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 Front Cover
 Experiment I
 Experiment II
 Experiment III
 Experiment IV
 Literature cited














Group Title: Bulletin - University of Florida Agricultural Experiment Station ; 611
Title: Urea toxicity in cattle
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 Material Information
Title: Urea toxicity in cattle
Series Title: Bulletin - University of Florida Agricultural Experiment Station ; 611
Physical Description: Book
Language: English
Creator: Davis, George K.
Roberts, Harry F.
Publisher: University of Florida Agricultural Experiment Station
Publication Date: 1959
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Table of Contents
    Front Cover
        Page 1
    Experiment I
        Page 3
        Page 4
        Page 5
        Page 6
        Page 7
        Page 8
    Experiment II
        Page 9
        Page 10
    Experiment III
        Page 11
        Page 12
    Experiment IV
        Page 13
        Page 14
        Page 15
    Literature cited
        Page 16
Full Text


August 1959


UNIVERSITY OF FLORIDA
AGRICULTURAL EXPERIMENT STATIONS
JOSEPH R. BECKENBACH, Director
GAINESVILLE, FLORIDA






Urea Toxicity in Cattle


GEORGE K. DAVIS and HARRY F. ROBERTS
Animal Husbandry and Nutrition Department





Fig. 1.-Positive diagnosis of urea toxicity is made by analyzing blood
samples for urea and for ammonia. Blood drawn from an animal, as shown
here, has a characteristic brownish color.

Nor


Bulletin 611









Urea Toxicity in Cattle


GEORGE K. DAVIS and HARRY F. ROBERTS

For a number of years the attention of Florida Agricultural
Experiment Station workers has been called to situations where
urea has been suspected of causing toxicity in cattle. In most
cases very few animals have been involved and frequently it has
been difficult to be sure that urea caused the animal losses. The
lack of familiarity with urea toxicity symptoms on the part of
cattlemen and veterinarians has resulted in some confusion, and
there has been a need for a clear description of this condition.
The usual cause of urea poisoning has been an error in feed
mixing. In some instances excess urea has been mixed in the
feed, while in other cases poor mixing has resulted in high con-
centrations of urea in some portions of the feed and for this
reason lumps of urea occasionally have caused difficulty.
The experiments, reported here, were carried out to deter-
mine the effects of urea when given to cattle under conditions
which result in the rapid introduction of urea into the rumen.
An effort was made to determine the level of urea which would
cause toxicity when given to a cow in a relatively short period,
such as a single feeding, and also to determine the factors which
might influence this toxic level. These factors included length
of time without feed before the urea was fed, previous adapta-
tion to urea in the diet, and the composition of the feed. In
addition, the production of a condition of urea toxicity in cattle
provided an opportunity to determine changes which occur in
blood urea and blood ammonia values, and to study the effective-
ness of acetic acid as a therapeutic measure.
Since urea is an important ingredient of ruminant feeds, a
knowledge of the factors which limit the amount of urea which
can be fed to cattle safely is especially vital to cattlemen and
to the feed industry.

Experimental Procedure and Results
EXPERIMENT I

The animals in this and following experiments consisted of
Jersey steers raised at the Nutrition Laboratory, dairy cows
from the Dairy Research Unit and animals of mixed breeding
from the Range Cattle Station. Except where noted, cattle






