800 grams. Temperature, 102.2°F. at 10.39 a.m. The dose of
barium was repeated. At 3.55 p.m. the temperature was 101.4°F. On
September 26 at 9.38 a.m. the temperature was 101.1°F., and again the
barium was given. At 3.57 p.m. the temperature was 101.5°F. On
September 27 the rabbit weighed 1,772 grams. The temperature at 9.53 a.
m. was 102.3°F. The barium was fed for the fifth time. At 10.27 a.m.
there were general convulsions. The eyes teared. At 10.32 a.m. soft
stools appeared and the animal urinated. Stools were passed at various
periods. At 11.30 a.m. there were no signs of pain on pinching the ear.
At 11.58 a.m. the animal retched. The animal was lying with the fore
legs wide apart and could not support itself. At 12.05 p.m. the
temperature was 98°F. and the rabbit died shortly after.
The peritoneal cavity seemed normal. The small intestines were relaxed,
while the mesenteric vessels were dilated. The kidneys seemed congested.
The stomach walls were pink and in places covered with mucus. The heart
was relaxed save the left ventricle, which seemed firm.
On September 23, 1907, a second rabbit, weighing 1,360 grams, was fed
with a similar solution and the feeding was repeated at the same time
the first rabbit was fed. On September 27 the animal weighed 1,416
grams. On this day a peculiar movement of the hind legs on jumping
appeared, apparently due to an inability to draw the legs completely up,
and the fore legs were spread wide apart, as if too weak to support the
animal. The temperature had also fallen. On September 28 the animal had
apparently recovered. Weight, 1,516 grams on October 21.
On September 23, 1907, a third rabbit, weighing 1,304 grams, was fed
with 50 milligrams of barium acetate. This dose was repeated each time
the other two rabbits were fed. On September 27 it weighed 1,304 grams.
Marked muscular twitching appeared, with disinclination to move. Finally
there were convulsions and paralysis of the limbs. No stools were seen.
This animal lay quiet all night, apparently unable to move, and
continued on its side until 3.15 p.m. on September 28, when it
gradually recovered, weighing 1,346 grams on October 24.
On October 24, 1907, a rabbit weighing 1,346.5 grams was fed with a
solution of 25 milligrams of crystallized barium acetate. On the next
day the weight was 1,318 grams, and the dose was repeated. On October 26
it weighed 1,275.7 grams, and the dose was repeated; on October 30 it
weighed 1,332 grams, and on October 31 its weight was 1,375 grams. The
animal died at night on November 6; weight, 1,134 grams. The post-mortem
examination, made with Dr. Meade Bolton, of the Bureau of Animal
Industry, was negative save for the presence of necrotic tissue in one
enlarged thyroid.
On October 24, 1907, a rabbit weighing 1,332 grams was fed with a
solution of 25 milligrams of crystallized barium acetate. On the next
day the animal weighed the same, and the dose was repeated. On October
26 it weighed 1,289 grams, and the same amount of barium was given. On
October 28 the weight was 1,219 grams and two days later 1,289 grams.
On October 31, 1907, a rabbit weighing 723 grams was fed with a solution
of 25 milligrams of barium acetate. This rabbit was fed in all nine
times during a period of ten days. At the end of this time it weighed
779 grams and died six days later, weighing 723 grams. The post-mortem
was negative.
A rabbit weighing 779 grams was also fed on October 31, 1907, with a
similar amount of barium. This dose was repeated six times during an
interval of eight days. At the end of that time the animal still
retained its normal weight. On November 14, 1907, it weighed 709 grams,
having lost 70 grams. Thus after daily doses of 0.1 gram of crystallized
barium acetate no symptoms appeared until the fifth day, when death
resulted. After the similar administration of 50 milligrams severe
symptoms developed on the same day, but the animal recovered. After the
administration of 25 milligrams on three successive days the animal
died. In other cases of feeding 25 milligrams for several successive
days, some lost weight and died; others merely lost in weight, but
recovered.
