M. F. Raisbeck DVM, Ph.D., DABVT ~ S. L. Riker, B.S. ~ C. M. Tate, D.V.M., Ph.D.

R. Jackson, Ph.D. ~ M. A. Smith, Ph.D. ~ K. J. Reddy, Ph.D. ~ J. R. Zygmunt, B.S.

Water Quality

for Wyoming Livestock & Wildlife

A Review of the Literature Pertaining to Health Effects of Inorganic Contaminants

University of Wyoming Department of Veterinary Sciences, 

UW Department of Renewable Resources, 

Wyoming Game and Fish Department, 

Wyoming Department of Environmental Quality

B-1183
Acknowledgements

The authors would like to thank the Wyoming Department of Environmental Quality for providing the funding 

needed to complete the report and Louise Smithson and Rebecca Dailey from the Wyoming State Veterinary Laboratory and Robert Waggener, editor in the UW College of Agriculture, for the many hours they invested in editing. We 

thank Bernadette van der Vliet, graphic designer in the College of Agriculture, for her work on layout and design. We 

would also like to acknowledge the following colleagues who reviewed the report and offered constructive criticism 

and suggestions.

Michelle Mostrom, D.V.M., M.S., Ph.D., DABVT

Veterinary Toxicologist, North Dakota State University

John C. Reagor, M.S., Ph.D.

Head, Diagnostic Toxicology, Texas Veterinary Medical Diagnostic Laboratory, Texas A&M University

Michael Carlson, M.S., Ph.D.

Toxicology Analytical Chemist and Lecturer, University of Nebraska-Lincoln

Patricia Talcott, D.V.M., Ph.D., DABVT

Associate Professor of Veterinary Toxicology, Washington State University

ii
iii

Abbreviations

ADG – average daily gain

As – arsenic 

Ba – barium 

BW – body weight

C – Celsius

CNS – central nervous system

Cp – ceruloplasmin

Cu – copper 

DM – dry matter

DMA – dimethylarsonous acid

DMI – dry matter intake

ECF – extracellular fluid

ECG – electrocardiogram

EPA – U.S. Environmental Protection Agency

EU – European Union

F – Fahrenheit

F – fluorine 

FDA – U.S. Food and Drug Administration

g – gram

G.I. tract – gastrointestinal tract

GSH – glutathione

Hb – hemoglobin

HDL – high-density lipoprotein 

Hg – mercury

H2S – hydrogen sulfide

IV – intravenous

kg – kilogram

L – liter

lb – pound

LD50 – Dose which is lethal in 50% of the tested 

population

LD0 – Largest non-lethal dose in tested population 

(theoretical)

meq – milliequivalent

MetHb – methemoglobin

mg – milligram

mM – millimole

MMA – monomethylarsonous acid

Mo – molybdenum 

MT – metallothionein

N – nitrogen 

Na – sodium 

nAChR – nicotinic acetylcholine receptor

NaCl – sodium chloride

NOAEL – no observed adverse effect level

NO3

- – nitrate

NO2

- 

– nitriteNRC – National Research Council

PEM – polioencephalomalacia

ppm – parts per million

ppb – parts per billion

% – percent 

ROS – reactive oxygen species

S – sulfur 

Se – selenium 

SOLD50 – single oral median lethal dose

T1/2 – biological half-life

TCA – trichloroacetic acid

TDS – total dissolved solids 

TM – thiomolybdates

USDA – U.S. Department of Agriculture

WSVL – Wyoming State Veterinary Laboratory
iv
v

Contents

Acknowledgements ii

Abbreviations iii

Contents V

1 Introduction1

2 Arsenic5

Essentiality  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  . 5

Metabolism 5

Toxicity 6

Summary 8

3 Barium11

Essentiality  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .11

Metabolism 11

Toxicity 11

Summary 13

4 Fluoride15

Essentiality  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .15

Metabolism 15

Toxicity 15

Summary 18

5 Molybdenum21

Essentiality  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .21

Metabolism 21

Toxicity 22

Summary 24

6 Nitrate and Nitrite25

Essentiality  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .25

Metabolism 25

Toxicity 25

Summary 28
vi

7 pH 31

Function. . . . . . . . . . . . . . . . . . . . . . . . . . . . .31

Metabolism 31

Toxicity 31

Summary 32

8 Selenium 35

Essentiality . . . . . . . . . . . . . . . . . . . . . . . . . . .35

Metabolism 35

Toxicity 36

Summary 38

9 Sodium Chloride 41

Essentiality . . . . . . . . . . . . . . . . . . . . . . . . . . .41

Metabolism 41

Toxicity 41

Summary 43

10 Sulfur 45

Essentiality . . . . . . . . . . . . . . . . . . . . . . . . . . .45

Metabolism 45

Toxicity 46

Summary 47

11 Total Dissolved Solids (TDS) 49

Essentiality . . . . . . . . . . . . . . . . . . . . . . . . . . .49

Metabolism 49

Toxicity 49

Summary 50

12 Summary 51

13 Research Needs 53

14 Bibliography 55
 1

1 Introduction

Water is the single most important nutrient for livestock 

and big game wildlife species. It is the most abundant 

ingredient of the animal body in all phases of growth and 

development. A calf’s body contains 75 to 80% water 

at birth and about 55 to 65% water at maturity. While 

animals can survive for a week or more without food, 

death is likely in a matter of days without adequate water 

intake. Water is involved either directly or indirectly 

in virtually every physiologic process essential to life. 

Water is the medium in which all chemical reactions in 

the body take place. Blood, which contains 80% water, 

is vital in transporting oxygen to the tissues and carbon 

dioxide from the tissues as well as being the life support 

system for the body. It is the medium for transporting 

nutrients, metabolic wastes, and chemical messengers, 

such as hormones, throughout the body. It provides the 

chemical base for nutrient digestion and uptake from the 

GI tract and for the elimination of waste products via 

urine and bile. Water’s physical properties make it an 

important factor in the transfer of heat and the regulation of temperature in the body. Due to its high specific 

heat (the ability to absorb or give off heat with a relatively 

small change in temperature), water is ideally suited as a 

temperature buffering system for the body. A restriction 

of water intake lowers feed intake and N retention (i.e. 

protein), and it increases N loss in the feces. It also results in increased excretion of urea in the urine. Animals 

may survive a loss of nearly all the fat and about one-half 

of bodily protein, but a loss of about one-tenth of water 

from the body results in death.

Obviously, an adequate supply of clean water is necessary to the health of all animals, including human beings. 

Under most management systems, water is the cheapest 

and most readily available nutrient. Unfortunately, and 

probably because of this fact, it is also the most overlooked nutrient. Sources of water include those obtained 

from wells or surface runoff, water contained in feedstuffs 

(lush grass may consist of as much as 75% water) and 

metabolic water obtained from the oxidation of fat and 

protein in the body. In the arid western United States, 

good quality water is a scarce commodity, and livestock 

and wildlife are often forced to survive on what might 

be charitably described as “less-than-perfect” water due 

to competition from urbanization, mineral extraction, 

etc. In most cases, these animals do surprisingly well, but 

poor quality water has resulted in acute illness and death. 

It also robs producers via decreased performance (growth, 

reproduction). Thus, awareness of water quality issues 

has increased as the competition for resources intensifies. 

Ranchers, wildlife managers, conservationists, veterinarians, cooperative extension personnel, animal owners, and 

others need to know whether a particular source of water 

is safe. One of the more common questions fielded by 

our laboratories is “what is X ppm of Y in the water going 

to do to my cattle (horses, deer, etc.)?” 

Water consumption is influenced by many factors, including genetics (species, breed), age, body size, ambient 

temperature and humidity, water temperature, and level 

of production. For example, cattle (a species that has 

been studied extensively) consume an average of 2 to 4 

kg of water for each kg of dry matter consumed and an 

additional 3 to 5 kg of water per kg of milk produced; 

however, this average varies dramatically with temperature, especially when the environmental temperature 

exceeds the thermo-neutral range (5-20 C in cattle) making animals lose increasing amounts of water via respiration and sweating. For example, a 273-kg (600 lb) feeder 

steer drinks 22.7 L at 5 C or below; at 21 C (70 F), he 

needs 33 L but at 30 C (roughly 86 F) he requires 54 L 

or 20% of his body weight per day.1 At 39 C (roughly 

102 F), he would require 116 L.2 Rations high in Na, 

fiber, or protein also increase water requirements.1,3 For 

example, horses consume twice as much water while on a 

hay diet compared to a high concentrate diet at the same 

temperature.4 The level of production is a very important 

factor in water requirements. A lactating beef cow requires nearly twice as much water (64 L or about 16% of 

her body weight) per day at 21 C as the same cow (32.9 

L, 9% body weight) when dry (not lactating) at the same 

temperature, and a high-producing dairy cow of similar 

size needs 90 L, or nearly 20% of her body weight under 

the same conditions.1,5 At 32 C, she may drink as much 

as 40% of her body weight.1,6 

The amount (dose) of any water-borne toxicant ingested 

by a given animal is determined by the concentration of 

the substance in water and by the amount of water the 
2

animal drinks. Water intake is technically defined as freedrinking water plus the amount contained in feedstuffs; 