Florida Agricnlturul E.-pe;-inic;: Statiovs


were fed a diet of cracked corn, cottonseed meal, and timothy
hay, and a complete mineral was offered free choice.
Thirteen animals ranging in age from 16 months to mature
cattle were used in this first experiment in an effort to ascertain
the amount of urea which would cause toxicity when given at
a single feeding or when given as a drench.
Three methods of administering the urea were used: drench-
ing, in gelatin capsules, and in the concentrate feed. The cattle
which were drenched with a solution of urea received their
regular morning feed before being drenched. In cases where
urea was fed as part of the concentrate feed mixture, urea in
in the amount shown in Table 1 was mixed with the morning feed.
When the animals were drenched with urea, blood samples
were drawn approximately one hour after feeding and the ani-
mals were then drenched. When urea was in the feed, blood
samples were secured just prior to the feeding. Following urea
administration, blood samples were drawn each 15 minutes for
one hour, or longer if toxicity developed, and at 30 minutes
thereafter until it was certain urea toxicity would not develop.
Twenty grams of urea per 100 pounds live weight per day
was used as a guide since previous reports (3) indicated that this
was about the level at which toxicity might occur in animals
that had not previously had urea. The description of the ani-
mals, method of urea administration, level of urea given and
effect upon the animals are shown in Table 1.
As may be seen in Table 1, 14 grams per 100 pounds (animal
number 1) was fatal when given as a drench. Higher levels
(animals 2 through 6) resulted in toxicity r ;:'irlb -, of the
method of administration, so long as all of the urea was given
at one time. Animals 1, 3, 4 and 5 all died exhibiting character-
istic symptoms of urea toxicity.
When toxicity developed, the animals first showed signs of
uneasiness, then rapid breathing, muscle tremors and slight in-
coordination. These symptoms were followed by severe inco-
ordination, especially in the front legs, excessive salivation and
labored breathing. Eventually the animals lost the ability to
stand and evidence of tetany became increasingly apparent.
Bloat was always present and, unless relieved with a trocar,
appeared to force rumen contents up into the throat with pos-
sible aspiration into the lung. Death occurred 1.5 to 2.5 hours
after the onset of the symptoms, which became manifest 20 to







TABLE 1.-TREATMENT AND RESULTS.


Animal Age
Number

1 30 mo

2 30 mo

3 30 mo

4 18 mo

5 18 mo

6 18 mo

7 Matur

8 Matur

9 Matur

10 16 mo

11 18 mo

12 18 mo

13 17 mo


s.

s.



S.
s.


s.

s.
s._

e

e

e

s.

Is.

Is.

'S.


Sex


M

M

M

M

M

M

F

F

F

_M

F_

F

F


Breed Weight
Lbs.

Jersey 1,025

Jersey 1,155

Jersey 1,030

Jersey 400

Jersey 400

Jersey 400

Jersey 800

Jersey 850

Jersey 850
1/2 Guernsey
1/2 Brahman 610
1/8 Brahman
1/8 Native i 550
1/2 Brahman
S7/16 Shorthorn I 570
1/2 Brahman
1/4 Shorthorn 670


Method
of Dosage

Idrench
given in
gelatin capsules
given in
gelatin capsules

in concentrate


in cone

drench

in cone

in cone

in cone

drench

drench

drench

drench


entrate



entrate

entrate

entrate


Amount of Urea
Gms. Gms./100Lbs.


145

182

227

82

82

90*

0

68

68

95

82

82

82


14.1

15.8

22.0

20.5

20.5

22.5

0

8.0

8.0

15.6

15.0

14.4

12.2


Effects


death after 2 hours 15 minutes

slight ataxia

death, 2 hours 35 minutes

death after 1 hour 40 minutes

death after 1 hour 30 minutes
recovery after treatment wi.h
3,600 ml. 5'; acetic acid

no effect

no apparent effect

no apparent effect

recovery
recovery after treatment with
3,500 ml. 51' acetic acid

death after 2 hours 10 minutes

death after 2 hours 30 minutes


Steer No. 6 received 68 gms. per day initially, the level being increased gradually until an intake of 200 gms. per day was reached. This level
was maintained 42 days, for 7 additional days no urea was given and then a single dors of 90 gms. was administered in water solution.







Florida Agricultural Experiment Stations


30 minutes after feeding. About 30 minutes before death the
labored breathing eased and the tetany relaxed.


Fig. 2-Animals suffering from urea toxicity, such as this Jersey steer,
rapidly develop severe bloat which can be fatal if not relieved.