Bary fed a rabbit weighing 0.9 kilogram a solution of 30 milligrams of
barium chlorid on one day, on the second day 90 milligrams, and on the
third day 30 milligrams. The only symptom noted was diarrhea. The animal
died on the fifth day. In other words, after feeding small doses of
barium salts for several days acute symptoms suddenly set in, showing a
cumulative action. This cumulative action has been noted on man.[193]
Onsum[194] fed a medium-sized rabbit daily with small doses of barium
carbonate, beginning with 20 milligrams. When the total amount reached
0.19 grams the rabbit died. The animal before death showed paralysis,
respiratory disturbances, and fall in temperature. The sensibility of
the cornea diminished, but the pupils responded to light. The stomach
walls showed ecchymoses and the blood vessels of the brain, the spinal
cord, and the abdominal vessels were dilated. Emboli in the pulmonary
arteries were also noted.
In a rabbit the application of 0.66 gram of barium chlorid to a wound
was followed in twenty minutes by convulsions, paralysis, and finally
coma and death.[195]
Of barium nitrate 0.66 gram mixed with sugar and fed to a rabbit caused
death in less than one hour, and 0.33 gram induced death in another
rabbit in twenty-seven hours.[196]
Six grains (0.4 gram) of barium iodid fed in solution to a rabbit caused
death the following day. On this day there were tremors of the neck and
shoulders with convulsive movements of the limbs. There was also
grinding of the teeth. "The mucous membrane of the stomach was rose-red
at the cardia, and softened." Membranes of the cord and brain also were
congested.[197]
For rabbits weighing 1,500 to 2,000 grams the lethal dose of barium
chlorid on subcutaneous use is stated to be 0.05 to 0.06 grams.[198]
A rabbit weighing 1,106 grams was fed with a solution containing 50
milligrams of crystallized barium acetate c. p. and 50 milligrams of
zirconium chlorid (pure). In fifty-seven minutes the animal showed
difficulty in moving the fore legs, developing marked paralysis of the
same about five hours later, and died the following morning--that is,
twenty-two hours after feeding. The heart was found dilated, kidneys
congested, stomach walls pink and covered in places with mucus and
partly digested blood, and cerebral dural vessels dilated, but no clots
were seen; bladder full.
Mixtures of 0.5 gram of calcium acetate and 50 milligrams of barium
acetate failed to kill. Mixtures of titanium and barium were not tried,
as no titanium salt soluble in water and of neutral reaction was
accessible.
Mittelstaedt called attention to the fact that pregnant rabbits were
more easily affected by the barium administration than nonpregnant ones,
and noted abortion in one case.[199]
One gram of the barium carbonate killed a dog in eight hours. A second
dog died in fifteen hours. Both of these animals vomited so that a
portion of this must have been lost.[200] Barium carbonate was formerly
employed as a rat poison.[201]
Of barium chlorid 0.6 gram, fed in aqueous solution, caused death in a
dog in forty-eight minutes if vomiting was prevented.[202]
In Tidy's hands 2 grams of the barium nitrate caused death in a small
terrier in three and three-fourth hours. This dog had slight
convulsions, was almost unable to stand, and had vomiting and purging.
The reflexes were diminished. A small dog recovered only completely in
five days after being fed 0.66 gram, while a large dog after being fed
1.3 grams only recovered after two days.
In cats 0.8 gram of barium carbonate when introduced into a wound caused
on the third day languor, slow respiration, feeble pulse, twitching of
hind legs, dilated pupils, and death.[203]
* * * * *
FOOTNOTES:
[192] Magnus, R. Wirkungsweise u. Angriffspunkt einiger Gifte
am Katzendarm. Archiv. f. Gesam. Physiol., vol. 108, p. 44,
1905.