however, for purposes of simplicity in this report, we 

have assumed animals are consuming air-dried hay or 

senescent forage with a minimal (10%) water content 

and will use the term “intake” to describe the amount 

of water consumed voluntarily by animals from streams, 

ponds, etc. The amount an animal drinks is determined 

by true thirst and appetite. By definition, true thirst is 

the physiologic drive to consume sufficient water to meet 

minimum metabolic needs; however, most animals also 

exhibit an “appetite” for water and consume more than is 

strictly necessarily to satisfy thirst.7 Reasons for the latter 

are many, varied, and do not lend themselves to quantitative prediction. We therefore disregarded appetite in 

calculating doses from water intake but instead used fairly 

conservative estimates of thirst in such calculations by 

disregarding forage water content. Most calculations of 

potential toxic doses in this report are thus based upon 

273 kg (600 lb) feeder cattle that drink approximately 

20% of their body weight, or about 8 L per kg of dietary 

dry matter, per day, at 32 C (90 F). This may not provide 

adequate protection for high-producing dairy cattle, 

which drink significantly more under similar environmental conditions, but is reasonably conservative for 

range livestock (beef and sheep) and weather conditions 

typical of Wyoming. Higher temperatures would also result in higher consumption than our “standard” steer, but 

sustained periods of such weather are not that common 

in Wyoming.8 Finally, there is virtually no information on 

water consumption by the major wildlife species covered 

in this report, but it is reasonable to assume that species 

that evolved in the northern Great Plains would not have 

greater requirements than domestic cattle.

This report is targeted at domestic livestock and wildlife (beef cattle, horses, sheep, deer, elk, and pronghorn 

antelope) that rely upon wells, ponds, streams, and other 

water sources on Wyoming’s ranges. Although we have 

made note of data related to swine where we found them, 

virtually all modern swine are raised in intensive operations that draw water from systems (municipal, water 

district, etc.) that are maintained according to human 

drinking water standards. Similarly, “alternative agricultural” species such as llamas and bison are not included, 

in part because of a scarcity of data.

Water quality is commonly evaluated by chemical 

methods that have been designed to be very reproducible 

and very specific. As a result, the process of analyzing 

water is fairly straightforward, and many tests are readily 

available, commercially. Unfortunately, translating these 

very precise, formal, data to practical recommendations 

for livestock and wildlife is less cut and dried. As noted 

by Dr. Art Case, the dean of veterinary toxicologists, 

“sometimes the cow just didn’t read the book.” First, 

many toxicants in water act additively with the same 

toxicant in feedstuffs. In most such cases, the bottom 

line is not necessarily the water concentration but rather 

the total mg of toxicant ingested per kg of the animal’s 

body weight (commonly expressed as “mg X/kg BW”). 

Throughout this report, we have tried to use realistic estimates of total dietary concentrations of such toxicants to 

calculate the water concentration of the toxicant required 

to potentially cause problems. 

Second, chemical water quality tests do not usually 

measure the specific chemical form of the toxicant present. For example, Se as selenite or selenate behaves quite 

differently in the mammalian body than does selenomethionine, but the typical laboratory just reports total Se. 

Where possible, we have based recommendations upon 

the chemical form most likely to be present in typical 

surface waters in Wyoming and noted any caveats that 

should be considered if the water source is not “typical”. 

In the absence of other data, we have assumed the free 

ion in water is equivalent on a mg/kg BW basis to the 

same chemical in feedstuffs. 

Third, typical chemical tests do not differentiate between 

animal species. Some substances are more toxic in ruminants than monogastrics (simple-stomached animals) as 

a result of their unique physiology; some are less. While 

we have tried to identify significant differences where 

they exist, our recommendations are based upon the 

most sensitive of our species of interest. 

Fourth, many toxic substances interact with other 

toxicants and/or nutrients in the diet. We have tried to 

enumerate such interactions in the narrative if they are 

well documented and, where possible, account for them 

in the “bottom line” calculations of acceptable water 

concentrations. 

Finally, the rate of exposure influences the potency of 

many toxicants. A bolus dose of nitrate (NO3), given 

via a stomach tube, is much more toxic than the same 

amount spread over an entire day’s grazing. Under 

summer range conditions typical of the Great Plains, 

livestock drink once, or, at most, twice a day. Wildlife 

typically trek to water and drink their fill during the 

morning and evening twilight. We have, therefore, 

assumed all of the water-borne daily dose of a given 
3

substance will be consumed during a fairly short period, 

once or twice a day. 

Water quality constituents in this report were drawn from 

common water quality guidelines, prioritized according to how closely, in our experience, existing Wyoming 

concentrations approached these guidelines and how 

often the elements in question caused poisoning in 

Wyoming animals. For example, Hg is much more toxic 

than many of the elements we studied, but it is rarely 

present at detectable concentrations in Wyoming water 

surveys. Copper is a real problem in aquatic organisms, 

but Cu deficiency is a much bigger problem in livestock 

than Cu toxicity. We then worked our way as far down 

this prioritized list as time permitted. Obviously, there 

are more constituents on our list than we were able to 

examine, but we believe we covered those most important 

to Wyoming.

Data used in compiling this report are drawn primarily from scientific literature, including refereed journals, 

texts, proceedings, abstracts, and theses, with an emphasis 

on material published during the last 20 years. The basic 

strategy consisted of 1) searching biomedical databases 

(e.g. Medline, CAB Abstracts, etc.) for reports of toxicity 

in any species, 2) examining bibliographies of relevant 

papers for new leads, and, finally 3) forward searching 

(e.g. Science Citation Index) for more recent papers that 

cite earlier work on a given topic. We also solicited welldocumented anecdotal data (i.e. field reports) from colleagues at other research and/or diagnostic institutions. 

Where possible, we tried to validate secondary sources 

(e.g. reviews, texts) by examining primary documents 

from which they were drawn. If sufficient data existed for 

our principle species of interest (beef cattle, horses, sheep, 

elk, deer, and antelope) we focused on those reports. If 

not, we attempted to extrapolate from rodents, humans, 

etc., being careful to identify the uncertainty factors inherent in such extrapolations. Each source was assigned 

a rating for reliability, with peer-reviewed, experimental 

studies usually, but not always, being considered more 

reliable. 

As noted previously, the interaction of water quality and 

animal health is considerably more complex than just 

“X” mg of “Y” per L of water. For example, many factors 

have been suggested to influence the palatability of water 

for animals. Decreased consumption due to bad taste 

is potentially just as harmful as water deprivation3, yet 

the state of the art regarding palatability is still largely 

qualitative and anecdotal. Acid pH may mobilize toxic 

metals from plumbing or soil, but the particular effect 

of a given pH is obviously very dependent on the local 

situation. A sudden transition to pure water after several 

weeks on highly saline water may result in so-called “salt 

poisoning.” Where adequate, quantitative data exists for 

non-directly toxic adverse effects on health, we have incorporated them into the final recommendations. Where 

there is substantial evidence suggesting such effects exist, 

but no reproducible, quantitative data were available, we 

tried to mention the existence of such effects but have not 

factored them into the final recommendations.

Safety margins are a matter of judgment rather than 

an exact science. The purpose of safety margins is to 

compensate for unknown, or unknowable, variables in 

toxicology data such as genetic variability, sex, life stage, 

duration of exposure, unforeseen interactions with other 

toxicants, etc. The standard practice in setting human 

drinking water standards for non-carcinogens has been to 

divide the geometric mean of the NOAEL and minimum 

toxic dose by 10 to 1,000 depending upon whether 

the data are derived from human exposure, multiple 

non-human species, or incomplete data in any species. 

Another approach used in the past has been to set the safe 

limit at the upper end of the range commonly reported 

in natural waters as was done with Se.2 Both approaches, 

while unarguably “safe,” ignore the realities of livestock 

production in the western United States. Water that is so 

“perfect” as to meet these theoretically desirable criteria 

has already been taken for other uses. In this report we 

have taken the approach of presenting our best estimate 

of the NOAEL (i.e. will not produce any measurable 

decrease in performance in the most sensitive class of 

animal) under a very conservative set of assumptions 

appropriate to Wyoming and allowing readers to make 

their own judgment regarding “safety” margins.

The final report, together with the documents it was 

drawn from, was forwarded to colleagues at four other 

universities (Washington State University, University 

of Nebraska, North Dakota State University, and Texas 

A&M University) for peer review. Their comments were 

considered and incorporated into the final document.

Although there are many ways of expressing measurements regarding water quality and toxicology, we have 

chosen to use the following conventions. The dose of a 

toxicant that causes some particular effect is expressed in 

milligrams of substance per kilogram of body weight or 

“mg X/kg BW”. The concentration of a substance in water is expressed as milligrams of substance per liter of wa-
4

ter or “mg X/L”. If the substance is ionized, and the ion 

is important in terms of toxic effects, it will be described 

with the standard scientific abbreviation for the ion, e.g. 

“NO3

-

”. Similarly the concentration of a toxicant occurring in dry feedstuffs will be described in terms of parts 

per million or ppm. Single elements are abbreviated with 

the standard chemical symbol (e.g. “Se” for selenium).

This report, and the project that created it, was funded 

by the Wyoming Department of Environmental Quality. 