Animal 6 differed from animals 4 and 5 in that urea in the
concentrate was increased gradually from 68 grams per day to
200 grams per day. At this point, due to an error on the part
of a student assistant, a concentrate feed without urea was sub-
stituted over a week-end. It was decided to keep this animal







Urea Toxicity in Cattle


off urea for seven days, after which it was drenched with 90
grams of urea in water. Toxicity developed rapidly.
Since acetic acid had been proposed as a therapeutic measure
by Repp et al (6), following the observations of Clark et al (1),
a solution of 5 % acetic acid was given orally to animal number 6
as soon as the animal was unable to stand. The amount of
acetic acid given (3,600 ml.) was calculated to be sufficient to
neutralize the ammonia which could be formed from 90 grams
of urea. The recovery was almost as rapid as the development
of the toxicity and appeared to be complete.
Acetic acid therapy was also tried with animals 3, 4, 5, 11,
12 and 13. Administering acetic acid was not effective when
started after the animals went into severe tetany. Prior to this
time, as in animals 6 and 11, response and recovery were rapid.
Animals 7, 8 and 9 became available when called from the
Dairy Research Unit herd and were destined for slaughter. A
level of 8 grams of urea per 100 pounds live weight was chosen.
This is approximately the amount of urea which would be fed

Fig. 3.-About 30 minutes before death from urea toxicity the tetany
relaxes. If 5 percent acetic acid is administered even as late as this, most
animals will recover.







8 Florida Agricultural Experiment Stations












50
0
0

Cm 3
II
LL 40
0



0





Cr















010
0
-J
..J





II






15 30 45 60 75 90 105 120

MINUTES AFTER DOSAGE

Fig. 4.-Effect of administration of water solutions of urea on blood
urea levels in cattle. Animals 1, 3, 10, 11 and 12 received 145, 227, 95, 82
and 82 grams of urea, respectively.







Urea Toxicity in Cattle


in an average feeding of a concentrate feed containing 5%
urea. No signs of toxicity were observed.

BLOOD CHANGES
Blood samples from all the animals in this and subsequent
experiments were analyzed for both urea and ammonia to obtain
an indication of the changes associated with toxicity. The
methods of Van Slyke and Cullen (7) were used.
Results of analyses for urea in blood samples from five ani-
mals are shown in Figure 4. These were chosen as character-
istic of changes which occur in animals which die of urea toxicity
(animals 1, 3, 12), recover without acetic acid therapy (10),
recover with acetic acid therapy (11) and animals which did
not recover following acetic acid administration (3, 12).
Pretreatment blood urea values ranged from 7 to 15 mg. per
100 ml. of blood, while post-treatment values rose to as high as
50 mg. per 100 ml. The high levels of urea in the blood did not
indicate the severity of the toxicity. When severe tetany de-
veloped, the urea levels started to drop but there was no indica-
tion that level of blood urea and degree of tetany were related.
The obvious odor of ammonia on the breath of some of these
animals and the reports of Repp et al (6), Dinning et al (2)
and Clark et al (1) led to the analysis of the blood for ammonia.
Two examples are shown in Figure 5. No animal survived in
which ammonia values of the blood rose above 4.0 mg. per 100
ml. of blood. These values are comparable to those reported
by Dinning et al (2).

EXPERIMENT II

Results obtained accidentally with animal 6 in Experiment
I led to Experiment II in which urea in the feed was increased
gradually to levels much above those which are justified either
nutritionally or economically.
The four cattle used in this experiment were of mixed breed-
ing and a description of the animals and their treatment is
shown in Table 2. Urea was added to a concentrate feed mix-
ture of corn meal and cottonseed meal which was fed twice daily.
Hay and a mineral mixture were offered free choice. The urea
was added to each individual ration and was increased stepwise
from 50 grams per day in increments of approximately 50 grams
every third day. Maximum levels, as indicated, were main-







Florida Agricultural Experiment Stations


trained for one week. At this time urea was eliminated from
the rations for three days for animals 15 and 16 and seven days
for animals 14 and 17. Urea feeding was reinstituted by with-
holding feed at the evening feeding and giving a complete dairy
feed which contained 4% urea the following morning. The
amount of urea consumed by each of the animals is shown in
Table 2.
This feed-to-urea relationship was chosen deliberately since,
while much higher than recommended levels of 3% of the con-
centrate or 1% of the total ration, certain concentrates contain-
ing 4% urea had come to our attention and it was considered
possible that such a level might be fed in practice.