NOTE.--Reports on the histological changes in acute barium
poisoning can be found in Pilliet, A., and Malbec, A. Note
sur les Lesions Histologiques du Rein Produits par les Sels
de Baryte sur les Animaux. Comp. Rend. Hebd. Soc. de Biol.,
vol. 4, p. 957. 1892.
Literature on the pharmacology of barium not otherwise
referred to is as follows: Boehm, R. Ueber d. Wirkungen d.
Barytsalze auf d. Thierkörper. Arch. f. Exp. Path., vol. 3,
p. 217. 1875.--Sommer, F. Beitr. z. Kennt. d.
Baryum-Vergiftung. Dissert., Würzburg, 1890.--Neumann, J.
Ueber den Verbleib der in den thierischen Organismus
eingeführten Bariumsalzen. Archiv. f. Gesam. Physiol., vol.
36, p. 576. 1885.--Hefftner, A. Ausscheidung körperfremder
Substanzen im Harn, Ergeb. d. Physiol., pt. 1, p. 121.
1903.--Binet, P. Recherches Compar. sur l'Action Physiol. des
Métaux, Alcalins et Alcalino-terreux. Rev. Méd. de la Suisse
Romande, vol. 12, pp. 535, 607. 1892.--Cyon, M. Ueber d.
toxisch. Wirkung. d. Baryt u. Oxalsäureverbindungen. Archiv.
f. Anat., Physiol. u. Wissens. Med., 1866, p. 196.--Mickwitz,
L. Vergleich. Untersuch. ü. d. Physiol. Wirkung d. Salze d.
Alcalien u. Alcal. Erden. Dissert., Dorpat, 1874.--Heilborn,
F. Ueber Veränderungen im Darme nach Vergift. mit Arsen,
Chlorbarium und Phosphor. Dissert., Würzburg, 1891.--Reincke,
J. J. Ein Fall mehrfacher Vergiftung durch kohlensäuren
Baryt. Viertelj. f. gerichtl. Med., n. s., vol. 28, p. 248.
1878.--Orfila, Mémoire sur l'Empoisonnement par les Alcalis
Fixes. Journ. de Chimie Méd., 2 s., vol. 8. p. 200.
1842.--Santi, L. Se nel Veneficio per Sali di Bario questo
Metallo passa alla Urina? Gazz. Chem. Ital., vol. 33, pt. 2,
p. 202. 1903.--Weber, F. R. Barium Chloride. Milwaukee Med.
Journ., vol. 12, pp. 39, 60. 1904.--Rabuteau. De l'Innocuité
des Sels de Strontium Comparée à l'Activité du Chlorure de
Baryum. Gaz. Méd. de Paris, 3 s., vol. 24, p. 218. 1869.--The
very early literature is considered in detail by Bary.
[193] Bary, A. Beitr. z. Baryumwirkung. Dissert., Dorpat,
1888, p. 100.
[194] Onsum, J. Ueber d. toxisch. Wirkung. der Baryt und
Oxalsäureverbindungen. Arch. f. Path. Anat., vol. 28, p. 234.
1863.
[195] Brodie, B. C. Further Experiments and Observations on
the Action of Poisons on the Animal System. Philos. Trans.,
vol. 102, p. 218. 1812.
[196] Tidy, C. M. On Poisoning by Nitrate of Baryta. Med.
Press and Circ., vol. 6, p. 448. 1868.
[197] Glover, R. M. On the Physiological and Medicinal
Properties of Bromine and Its Compounds. Edinb. Med. & Surg.
Journ., vol. 58, p. 341. 1842.
[198] Kissner, G. Ueber Baryum Vergiftungen u. deren Einfluss
auf d. Glykogengehalt der Leber. Scholten, 1896, p. 11.
[199] Mittelstaedt, F. Ueber chronische Bariumvergiftung.
Dissert., Greifswald, 1895, p. 19.
[200] Pelletier, D. Observations sur la Strontiane. Annal. de
Chimie, vol. 21, p. 119. 1797.