Although the authors anticipate they will find the information useful, our intended audience is much broader 

and includes ranchers, wildlife managers, conservationists, veterinarians, cooperative extension personnel, animal owners, and others. The last concerted effort in the 

United States to summarize the literature regarding water 

quality for animals occurred more than 30 years ago2, 

and there have been many additions to the knowledge 

base since that time. We believe this report represents a 

reasonable starting point for evaluating the adequacy of 

water quality for animals.
5

Arsenic (As) is a metalloid that occurs naturally in water 

and soil. It is also released from a number of human 

activities including mining, petroleum and natural gas 

extraction, wood preservation, and burning coal.9-16 

Although As is rare in nature as a pure element, both inorganic and organic forms of As are commonly found in 

a number of different oxidation states, of which two (+3 

and +5) occur in soil, water, and vegetation. Inorganic 

forms of AsIII (e.g. the arsenite ion) may be found under 

reducing conditions; however, AsV (e.g. the arsenate ion) 

predominates in surface waters containing considerable 

dissolved oxygen.17 Organic arsenical compounds have 

also been used as herbicides, insecticides, and drugs. 

Arsenic was one of the first drugs to be used successfully 

against the syphilis organism in humans. The organic 

arsenical roxarsone (4-hydroxy-3-nitrobenzenearsonic 

acid) is still used to control coccidia in poultry and swine. 

More recently, arsenic trioxide (As2O3) has been suggested for treatment of promyelocytic leukemia and multiple 

myeloma.18

Most of what was known about the toxicity of As prior 

to the 1980s was based upon the direct cytotoxic effects 

of As.19 More recently, however, chronic consumption of low-level As-contaminated drinking water has 

become associated with a variety of chronic maladies in 

human beings, including cardiovascular disease, “blackfoot disease,” diabetes mellitus, spontaneous abortion, 

and, especially, cancer.9,20-22 Conversely, some reports23,24

suggest a hormetic (beneficial) effect of As at very low 

doses. So far the majority of the evidence for chronic 

effects in humans consists of epidemiological studies, but 

mechanistic, toxicologic explanations are appearing in the 

literature. The latter are important because they suggest 

these effects (and therefore dosages) are not likely relevant 

to our species of interest (see below for details). 

The nomenclature of the arsenicals is often bewildering. In this text, the following conventions are used: the 

trivalent, methylated metabolites (mono)methylarsonous 

acid, and dimethylarsonous acid will be abbreviated as 

MMAIII and DMAIII, the pentavalent metabolites (mono)

methylarsonic acid, and dimethylarsinic acid as MMAV

and DMAV, and the inorganic ions such as arsenite and 

arsenate as iAsIII and iAsV.

Essentiality

Although the physiological function(s) of As remains 

unknown, experiments with As deprivation in many 

species suggest As may be an essential element.25 For 

example, rats maintained on a diet containing 30 ppb As 

exhibited decreased growth rate, rough hair coats, and 

decreased hematocrit levels when compared to controls supplemented with 4.5 ppm As.26 Lactating goats 

consuming a diet containing less than 10 ppb As had 

decreased growth rates, decreased milk production, lower 

birth weights, and a higher incidence of mortality.27 

Female miniature pigs on a low As diet produced smaller 

piglets, and only 62% of pigs were reported to give birth 

when compared to pigs supplemented with 350 ppb 

As.27 The results of experimentally induced deprivation 

in both in vivo and in vitro experiments suggest As plays 

a role in the methylation of both proteins and genetic 

molecules.25 Although this and other, similar research 

is scientifically interesting, As deficiency has never been 

demonstrated in nature, probably because the apparent 

nutritional requirements are considerably lower than 

common background concentrations.

Metabolism

It is commonly accepted that, with the possible exception of the trivalent methylated metabolites (MMAIII

and DMAIII), the inorganic forms of As are considerably 

more toxic in mammals than organic arsenicals.20,25,28-30 

Since the inorganic forms are also by far the most common contaminants of water under field conditions and 

because MMAIII and DMAIII are too unstable to persist 

for any length of time under natural conditions, this 

review will focus upon exposure to the inorganic forms 

of AsIII and AsV. Arsenate is absorbed from the gut by a 

two-stage process. First, it is concentrated in mucosal 

cells then, as binding sites become filled, it moves down 

the resulting concentration gradient into the portal 

circulation.25 The absorption mechanism of iAsIII is less 

completely understood, but it is commonly accepted that 

iAsIII is even more readily absorbed than iAsV, probably 

because of its greater water solubility.17 Once absorbed, 

As is transported to various tissues via blood. Distribu2 Arsenic
6

tion between the erythrocytic and plasma components 

of blood depends upon the dose of As given, the species of animal, and the valence of administered As. In 

general plasma concentrations increase relative to red cell 

concentrations as the dose increases, and trivalent As has 

a higher affinity for erythrocytes than AsV, resulting in 

slower clearance. Humans, rats, and mice have higher 

erythrocyte binding than other domestic mammals, also 

resulting in slower elimination.17,27

The metabolism and excretion of As varies significantly 

between species and between genotypes within the 

human species.27,31-33 These species-specific differences 

in metabolism are important in the pathogenesis of As 

intoxication in any given species.17,27 Generally speaking, inorganic As is methylated in vivo via a series of 

sequential reduction and oxidative-methylation reactions. Inorganic AsV is reduced in a linked reaction 

with oxidation of reduced glutathione (GSH) to iAsIII, 

which is then methylated to MMAV by reaction with Sadenysylmethionine. Monomethylarsonic acid (MMAV) 

is, in turn, reduced and methylated to DMAV and so 

forth.22 These metabolites are more readily excreted than 

inorganic As. In many, but not all, mammalian species, 

this process proceeds to DMAV or the trimethyl arsenic 

metabolite trimethylarsine oxide (TMAO); however, 

in human beings, significant amounts of MMAIII and 

DMAIII apparently escape methylation and react with 

critical tissue components. The rate of methylation and 

physiologic site of metabolism are thus important determinants of the rate of elimination and the potential for 

chronic effects at very low doses.22,29

As interacts with many other dietary factors, resulting 

in either increased or decreased toxicity. As has been 

known to minimize the toxicity of Se for many years.34-37

When As is fed with Se, the excretion of both elements 

in feces is enhanced.37,38 Simultaneous administration 

of Zn lessened the toxicity of As-spiked drinking water, 

possibly by induction of metallothionein, a metal binding 

protein.22,39 Folate can affect As methylation and both 

folate deficiency and excess As induce fetal malformations 

in rats, thus a dietary deficiency of folate potentiates As 

toxicity.22,40

Toxicity

The acute toxicity of inorganic As has been attributed 

to the generation of reactive oxygen species (ROS) and 

oxidative stress18,21,39, to the denaturation of critical protein moieties, and to interfering with phosphate metabolism.17,41 In virtually all models, iAsIII is reported to be 

several fold more toxic than iAsV.

28,30,41,42 Trivalent iAsIII

exerts its toxic effects by binding with specific functional 

groups (thiols and vicinyl sulfhydryls) on enzymes, receptor proteins, etc.10,17,27,43 For example, mitochondrial 

respiration is blocked by the reaction between AsIII and 

the dihydrolipoic acid cofactor required for substrate 

oxidation.41 As cited by Thomas et al.44, in 1966 Webb 

listed more than 100 enzymes that were inhibited by 

AsIII. Pentavalent AsV, because of its chemical similarity 

with the phosphate ion, displaces phosphate from certain 

biochemical reactions, e.g. oxidative phosphorylation, 

resulting in depletion of ATP10,41,43-45, but it may also be 

converted to AsIII in vivo (i.e. in tissues) and in the rumen.45 The clinical signs associated with acute toxicity in 

virtually all species include diarrhea, vomiting, abdominal 

pain, weakness, staggering gait, myocardial degeneration, 

and, in some cases, death.17,25,30,43,45 

Most acute As toxicity results from accidental exposure 

as a result of improper handling, use, and/or storage of 

arsenical compounds.13,15,45 Cattle began staggering and 

showing signs of abdominal pain, diarrhea, anorexia, and 

recumbency shortly after ingesting forage that had been 

sprayed with sodium arsenite (NaAsO2). Analysis of the 

grass performed several days later revealed it contained 2 

ppm As, but the author noted concentrations were probably higher immediately after spraying.46 Cows and calves 

became recumbent and exhibited a rapid weak pulse, 

intermittent clonic convulsions, and paddling movements 

after drinking fluid from a dipping vat containing 200 

mg As/L.47 A herd of approximately 275 cattle allowed 

to graze a road right of way recently sprayed with sodium arsenate (Na2

HAsO4) sickened within hours, and 

80 died within four days. Samples of grass taken at the 

onset contained 10,500 ppm As.14 Selby et al. reported a 

similar scenario in Missouri in which the toxic vegetation 

contained 440 ppm As.48 Cattle that consumed water 

containing 6-20 mg As/L and silage contaminated with 

140 ppm As became progressively weaker, emaciated, and 

recumbent, had decreased milk production, and eventually died after several days.49 Nine adult cattle developed 

acute hemorrhagic diarrhea, and two eventually died 

after consuming a dairy premix containing 5.50 ppm As; 

however, the As concentration of G.I. contents suggests 

the exposure may have been considerably higher.50 Heifers became weak, recumbent, dysenteric, and died after 

ingesting vegetation containing approximately 2,000 

ppm As from herbicide contamination.51 Approximately 

12 hours after consuming pellets containing 27,000 
7

ppm As and 20 ppm metaldehyde, cattle developed 

ataxia, profuse diarrhea, and muscle fasciculations.52 The 

authors suggested that most of the toxic effects were due 

to As because the predominate clinical signs did not fit 

metaldehyde. 