25-

O 23- 5



OO -
O0


00-



Z) Z 9 8



5-
4- .::'::: ::: 5
3-.....%:::::: 4

2-


0-

15 30 45 60 70 90--- 120 180 240
MINUTES AFTER DOSAGE
Fig. 5.-Effect of administration of urea in the concentrate on blood
urea and NH. levels in cattle. Animals 4, 5, 7, 8 and 9 received 82, 82,
0, 68 and 68 grams of urea, respectively.







Urea Toxicity in Cattle


TABLE 2.-EFFECT OF REMOVING UREA FRO\I FEED ON LEVEL OF
UREA TOLERATED.

Highest
Level Renewed Feeding
Animal Age Weight of Urea Gms./ Days of Urea**
Number Months Lbs. Gms. 100 off Causing Toxicity
per Lbs. Urea
Day Gins. Gms./100Lbs.

14 19 600 200 33.3 7 90 15.0
15 17 650 320 49.2 3 120* 18.5
16 18 530 280 52.8 3 114 21.5
17 19 560 400 71.4 7 90 16.1
** Urea was fed as a single feeding of a complete dairy feed containing 41' Urea.
Animal 15 died 3 hours after feeding with symptoms of urea toxicity.

All four of the animals showed some signs of urea toxicity.
These included skin and muscle tremors and slight incoordina-
tion. However, only animal 15 developed severe toxicity. Acetic
acid therapy was initiated too late and this animal died with
characteristic blood changes.

EXPERIMENT III

The effect of feed deprivation on development of urea toxicity
in cattle was studied in Experiment III. Six animals which had
been in either Experiment I or II were maintained for two
weeks to one month on the corn-cottonseed meal-timothy hay
ration without urea. It was considered that any previous adapta-
tion to urea had been lost by this time in view of the results
in Experiment II.
As shown in Table 3, animals 6, 10 and 11 had feed withheld
for 48 hours and animals 14, 16 and 17 were deprived of feed for
24 hours. The animals were given access to water. Three levels
of urea were then used as a drench: 8, 10 and 12 grams per 100
pounds of live weight. Animal number 11, receiving 12 grams
per 100 pounds, showed the most severe reaction but recovered
when given 2 liters of 5% acetic acid as a drench. Animal 6,
receiving 12 grams per 100 pounds of live weight, and animal
17, receiving 12 grams per 100 pounds, showed slight signs of
toxicity and No. 17 was given acetic acid.
Results of this experiment suggest that animals which have
gone without feed for one or two days are more susceptible to
urea toxicity than animals on feed.

















TABLE 3.-EFFECT OF STARVATION ON UREA TOLERANCE.


Weight Feed Removed *Urea Feeding
Age Pounds for-Hours Gms. Gms./100Lbs. Reaction


17 680 48 56 8.2 none

19 480 48 50 10.4 slight tremors

19 605 48 72 11.9 toxic reaction


14 20 620 24

16 19 540 24

17 20 590 24
* Urea was given as a weighed amount in a drench.
** Acetic acid was given as a 51c solution as a drench.


none

none
slight inco-
ordination


**Treatment


none

none

2,000 ml. acetic acid

none

none

2,000 ml. acetic acid


Animal
Number


10

6

11


Result




recovery

recovery





recovery







Urea Toxicity in Cattle


EXPERIMENT IV

Work reported by Clark et al (1) indicated that, in sheep,
low-protein roughages may increase susceptibility to urea tox-
icity. In Experiment IV three animals were given timothy hay
which analyzed 4.1 percent protein and no concentrate feed
and three animals were kept on the corn-cottonseed meal-hay
ration which provided 10.2 percent protein. After 10 days on
the rations all the animals were given 50 grams of urea in corn
meal at a single feeding.
Allotment of the animals and results obtained in Experi-
ment IV are shown in Table 4. The three animals on timothy
hay alone showed some skin and muscle tremors with a slight
ataxia lasting up to two hours but all recovered without further
evidence of toxicity. There was no indication of toxicity in
the cattle given the concentrate feed.