[201] Christison, R. Treatise on Poisons. Edinburgh, 1845, p.
579.--Crampe. Bewährte Mittel gegen Feldmäuse. Deutsch.
Landw. Presse, vol. 5, p. 530. 1878.--Felletar, E. Fälle von
Intox. mit kohlensäur. Baryum. Pest. Med.-Chir. Presse, vol.
28, p. 1072. 1892.
[202] Husemann, T. Ein Beitrag z. Kennt. d.
Barytvergiftungen. Zeits. f. pract. Heilk., vol. 3, p. 235.
1866. In this article Husemann has collected many cases of
poisoning by barium in animals.
[203] Christison, R. Treatise on Poisons. Edinburgh, 1845, p.
579.
=BARIUM POISONING IN MAN.=
The high toxicity of barium was called attention to by early observers,
but it was attributed by some to admixed arsenic. The reports of feeding
experiments with barium on animals have varied markedly, but now care is
being advised in the use of barium salts.[204]
Barium was introduced into medicine in the treatment of scrofula, but
has fallen into disuse, and only recently attention has been called to
it on account of its action on the circulatory system. Filippi,[205]
however, says, "The effects on the heart and on the pressure are
already the first indication of poisoning." This metal has also been
used in the treatment of chronic diseases of the spinal cord, as
multiple sclerosis and paralysis agitans.[206]
After the administration to a woman of 1/12 grain (0.005 gram) of barium
chlorid three to five times a day for a few days, a total of 2-1/4
grains (0.135 gram), the patient developed rapid respiration, tenderness
over the epigastrium, nausea, constipation, cramps in the limbs, loss of
appetite, weakness, great emaciation, dysuria, some deafness with
tinnitus, difficulty in speaking and thinking, with vertigo.[207] In
this case the eyes were glassy, the vision indistinct, and the cheeks
flushed. Kohl after the use of small doses of the same noted salivation,
swelling of the gums, and falling out of the teeth, with a mercurial
odor to the breath. Christison[208] states: "I have known violent
vomiting, gripes, and diarrhea produced in like manner by a quantity not
exceeding the usual medicinal doses." According to Kennedy few persons
are able to bear 1/8 grain (0.0075 gram) of barium chlorid.[209]
In Carpenter's case after three doses of 1.6 grains (0.070 gram) of
barium chlorid the patient developed almost lethal symptoms.[210]
Carpenter calls attention to the drowsiness which developed in this
patient after the administration of barium, a fact which had already
been noted by Christison.[211]
A cartarrhal affection of various mucous membranes and a swelling of
various glands have been noted, especially of the lymph and salivary
glands, and in the male the testes have at times swollen.[212] The
inflammation of the glands may pass on to suppuration. The skin becomes
dry and shows a tendency to crack. Febrile attacks are reported after
the repeated use of small doses of barium.
Scheibler[213] has called attention to the possibility of producing
_chronic_ barium poisoning in man from the use of barium in the
manufacture of food products.
Acute cases of poisoning in man from four or more grams of barium
carbonate or chlorid or nitrate have been reported more or less
frequently.[214] In the acute case of poisoning in man reported by
Tiraboschi and Taito, no macroscopic changes were noted in the stomach
mucosa.[215] Lopes[216] has reported one case of acute poisoning in man
from less than 1 gram of barium chlorid. In this case paralysis of the
limbs was a marked feature. Stern[217] cites Perondi and Lisfranc to the
effect that "remarkably large doses of barium chlorid can be borne
without injury by gradually increasing the doses (dissolved in much
water)." Lisfranc[218] has suggested that the sensitiveness to poisoning
by barium salts is greater in certain climates than in others.
No data are as yet available as to the influence of altitude and partial
starvation on the toxicity of barium salts. As is well known, almost
all recorded cases of locoed animals have occurred at a high altitude.