The toxicity of the herbicide, lead arsenate (PbHAsO4), 

is thought to be due to the As content rather than Pb.53-55

After licking bags containing PbHAsO4, cattle exhibited 

rapid pulse and respiration, oral mucosal erosions, diarrhea, and decreased milk production. Arsenic toxicity 

was confirmed when stomach contents were found to 

have 175 ppm As.53 Yearling cattle exhibited severe colic, 

diarrhea, and death after consuming an undetermined 

amount of a powder containing 39% Pb and 10% As. 

Rumen contents from the animals contained 478-531 

ppm As.56 Five calves began showing signs of lethargy, 

ataxia, anorexia, decreased heart rates, and diarrhea after 

consuming powder containing 700,000 ppm As2O3. 

Four of the animals eventually died.57 Cattle receiving 

67 g As2O3 and calves receiving 17 g As2O3 as a topically applied medication became depressed and exhibited 

bloody diarrhea and a staggering gait soon after treatment. By 20 hours post treatment, 94 of 101 animals 

were dead.58 Depression, ataxia, weakness, recumbency, 

diarrhea, abdominal pain, and tachycardia developed in 

15 cattle that ingested ash from As-preserved wood. The 

ash was found to contain 780 ppm As.59 After 260 heifers 

were moved to a new pasture containing an abandoned 

cattle dip, they became restless and belligerent and began 

showing signs of profuse salivation and watery diarrhea. 

(Watery diarrhea is extremely dilute and may even be 

clear; it’s usually a result of runaway secretory processes 

in the bowel.) More than 50% of the herd exhibited 

convulsions and became comatose, and 67 eventually 

died. The soil around the dip contained 10-150 ppm As 

and 50-500 ppm toxaphene. The authors suggested that, 

because tissue As concentrations were not diagnostically 

significant, the combination of As and toxaphene caused 

the die-off.60 Experimentally, four of five cattle died 

within 10 days of being dosed with 10 mg AsV/kg BW/

day as monosodium methanearsonate.61

More than 650 of 1,000 sheep developed diarrhea and 

died after consuming vegetation that had been sprayed 

with a PbHAsO4 solution containing 0.58 % As.62 The 

condition was reproduced by dosing lambs with 12 mg 

As/kg BW.62 Lambs showed signs of depression, abdominal pain, salivation, and diarrhea after ingesting forage 

containing 62-95 ppm As due to contamination with 

a cotton defoliant; 172 of 923 lambs died.63 Six doe 

white-tailed deer were found dead after eating soil and 

vegetation contaminated by aerial spraying of an arsenical 

herbicide at the rate of 1.6 lbs As per acre. Later analysis 

of a combined soil and vegetation sample yielded 2.4 

ppm As, and water samples yielded 0.36-0.48 mg As/L.64 

The application rate, however, calculates to a forage 

concentration of approximately 368 ppm or a dosage of 

approximately 11 mg As/kg BW in an animal consuming 

3 % BW daily. The latter numbers are more consistent 

with reported tissue concentrations (18-19 ppm As) in 

the dead deer than the soil and water analysis.

Arsenic poisoning has also been reported in monogastrics. 

Nine thoroughbred racehorses died after showing signs of 

extreme distress, weakness, colic, rapid, weak pulse, hyperemic mucous membranes, and watery diarrhea. It was 

discovered that roughly 8 oz. of arsenical rat poison had 

spilled into their corn bin. Post mortem chemical analysis 

discovered significant amounts of As in the stomach and 

liver of two horses.65 Working backward from the numbers presented, we estimate the horses received a dose of 

between 1-10 mg As/kg BW. Gastrointestinal cramps, 

vomiting, diarrhea, ECG changes, and liver disruption 

developed in a 27-year-old woman after she ingested 

9,000 mg As2O3.

66 Furr and Buck67 poisoned cats with a 

commercial ant bait. Doses of As (as Na2HAsO4) greater 

than 8 mg/kg BW were lethal; the threshold of toxic signs 

was 2 mg/kg BW, and the no-effect level was 1.5 mg/kg 

BW.

In swine, arsanilic acid has been frequently used as a 

growth promotant and as a treatment for swine dysentery. 

In several cases, excessive doses or prolonged treatment 

periods have resulted in a chronic syndrome characterized 

by apparent blindness due to degeneration of the optic 

nerve and optic chiasma.68-74 The toxic mechanism and 

toxicity of this class of arsenical drugs are quite distinct 

from and less than inorganic As and will therefore not be 

considered further. 

At present, despite convincing epidemiologic evidence 

that very low concentrations of As in drinking water can 

cause chronic disease, especially cancer, in human beings, 

there are no animal models that reliably duplicate these 

particular toxic effects without resorting to relatively high 

doses and/or pharmacologic and genetic manipulation 

to render them more sensitive.19,33 The current belief, 

derived from in vitro studies and specialized laboratory 

animal models, is that small amounts of DMAIII and 

MMAIII escape the methylation process in people and, 

over prolonged periods, cause cellular damage that results 
8

in diseases such as cancer.10,20,23,32,33,41,44 Dimethylarsinic 

acid (DMAV) and monomethylarsonoic acid (MMAV) 

are the main urinary metabolites of As excreted in most 

mammals; however, the trivalent As metabolites, dimethylarsinous acid (DMAIII), and monomethylarsonous 

acid (MMAIII) have been discovered in fresh urine of Aspoisoned human patients.20 The glutathione conjugate 

of DMAIII was actually more toxic to cells in vitro than 

inorganic As20, and DMAIII causes single-strand breaks in 

DNA in vitro.

20,75 These processes are apparently limited 

to human beings and specialized laboratory models; thus, 

based upon known differences in metabolism, this class of 

disease and dosages does not seem relevant for livestock 

and big game animals. 

Developmental studies of orally administered MMAV and 

DMAV (the metabolites of inorganic As in most nonhuman mammals) in rats and rabbits determined the 

threshold of fetal damage was similar to that for maternal 

toxicity or about 36 and 48 mg/kg BW, respectively.76 

Administration of As by gavage to pregnant rats and mice 

did not produce morphologically evident teratogenesis at 

non-maternally toxic dosages, although there was some 

evidence of behavioral changes in pups born to dams 

consuming drinking water with slightly less AsIII than the 

lowest maternally toxic dose.22 Conversely, Domingo77

reported that AsIII, via the oral route of exposure, was 

much less teratogenic in several species. This indicates 

that dietary limits safe for a dam should also provide 

adequate protection for her fetus.

There are very few reports of chronic toxicity in non-rodent animals. Due to the rapid excretion of As in cattle, 

sheep, dogs, etc., these species are able to clear less-thanacutely-toxic doses of As before they can cause much of 

a problem.25,78 The reports of chronic toxicity we discovered involved dosages similar to those reported for acute 

or subacute poisoning. Female beagle dogs fed 4 to 8 mg 

NaAsO2 (2.3-4.6 mg As)/kg BW per day for 183 days 

exhibited decreased weight gains due to decreased feed 

consumption and slightly elevated liver enzymes.79 Beagle dogs were fed varying concentrations of As as either 

AsIII or AsV for two years. At 50 ppm and less, there were 

no measurable effects. At 125 ppm dietary As, the dogs 

lost weight and several died with lesions of inanition.80

Three of four sheep given 88 mg PbHAsO4/kg BW once 

per month died within 24 hours of the seventh dose. The 

other sheep in the study, given 22 and 44 mg PbHAsO4

(4.9 and 9.7 mg As/kg BW), survived 11 doses with no 

clinical signs.54 One of two lambs dosed with 1.5 mg As/

kg BW/day as PbHAsO4 died after 35 days; the other 

survived until the study was stopped at 94 days.62 Sheep 

fed a mean daily dose of 1.4 mg As/kg (As species unspecified) for three weeks remained in good condition for 

the duration of the study.81 Bucy et al.82 fed potassium 

arsenite to feedlot lambs at doses as high as 3.26 mg As/

kg BW/day for eight weeks without adverse effects. In a 

later study 1.75 mg/kg BW/day was not toxic, but higher 

doses caused feed refusal and clinical signs of toxicity.83 

Peoples78 added arsenic acid to dairy rations at 1.25 ppm, 

a dose of approximately 0.48 mg As/kg BW/day for seven 

weeks with no effects. Virtually all of the ingested As was 

eliminated as quickly as it was eaten. 