TABLE 4.-EFFECT OF PROTEIN LEVEL ON UREA TOXICITY.


Ani- Age Wt.
mal Mos. Lbs.


Crude
Protein
Feed ILevel
S/Dry
Weight


Level of Urea*
Re-
Gms. Gms./100Lbs. action


24 18 580 timothy hay


25


19


590 timothy hay


26 18 610 timothy hay
concentrate
and
27 19 550 timothy hay
concentrate
and
28 20 605 timothy hay
S concentrate
I and
29 18 585 timothy hay


slight
4.1 50 8.6 ataxia
slight
4.1 50 8.5 ataxia

slight
4.1 50 8.2 ataxia


10.2 50 9.1 none


10.2 50 8.3 none

10.2 50 8.5 none


Urea given as a single feed mixed in corn meal.

Discussion

Results of these experiments indicate clearly that urea will
cause a toxic condition in cattle when it is fed in excess amounts
over a short period, or given as a drench to animals which have
not become adapted to urea in the feed.






Florida Agricultural Experiment Stations


In Experiment I it was evident that a single feed or drench
of 14 to 20 grams of urea per 100 pounds of live weight would
precipitate an acute toxicity. Experiment II demonstrated that
levels much in excess of those used in Experiment I could be
incorporated into feeds safely, if the level was increased grad-
ually. These high levels are not recommended, since they are
poorly utilized.
Also, it was shown in Experiment II that adaptation to high
levels of urea is rapidly lost when urea is removed from the
diet, and care should be exercised when urea is reincorporated
into a diet after a period of no urea feeding.
Experiment III indicates that relatively short periods with-
out feed decrease the amount of urea which can be safely fed
at one time. Probably not more than 8 grams of urea per 100
pounds live weight should be fed at a single feeding to animals
which have gone without feed for 48 hours.
Experiment IV emphasizes the value of concentrate feeds
in preventing toxicity. Animals which have been kept on low
quality roughages for any length of time should be given only
low levels of urea until they have had time to adapt to this
material.
The common practice of feeding urea in molasses was not
investigated in these trials. Gallup et al. (3) in Oklahoma
found that toxicity did not develop in cattle fed cane molasses-
urea mixtures in 6:1 and 5:1 ratios. They found that in cattle
starved for two days, 20 grams of urea in molasses per 100
pounds of live weight were necessary to produce toxicity in
animals which had not received urea previously.
Both cane molasses and citrus molasses containing 60 to 80
pounds of urea per ton have been used successfully in free choice
feeding of cattle in Florida. Steers at the Range Cattle Station
on native range which were given citrus molasses containing
3 percent urea, free choice, ate an average of 14.49 pounds daily
per animal (197 grams urea) without any ill effect during a
120-day feeding trial (5).
In some instances in Florida urea toxicity has developed
in cattle consuming excessive amounts of urea-molasses mix-
tures at a single feeding. Ordinarily consumption is limited
by the physical character of molasses. When cane molasses is
diluted with water either intentionally, for ease of mixing, or
accidentally, because of heavy rainfall, and offered to cattle, the
animal may consume large quantities. The senior author has