It has been proposed84 that elk in the Madison-Firehole 

watershed of Yellowstone National Park have shorter 

lifespans because of naturally elevated As in water and 

feedstuffs. Exposure was estimated to be “greater than 

1.25 mg/kg BW/day” based upon tissue concentrations 

and extrapolation from bovine studies and between “0.01 

- 6.2 mg/kg BW/day” based upon forage and water analysis. The difference in longevity also may be due to other 

environmental differences between the Madison-Firehole 

area and the control site.84 Forsberg et al.85 demonstrated 

slight but measurable inhibition of normal rumen 

fermentation in vitro with As concentrations as low as 5 

mg/L of rumen fluid, but they did not provide any data 

as to how this concentration related to dietary intake. 

Assuming for the moment that the rumen fluid concentration is equivalent to the combined concentrations in 

feed and water, the concentration would be equivalent to 

a dose of roughly 1 mg As/kg BW.

Summary

Our recommendations are based upon the toxicity of inorganic AsIII, specifically the arsenite ion. Routine water 

quality analysis available to livestock producers does not 

distinguish between As species, and, although the less 

toxic pentavalent forms of As are more likely to occur 

in surface waters, trivalent As is seen frequently enough 

in specialized surveys to justify the assumption.86,87 It is 

suggested that ruminant animals are less susceptible to As 

than monogastrics.25,88 With the exception of laboratory 

rodents, however, we were not able to confirm this to be 

the case, thus we have assumed horses are equally sensitive to As as ruminants.

Chronic poisoning of the type (cancer, “blackfoot disease,” etc.) that prompted lowering the human drinking water standard from 0.05 to 0.01 mg As/L does not 

apparently occur in other animal species, as demonstrated 
9

by the ongoing search for an appropriate animal model to 

study the human condition. The mechanism(s) putatively involved in the pathogenesis of chronic damage in 

people, i.e. chemical attack by methylated AsIII metabolites on cellular macromolecules, do not appear to be 

relevant in livestock and wildlife. In domestic livestock, 

as opposed to people, most As is excreted via urine as 

DMAIII.

33 This, together with the shorter observed halflife in these species, suggests that relatively little trivalent 

As escapes methylation and excretion to cause cancer. 

Chronic poisoning in livestock species involves mechanisms similar to acute poisoning and requires dosages 

very similar to acute poisoning.

Given the accumulating evidence that As is a human 

carcinogen, the question of residues arises. Can food 

animals consuming As from water accumulate dangerous amounts of As in edible tissues without themselves 

showing signs of toxicity? The literature to date suggests 

cattle, sheep, etc. eliminate As too quickly for this to be 

a concern, and a study completed in 2007 by the University of Minnesota89,90 failed to find any evidence of As 

accumulation in milk or edible tissues from dairy cattle 

watered from As-contaminated (140 μg/L) wells.

The threshold toxic dose in domestic ruminants appears 

to be between 1-2 mg/kg BW. This dose is in general 

agreement with the NRC25, which recommended 30-50 

ppm dietary As as a maximum tolerated dose and with 

other reviews.88,91-93 It is quite distinct from the EU 

recommendation of 2 ppm dietary As, for which we have 

not been able to discover any justification. Sufficient 

quantitative data was not found to estimate a similar 

threshold for horses, but this dose is similar to that reported in another monogastric species (dogs)79, and previous reviews suggest horses are similar to cattle in sensitivity and/or less frequently affected than cattle under similar 

conditions.93,94 Therefore, it seems reasonable that limits 

safe for cattle should be adequate for horses. The very 

limited data in wild ruminants suggest they are similar to 

cattle in sensitivity. Therefore, our recommendations are 

based upon dosage data from cattle and sheep. Assuming 

neglible As in feedstuffs, 5 mg As/L in drinking water will 

provide the minimum toxic dose of 1 mg As/kg BW to 

grazing animals in warm weather. Obviously, if animals 

are receiving any As from forage or medications, less will 

be required to achieve a toxic dose. Although we were 

not able to find any significant studies of As in Wyoming 

forages, limited data from our laboratories suggest natural 

background concentrations seldom exceed a few ppm, 

except in areas contaminated by geothermal runoff. 

Assuming a NOAEL of 0.5 mg/kg BW/day and allowing for these small forage concentrations, we recommend drinking water for livestock and wildlife not 

exceed 1 mg As/L.
10
11

Barium (Ba), an alkaline earth element, oxidizes easily when exposed to air, and it is found as the Ba2+ ion 

in water. Barium found in surface and ground waters 

is predominantly derived from weathered rock and 

minerals. Common naturally occurring Ba minerals are 

insoluble barite (barium sulfate, BaSO4) and somewhat 

more soluble witherite (barium carbonate, BaCO3), while 

the Ba2+ ion is most common in natural waters.95 Barium 

concentrations in water will likely be higher near drilling 

platforms than natural background concentrations as 

a result of drilling muds, cuttings, and produced water 

discharge containing Ba.96 In water, soluble Ba may 

precipitate out of aqueous solution as insoluble salts (e.g. 

BaSO4 and BaCO3). At pH activity of 9.3 or below, 

the formation of BaSO4 limits the Ba concentration in 

natural waters. Barium has a variety of uses: BaSO4 is 

used in patients for digestive tract imaging and for oil 

drilling, and BaCO3 is used in rodenticides.96-98 

Essentiality

Barium is not an essential element for plants or animals. 

Metabolism

Existing studies indicate Ba absorbed from the G.I. tract 

is primarily deposited in bones and teeth and excreted via 

feces and urine.99-103 The absorption efficiency of various 

Ba compounds given orally varies widely (0.7-85%) depending upon the chemical form, species, age, and fasting 

status of the animal.104-106 In general, more soluble forms 

of Ba such as barium chloride (BaCl2) are more readily 

absorbed. Young rats absorb approximately 10 fold more 

BaCl2 than adults.106 Barium disappears from blood and 

milk with a half-life (t1/2) measured in days;100,102 however, 

Ba deposited in bone has a t1/2 measured in years, and 

disappearance from bone is generally dependent upon 

bone turnover.107 These observations, together with the 

divalent cationic nature of Ba and the fact Ba is known to 

bind Ca-dependent enzyme systems in cells, suggest Ba 

metabolism utilizes Ca transport systems in the body. 

Toxicity

Barium is toxic in water-soluble forms such as BaCl2 and, 

to a lesser extent, BaCO3. Barium sulfate is insoluble and 

is not considered hazardous to people or other monogastric animals. The specific toxic mechanism of Ba is 

a blockade of passive transmembrane potassium (K+) 

conductance in excitable cells by the Ba2+ ion.97,98,108,109 

Barium also competes with and/or mimics the functions 

of Ca in muscle contraction and in second messenger 

pathways.97,108 The characteristic systemic effect of Ba 

poisoning is “violent contraction of smooth, striated, and 

cardiac muscle.”109,110 Clinically, this effect is manifested 

as arterial hypertension and premature supraventricular and ventricular contractions, followed by skeletal 

muscle contraction, salivation, vomiting, colic, and diarrhea.97,98,108,109,111,112 Subsequently, blood pressure drops 

precipitously and skeletal muscles exhibit flaccid paralysis. Finally, death results from arrhythmias and cardiac 

failure.104,112,113 The hypokalemia seen in Ba poisoning 

is thought to result from blockade of passive K channels 

and intracellular sequestration, as Ba has no proven activity on the Na+

K+ATPase pump.98,109,114 

Data on the toxicity of Ba in grazing animals is limited. 

Two ruminally fistulated dairy goats were infused with 

5mM BaCl2 at a rate of 60 ml/hr. The ruminal fluid Ba2+

ion concentration was estimated to be 0.4 mM assuming 

no absorption or precipitation occurred. After receiving 

Ba2+ for six hours, the animals exhibited weakness and 

paralysis, and they died later that night. The resulting 

oral lethal dose of BaCl2 in the goat was determined to 

be less than 4.6 mg Ba2+/kg BW.115 This Ba dosage would 

equate to approximately 23 mg/L in drinking water under conditions outlined in the Introduction. Ba poisoning occurred during two successive years in cattle that 

were trailed through an abandoned lead/silver mine site 

containing a Ba-contaminated pond.116 Affected animals 

exhibited protruding tongues, salivation, watery diarrhea, 

muscle tremors, and paralysis progressing to recumbency 

and death. Six of 30 animals died the first year and 16 

of 20 the second. Liver and kidney tissues from affected 

animals contained elevated Ba concentrations, and other 

metals (Pb, As, Se, etc.) were within normal limits. Pond 

water contained 2.2 mg Ba2+/L; however, clay found in 

3 Barium
12

both the abomasum of the dead cattle and in the pond 

contained 69,000 ppm Ba. The amount of Ba, if any, 

absorbed from the clay is presently unknown. X-ray diffraction analysis of the clay indicated the Ba was present 

primarily as insoluble BaSO4, with lesser amounts of 

BaCa[CO3]

2

 and BaCO3 salts. Reagor117 fed BaCO3 to 

steers at 0.4% and 0.8% of the dry matter diet to steers 

(0.28% and 0.56% Ba respectively). All three receiving 

the high dose died after a single day on feed; all three receiving the lower concentration remained healthy for the 

duration of the experiment. Clinical signs in the steers 

were similar to those reported in monogastrics.

Malhi et al.118 investigated the optimum concentration of 

BaCO3 for a rodenticide and concluded 1.5 g of BaCO3

per 100 g body weight (or 15,000 mg/kg) was the most 

efficient rat poison. There was no attempt to determine 

a minimum lethal dose. Mattila et al.119 administered 

BaCl2 via the marginal ear vein of six rabbits instrumented with an electrocardiograph. Three to 5 mg Ba2+/kg of 

BW caused dysrhythmias with and without convulsions. 

Rabbits receiving 3 mg Ba2+/kg of BW survived, despite 

convulsions. Roza and Berman112 observed anesthetized 

dogs after infusing them with 0.66-2.64 μmol Ba (as 

BaCl2)/kg/min to identify mechanisms of Ba-induced 

hypokalemia and hypertension and to study the Ba-K 

interaction on the heart in vivo. They found rates greater 

than 4 μmol BaCl2/kg/min (~362 μg Ba2+/kg/min) were 

fatal within a few minutes due to respiratory paralysis. 

In humans, most acute oral toxicity data is derived from 

suicide attempts. Gosselin110 describes the oral lethal 

dose in humans as “1-15 g.” A research chemist attempted suicide by ingesting a teaspoon (approximately 13 g) 

of BaCl2.

120 He was rushed to a hospital and survived 

after treatment with MgSO4 and KCl. Seven members of 

a family were poisoned with Ba after ingesting fried fish 

accidentally breaded with powdered rat poison.114 The 

exact amount of BaCO3 ingested was not determined, 

but the breading of the fish contained 105,000 ppm of 

Ba. Three of the family members displayed classic signs 

of Ba poisoning, while one developed rhabdomyolysis, 

respiratory failure, and hypophosphatemia. All patients 

survived with treatment. In another instance, a 26-yearold man consumed one can of “Magic Shave” containing 

12.8 g of Ba2+ ion and 3 g of sulfide.121 Ipecac was given 

within three hours. He suffered respiratory paralysis, 

severe respiratory acidosis, and hypokalemia. His condition improved after he was given 206 meq of K over 19 

hours. 

Several studies have examined the chronic oral toxicity 

of low concentration BaCl2 in drinking water to people 

because of Ba’s recognized cardiac toxicity. Wones et 

al.122 concluded that drinking water concentrations of 5 

and 10 mg Ba2+/L did not affect any known modifiable 

cardiovascular risk factors. Eleven healthy men were 

given BaCl2 in their drinking water for six weeks. For the 

first two weeks of the experiment, no BaCl2 was added to 

their water. BaCl2 was then added at rates of 2-5 mg/L 

for the next four weeks and 10 mg Ba/L for the last four 

weeks. The subjects were given 1.5 L of treated drinking water per day; any additional drinking water was 

distilled. Diets were controlled as well as other known 

causes of cardiovascular disease. Blood (plasma total 

triglycerides and HDL cholesterol), urine (Na, K, vanillymandelic acid, and total metanephrines), blood pressure, 

and cardiac function were monitored throughout the 

study. They discovered no apparent changes in modifiable cardiovascular risk factors, but there was a trend 

toward slightly increased total blood Ca. Brenniman and 

Levy123 conducted an epidemiological study to determine if mortality and morbidity rate were significantly 

increased in human populations drinking elevated Ba 

levels in their drinking water as compared to populations 

with little or no Ba exposure. Cardiovascular mortality 

rates were surveyed in communities with drinking water 

Ba concentrations that ranged between 2-10 mg/L. A 

morbidity study was also conducted in areas where mean 

Ba concentrations in drinking water were 0.1 and 7.3 

mg/L. They found higher cardiovascular mortality rates 

in elevated Ba communities, but there were also several 

confounding variables. There were no significant differences in blood pressure, hypertension, stroke, and heart 

and kidney disease. 

The single oral LD50 of BaCl2 in rats was estimated to be 

approximately 264 mg Ba/kg BW.124 Short-term (1-10 

day) oral exposure to BaCl2 at daily doses up to 138 mg 

Ba/kg BW produced no significant adverse health effects. 

Because of the link with cardiovascular disease in people, 

most chronic laboratory animal studies focus on cardiac effects. Barium acetate (Ba(CH3

COO)2), added to 

drinking water at 5 mg Ba2+/L and fed to rats over their 

lifespan had little or no effect on growth, carcinogenesis, 

or longevity.125 Rats drinking water with 100 mg Ba2+/L 

as BaCl2 for 16 months exhibited significant but varying increases in systolic blood pressure.126 In a similar 

study, the average systolic pressure increased significantly 

after exposure to 100 mg Ba2+/L for one month and after 

10 mg Ba2+/L for eight months. After 16 months, rats 
13

exposed to 100 mg Ba2+/L had depressed heart rates and 

decreased cardiac function.127,128 Another experiment examined the effect of BaCl2

 in drinking water for 92 days 

on serum electrolytes, body weight, behavior, and fertility 

in rats and mice.129 The no observed adverse effect level 

(NOAEL) for Ba, based upon depressed body weight 

gain and renal and lymphoid lesions, was estimated to 

be 1,120 mg Ba2+/L. Mortality was attributed to kidney damage. There appeared to be no adverse effects on 

reproduction and fertility, although there was a marginal 

reduction in pup weights. Tardiff et al.130 studied acute 

oral and subchronic toxicity of Ba as BaCl2 in rats. The 

acute oral LD50 for weanling rats was 220 mg Ba/kg BW 

and for adults was 132 mg Ba/kg BW. Drinking 250 mg 

Ba2+/L for up to 13 weeks resulted in less water consumption than controls, but it did not cause any clinical signs 

of toxicity, nor was body weight affected. McCauley et 

al.131 found no significant lesions in rats exposed to up to 

250 mg Ba/L drinking water for 68 weeks, nor were there 

measurable electrocardiographic changes when measured 

at five months; however, Ba-exposed rats were more sensitive to norepinephrine. 

An anecdotal report of BaCl2 ingestion in a man suggests 

Ba may damage kidneys, although the kidney lesions were 

likely the result of IV therapy with MgSO4.

120 Chronic 

Ba exposure causes nephropathy in rodents. Male rats 

drinking 5 ppm Ba as the acetate salt in a life-time study 

developed proteinuria.125 McCauley et al.131 identified 

kidney lesions in rodents administered 1,000 mg Ba/L 

in drinking water for 16 weeks. Dietz et al. identified 

kidney lesions in male and female mice receiving doses of 

436-562 mg Ba2+/kg BW/day via drinking water for 92 

days. Rats receiving the same water drank less, receiving 

only about one quarter of the dose and had much milder 

renal lesions.129 In a subsequent two-year cancer bioassay, female and male rats receiving 75 and 60 mg Ba2+/kg 

BW/day, respectively, in drinking water gained less than 

controls but did not exhibit any Ba-related clinical signs. 

Mice in the same two-year study drank up to 160 (male) 

or 200 (female) mg Ba2+/kg BW/day and had significantly 

greater premature mortality due to kidney disease than 

did controls.132

Most authorities indicate BaSO4 is the least soluble and 

therefore least toxic form of Ba. A United Kingdom 

risk assessment of BaSO4 described it as a low risk due 

to, among other reasons, low solubility.133 Studies by 

Maglinte et al.134 and several decades use of BaSO4 as radiographic contrast media support the premise BaSO4

 is 

relatively nontoxic in mammals.134-137 Ba sulfate-derived 

Ba was poorly bioavailable in an environmental study and 

thus did not bioconcentrate between trophic levels in the 

food-chain.138 One exception is a study suggesting 131Ba 

from BaSO4 was nearly as bioavailable as BaCl2.

139

There are a number of reports regarding the toxicity of inhaled Ba.140-143 Since the relationship between the toxicity 

of inhaled Ba and soluble Ba in feed or water is not fully 

understood, these studies were not included. 

Summary

The acutely toxic effects of Ba are similar in monogastrics 

and ruminants. This argues that 1) Ba is a valid water 

quality concern for livestock and wildlife, and 2) subacute 

and chronic effects are probably similar, if not identical, 

between these species. The putative toxic mechanism(s) 

of the Ba2+ ion in rodents and human beings involve 

physiologic mechanisms that are highly conserved (i.e. 

very similar) throughout terrestrial mammals; therefore, 

any species-specific differences in toxicity logically derive 

from species-specific differences in the toxicokinetics of 

Ba. In monogastric mammals, the oral toxicity of Ba 

compounds correlates with their water solubility. Less 

soluble forms of Ba (notably BaSO4) are poorly absorbed 

and are thus considerably less toxic than more soluble 

salts such as BaCl2, barium nitrate (Ba(NO3)

2

), or barium 

hydroxide (Ba(OH)2).105 There is no equivalent data in 

ruminants. Theoretically, reduction of the SO4 salt to 

sulfide by rumen microflora might result in increased 

bioavailability of the Ba2+ ion. There is some precedent 

for differences in metabolism of Ba between monogastrics 

and ruminants144, but much more needs to be done. As 

a practical matter, however, this theoretical effect would 

be significant only in solid feedstuffs as insoluble forms of 

Ba (i.e. BaSO4) will presumably not be present in drinking water in any significant concentration.