Urea Toxicity in Cattle


observed instances of cattle consuming from 12 to 16 pounds
per head at a single feeding. With such a high intake of mo-
lasses containing 3 or 4 percent urea, toxicity may result.
Under such circumstances the cattle have exhibited a tem-
porary blindness, followed by the usual signs of toxicity unless
they are given feeds without urea or treated with acetic acid
as a therapeutic measure. Since these were field observations,
it is not certain that the blindness resulted from the urea.
Acetic acid when used early in the development of urea tox-
icity has been very effective in preventing losses. Clark et al.
(1), working with fistulated sheep, observed that high intakes
of urea resulted in the release of ammonia with a rapid increase
in the pH of the rumen contents. They demonstrated that
alkalis decreased urea tolerance and acetic acid increased urea
tolerance. Repp et al. (6) in Iowa noted that acetic acid given
either intravenously or orally increased urea tolerance. When
administered before the onset of tetany, it was a good thera-
peutic measure.
Hale and King (4) at Iowa State College proposed that the
toxic action of urea probably was not due to the absorption of
either urea or ammonia, but to the absorption of ammonium
carbamate formed by combination of ammonia and carbon di-
oxide in the rumen. They suggested that the acetic acid broke
down the ammonium carbamate. Neutralization of ammonia
would occur also.
In the work reported here, acetic acid was effective if given
orally before tetany became severe. Good results were obtained
with a 5% acetic acid solution in an amount sufficient to neu-
tralize the ammonia which could be produced from the urea fed.
However, under practical farm conditions, approximately one
gallon of common vinegar given orally is an easily available
material for therapy.

Conclusions and Recommendations
Urea toxicity did not develop in cattle when urea was fed
at levels comparable to 1'c of the total ration or 3% of the
concentrate.
Cattle will develop a tolerance for urea when the daily intake
is increased gradually.
No feed intake for 24 to 48 hours appears to decrease toler-
ance for urea.
Low protein diets may result in a lower tolerance for urea.






Florida Agricultural Experiment Stations


Adaptation to even high levels of urea is lost rapidly. Ani-
mals which have been without urea for as long as three days
should be given only low levels until readapted to higher intakes.
Urea toxicity develops rapidly. The symptoms include un-
easiness, muscle and skin tremors, excess salivation, labored
breathing, incoordination or ataxia, bloat, tetany and death.
None of the animals in which blood ammonia values exceeded
4.0 mg per 100 ml. of blood survived.
Acetic acid as a 57o solution or as vinegar is an effective
cure in many cases of urea toxicity if given before the develop-
ment of severe tetany.


Literature Cited

1. CLARK, R., W. OYAERT and J. I. QUIN. The toxicity of urea to sheep
under different conditions. Onderstepoort Jour. Vet. Res. 25: 73-78.
1951.
2. DINNING, J. S., H. M. BRIGGS, W. D. GALLUP, H. W. ORR and R. BUTLER.
Effect of orally administered urea on the ammonia and urea con-
centration in blood of cattle and sheep with observations on blood
ammonia levels associated with symptoms of alkalosis. Am. Jour.
Physiol. 153: 41-46. 1948.
3. GALLUP, W. D., L. S. POPE and C. K. WHITEHAIR. Urea in rations for
cattle and sheep. Okla. Agri. Exp. Sta. Bul. B-409. 1953.
4. HALE, W. H., and R. P. KING. Possible mechanism of urea toxicity in
ruminants. Proc. Soc. Exptl. Biol. and Med. 89: 112-114. 1955.
5. KIRK, W. G. Unpublished data. Range Cattle Station, Ona, Florida.
6. REPP, WARD W., W. H. HALE, E. W. CHENG and WISE BURROUGHS. In-
fluence of oral administration of non-protein nitrogen feeding com-
pound upon blood ammonia and urea levels in lambs. Jour. Am. Sci.
14: 118-131. 1955.
7. VAN SLYKE, D. D., and G. E. CULLEN. A permanent preparation of
urease and its use in the determination of urea. Jour. Biol. Chem.
19: 211-228. 1914.


Acknowledgments

The authors wish to express their gratitude to Jason C. Outler for help
in treatment and feeding of the animals, to Dr. J. T. McCall for assistance
in analysis of blood and feed, to Dr. W. G. Kirk for supplying the animals
obtained from the Range Cattle Station, to Dr. R. B. Becker for supplying
animals from the Dairy Research Unit, to R. E. Burke of E. I. duPont
de Nemours and Co., who supplied the urea, and to Dr. Charles F. Simpson
for post mortem observations on the cattle.




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