The long-term effects of Ba, especially on reproduction, have been incompletely investigated in any species. A single Russian report of Ba inhalation toxicity 

describes reproductive lesions in both male and female 

rats145 whereas more recent rodent studies did not note 

alterations in reproductive tissues or reproductive function following acute-, intermediate- or chronic-duration 

exposure to Ba.129,131,132 Kidney damage was observed in 

laboratory rodents following two-year exposure to 200 

mg Ba/kg BW and in long-term (91-day) oral exposure to 

450 mg Ba/kg BW, but it was not seen after administration of 250 mg Ba/kg BW for 36-46 weeks.131,132 
14

The only quantitative data available in cattle indicates 138 

mg Ba/kg BW, as BaCO3, in dry feedstuffs was acutely 

toxic to steers, whereas 69 mg Ba/kg BW was not.117 Assuming water consumption of 20% BW, this translates to 

690 mg Ba2+/L in drinking water as being acutely toxic or 

345 mg Ba2+/L as the NOAEL. This contrasts with the 

report of Richards et al.116 that 2 mg soluble Ba2+/L water, 

plus some undetermined amount of Ba from sediment, 

was immediately toxic to cows and calves. It is also much 

higher than the toxic dose reported in goats, where 7 mg/

kg BW BaCl2 (4.6 mg Ba/kg BW) was lethal.115 It is likely 

that BaCO3 in feed is not as bioavailable as the Ba2+ ion 

in water. The acutely lethal dose in the goat study translates to 23 mg Ba2+/L under the assumptions outlined in 

the Introduction. 

Obviously, much more research needs to be done 

with Ba in ruminants, but, given the current state of 

knowledge, soluble Ba2+ concentrations should be held 

to well below 23 mg/L to avoid acute toxicity. There is 

absolutely no data on chronic Ba2+ ion toxicity in any 

of our species of interest. This, plus the limited and 

conflicting data from chronic studies in other animals, 

makes it impossible to postulate a long-term “safe” 

level of the Ba2+ ion in drinking water for domestic 

livestock and/or wildlife species with any degree of 

certainty. 

We do not recommend using water containing more 

than 10 mg Ba2+/L even for short periods. Until 

there is better data, it is impossible to make any 

recommendations regarding chronic exposure.
15

Fluorine (F) is the most electronegative and reactive of 

known elements. It rarely occurs free in nature, chemically combining to form fluorides. Fluorides are widely 

distributed throughout the environment in various 

anthropogenic and natural forms. Mineral forms of F include cryolite (Na3

AlF6), fluorite (CaF2), and fluorapatite 

(Ca5(PO4)

3

F). Vegetation can accumulate fluoride from 

soil, water, and the atmosphere.146 In aqueous environments, F occurs as the free fluoride ion (F-

) and is mobile, 

especially in alkaline waters.95 Unless surface waters are 

contaminated by a F- source, ground waters tend to have 

higher concentrations of F- than surface waters.

Essentiality

The NRC147 describes F- as an “important constituent” of 

bones and teeth, and, although essentiality has not been 

proven, small amounts have been added to municipal 

water supplies to improve dental health for decades. Apparently, even if F is essential, the dietary requirement is 

so small it is easily met by even highly purified diets. As 

noted by Ammerman,148 “Whether or not it is essential 

for animals may be open to debate... The fact that it is 

toxic is more easily confirmed.” 

Metabolism

Fluoride is readily absorbed by the stomach, rumen, and 

small intestine. The efficiency of absorption depends 

upon the solubility of the specific F compound, other 

dietary components, and the species, sex, and age of 

the animal.147,149 Conditions that result in very low pH 

favor the formation of hydrogen fluoride (HF), which is 

lipophilic and thus diffuses easily across lipid membranes. 

The F- ion is absorbed in the small intestine via a pH 

independent process.147 Soluble fluorides, i.e. the F- ion 

in water, are almost 100% absorbed. Less soluble sources 

such as F compounds in bone meal are relatively poorly 

absorbed. Ca, Mg, Al, NaCl, and high lipid concentrations are known to depress F uptake.147,150

Two mechanisms are responsible for removal of F- from 

the systemic circulation: renal excretion and deposition 

in calcified tissues. After absorption, most F- circulates 

in plasma as ionic F-. To a lesser extent, it circulates as 

4 Fluoride

CaF2 or HF, or it is bound to protein.150-152 Circulating 

F- represents a relatively small portion of the total body 

burden but is the form most easily exchanged with other 

tissues and/or eliminated via renal filtration.151,152 Urinary excretion is the primary route of elimination and 

is directly related to urinary pH; thus, factors that affect 

urinary pH influence how much F- is excreted.150,153 

Under “normal” circumstances, roughly 50% of ingested 

F- is eliminated immediately, and the remainder is incorporated into bony tissues147; however, these percentages 

may be significantly modified by physiologic factors such 

as age, sex, or other factors. Calcified tissues such as 

teeth and bone have a great affinity for F-, incorporating 

it as fluorapatite in place of hydroxyapatite in the calcified matrix.147,153 To a certain extent, bone deposition 

represents a form of detoxication by decreasing the Fexposure of other tissues. Fluorapatite crystals, however, 

are less soluble than the hydroxyapatite they replace and 

thus 1) persist for long periods in bone, and 2) interfere 

with normal turnover (remodelling) of bone. Therefore, 

at higher concentrations, bone F- interferes with normal 

physiological processes like growth and healing. Since Fdeposition in skeletal tissues is related to the turnover of 

bone minerals, young, rapidly growing animals are more 

likely to accumulate it.147

Toxicity

Animals can ingest potentially toxic doses of F- from a 

variety of sources. In the past, forages contaminated by 

aluminum smelters or grown in naturally high F- soils, 

rock phosphate fed nutritional supplements, and/or consumption of naturally high F-

 water have resulted in Fpoisoning.147,149,154-156 Large doses of soluble Fcan form 

corrosive HF, interfere with ion gradients in excitable 

cells, and/or precipitate divalent cations from serum.157,158 

Thus, acute fluorosis is manifested as gastroenteritis, 

cardiac arrhythmias, and/or collapse.157 Chronic or subchronic exposure to somewhat lower doses results in kidney damage,157,159,160 neurologic damage, or reproductive 

failure.161-163 The most sensitive (i.e. occur at the lowest 

dose) clinical manifestations of F- toxicosis in livestock 

and wildlife under real-world conditions are tooth and 

bone deformities.149,164-169 These bony tissue lesions often 
16

result in difficulty grazing, reduced feed intake, ill-thrift, 

and decreased performance.149,166,167 Alternating periods 

of high and low F- exposure are more toxic than a continuous intake of the same average amount. Nutritional 

status and the age when exposed to F- also influence 

tolerance.170

The effect of F- on behavior and brain development was 

examined in rats by injecting pregnant dams with 0.13 

mg/kg BW of sodium fluoride (NaF) subcutaneously on 

gestational days 14-18 or 17-19.171 Weanlings received 

either no NaF or NaF in drinking water at 75, 100, or 

125 mg F-/L for six or 20 weeks, and three 3-monthold adults received water containing 100 mg F-

/L for 

six weeks. Rats exposed to F- had sex-and dose-specific 

behavioral deficits. Males were most sensitive to prenatal 

exposure; females were more sensitive to weanling and 

adult exposure. Drinking water containing 125 mg F-/L 

resulted in reduced growth, and 175 mg F-/L was lethal. 

Shan et al.172 treated rats with differing concentrations of 

F to investigate the effect of F- on cognitive processes by 

examining its effects on nicotinic acetylcholine receptors 

(nAChRs) in the brain. Both 30 and 100 mg F-/L in the 

drinking water produced subtle brain damage indicative of oxidative stress. Paul et al.173 administered NaF 

by oral intubation daily at 20 or 40 mg/kg BW to adult 

female rats for 60 days and measured spontaneous motor activity, motor coordination, cholinesterase activity 

in blood and brain, and the protein content of muscle, 

liver, and serum. Sodium fluoride treatment suppressed 

spontaneous motor activity and tissue and serum protein 

concentrations in a dose-dependent manner. Wang et 

al.174 found decreased total phospholipid concentrations 

and ubiquinone in rat livers due to oxidative stress after 

seven months of consuming water containing 30 or 100 

mg F-/L. 

Rats were offered drinking water containing 225 mg 

F-/L as NaF for 60 days.175 A second group of rats was 

also gavaged with calcium carbonate (CaCO3). The 

NaF-treated rats exhibited decreased food and water 

intake, reduced body weight gain, and impaired nervous 

function. Fluoride-induced dental lesions, inhibition 

of acetylcholinesterase and N+ K+ ATPase activity, and 

decreased serum protein improved after NaF withdrawal. 

Calcium treatment lessened the impact of F by decreasing serum F concentrations.175 Rats given drinking water 

with either 30 or 100 mg F-/L as NaF for seven months 

had decreased kidney proteins and BW gains, and dental 

fluorosis.159 Ten or 30 mg F-/L administered to male rats 

via drinking water for three to six months did not cause 

any overt clinical effects but did produce biochemical indications of liver damage.176 Oral administration of NaF 

in water at 5 or 10 mg (2.25 or 4.5 mg F-)/kg BW/day 

for 30 days to adult male rats resulted in reduced body 

weight.163 Testicular cholesterol and serum testosterone 

levels were not affected, but sperm motility and count 

were decreased resulting in a significant decline in fertility. Heindel et al.177 studied fetal development in rats 

and rabbits fed up to 300 or 400 mg NaF (135 or 180 

mg F-)/L drinking water, respectively, during gestation. 

Although there were no teratogenic effects at any dose, 

dams lost weight after drinking water with concentrations greater than 150 mg NaF/L (rat) or 200 mg NaF/L 

(rabbit).

Certain elements are known to interfere with the uptake 

of F, a fact some have attempted to exploit therapeutically. Rats received drinking water treated with equivalent 

amounts of F as aluminum fluoride (AlF3, 0.5 mg/L) or 

NaF (2.1 mg/L) for 52 weeks to evaluate the interaction 

of Al with F.178 AlF3e reduced the neuronal density of the 

brain neocortex compared to the NaF and control rats. 

Brain and kidney Al concentrations were higher in both 

AlF3- and NaF-treated groups than in controls. Rabbits 

were fed drinking water containing various combinations 

of either F- (1-50 mg/L as NaF) or Al (100-500 mg/L as 

AlCl3) for 10 weeks. Although none of the treatments 

resulted in significant weight loss, Al treatment decreased 

F- accumulation in bone. Surprisingly, F-, by itself, increased bone Al concentrations, suggesting Al or an Al-F 

complex play a role in osteofluorosis.179 Kessibi et al.

180

gavaged sheep with 0, 1.9, or 4.7 mg F-/kg BW, with or 

without 13.5 mg Al/kg, for 33 months. In all treated 

animals, the general health status declined and osteodental signs appeared while F-

 levels increased in teeth, 

bones, and organs. In sheep given 4.7 mg F-/kg BW, 

lesions were observed in kidney and liver. Aluminum sulfate ((Al2

(SO4)

3

) alleviated some, but not all, of the effects 

of 1.9 mg F-/kg BW.

Rats and mice were fed no NaF in drinking water or at 

11, 45, or 79 mg F-/L for up to two years in a carcinogenesis bioassay.181 Body weights and survival rates of 

F- treated rats and mice were similar to controls. Osteosarcomas occurred in a small, statistically, and historically 

insignificant number of male rats at the highest dose, 

while there was no evidence of carcinogenic activity in 

female rats or mice of either sex. Rats on the highest 

two dosages also exhibited some increased osteo- and 

dental fluorosis.181 Deer mice captured and fed 38, 

1,065, 1,355, or 1,936 ppm dietary F- for eight weeks 
17

lost weight and many died at the highest dose.182 The 

toxicological response and metabolism of F- by three 

species of wild mammals (two species of voles and wood 

mouse) were compared to laboratory mice.183 Animals 

were given no NaF or 40 or 80 mg F-/L as NaF in their 

drinking water for up to 84 days. Forty and 80 mg F-/L 

treatments caused mortalities in the voles, probably as a 

result of the greater water intake of this species. Severe 

dental lesions were apparent in all animals surviving the 

80 mg F-/L treatment. 

Osteo-dental fluorosis was observed in cattle, buffalo, 

sheep, and goats from several villages in India where the 

mean F- concentration in drinking water ranged between 

1.5 to 4.0 mg/L.164 Forage F- concentrations were not 

measured, but the situation described suggests only 

background concentrations were present. The prevalence 

and severity of skeletal fluorosis increased with increasing F-

 concentration and age. Cattle and buffalo near 

a phosphate plant in India developed dental and bony 

lesions due to fluorosis.184 Lesions were more common in 

older animals than younger and in buffalo than in cattle. 

Environmental F- concentrations were: 534 mg F-/kg in 

fodder, 1.2 mg F-/L in pond water, and 0.5 mg F-/L in 

ground water, which, assuming standard consumption 

of forage and water, would have provided approximately 

14 mg F-/kg BW. Two ranches, one with drinking water 

containing up to 10.5 mg F-/L, the other with 3 mg/L, 

were compared in Argentina.185 While both had similar 

forage F- values (~15-25 ppm), cattle from the former 

exhibited excessive dental erosion. Neeley and Harbaugh186 studied a Texas dairy herd drinking 4-5 mg F-

/L 

before and after management changes that resulted in 

increased F- intake from 0.52 mg/kg BW to 1.69 mg/kg 

BW, primarily as a result of increased water consumption. 

Most animals exhibited dental fluorosis both before and 

after the change, but breeding efficiency and production increased after the change, probably as the result of 

better nutrition and management. Rand and Schmidt187

followed several Arizona herds’ drinking water containing 

16 mg F-/L and consuming forage containing up to 25 

ppm F-. They concluded 1 mg F-/kg BW can be tolerated 

for 5-10 years with only minor cosmetic effects, but 2 mg 

F-/kg BW will result in accelerated tooth wear and signs 

of osteofluorosis. After the Lonquimay volcano erupted 

in Chile, animals were exposed to water concentrations 

less than 2 mg F-/L and as much as 48 ppm F- in forage. 

Two years later cattle were still developing fluorosis.188

Cattle fed a contaminated supplement that provided 

between 0.7-1.6 mg F-/kg BW/day for a year developed 

bone lesions and dental fluorosis.189

Merriman and Hobbs190 conducted an extensive five-year 

study of the interactions between soil and water F- and 

nutrition in cattle. Cattle on pastures with average forage 

concentrations of 143 ppm F developed dental fluorosis. 

Fluoride in soil, water, and grasses reportedly did not 

affect gain, but the experimental design was too small to 

reliably detect differences in performance. Suttie et al.191

fed dairy calves 1.5 or 3 mg F-/kg BW, either continuously or in a six-month rotation, for six years. Bone Fwas related to total intake and urinary F-

 remained high 

during the “off” period, but dental lesions were related 

to the F- concentration when teeth were being formed. 

None of the treatments “affected growth or reproduction,” but only a small number of animals was studied. 

The physiologic effects of forage contaminated by fumes 

from an aluminum smelter and NaF-treated forage were 

examined in cattle.192 Gains were significantly less on 

diets containing more than 200 ppm F- as NaF. Cattle 

receiving 70-100 ppm F- exhibited decreased reproductive efficiency indirectly attributed to dental fluorosis. 

Cattle were fed 134 ppm dietary F- as soft phosphate or 

CaF2, or 67 ppm F- as NaF for 91 days to compare the 

bioavailability and toxicity of the different sources of F. 

Feed consumption, average daily gains, and feed conversion were not influenced by source of F-193; however, 

the study was too short to detect dental effects, and no 

controls were included. Shupe et al.194 summarized 30 

years of experimental and observational studies in cattle, 

sheep, horses, deer, elk, and bison exposed to differing 

F- concentrations. They concluded that excessive dietary 

F- during tooth formation damages teeth, and the abnormal wear of these teeth results in impaired performance. 

Offspring from F--damaged animals showed no signs of 

fluorosis. Short-term exposure of dairy heifers to 2.5 mg 

F-/kg BW during 13-15 or 16-18 months of age resulted 

in severe dental fluorosis, even though the total F intake 

was not excessive.195 Eckerlin et al.196 and Maylin et al.197

described a farm where F--contaminated concentrate 

contributed approximately 12.8 to 56 ppm F- to the diet. 

Cows had depressed milk production, while their calves 

exhibited dental and osterofluorosis and had severely 

stunted growth. 

Holsteins were raised and maintained for 7.5 years on 

forage containing 12, 27, 49, or 93 ppm F- as NaF.198

Initially, F had no effect on feed intake, digestion coefficients, or nutrient absorption. However, after the cows 

had been through two lactations, cattle consuming the 

higher two F- diets consumed and digested less. The “tolerance level” for dietary F was concluded to be between 
18

27-49 ppm of the total diet. McLaren and Merriman199

monitored beef cattle maintained on “high” (125 ppm) 

or “low” (37 ppm) F pastures and “good” (80-100% of 

NRC recommendations) or “poor” nutrition in a 2x2 factorial experiment. They concluded neither F-

 concentrations nor plane of nutrition had any effect on the “general 

health” of the animals. Sixteen dairy heifers were fed hay 

containing 10 or 62 ppm F- or 10 ppm hay supplemented with CaF2

 at 69 ppm F- or NaF at 68 ppm F-, for 588 

days.200 The F- diets resulted in dosages of 1.14, 1.32, or 

1.29 mg F-/kg, respectively. Calcium fluoride was less 

toxic than contaminated hay or NaF. Fluoride caused 

no adverse effects on soft tissues but did cause significant 

damage to teeth and bones. Van Rensburg and de Vos201

fed cows 5-12 mg F-/L in drinking water, with or without 

superphosphate, through four breeding seasons. By the 

second season the 8 and 12 mg F-/L groups exhibited 

prolonged post-parturition anestrus, and fertility declined 

in those two groups during the third season. By the 

fourth season toxic effects were apparent in the 5 mg F-/L 

group as well. 

Sheep were maintained on 2, 5, or 10 mg F-/L drinking water from natural sources for four years.202 The 

highest dose affected wool production, probably as a 

result of limited food consumption caused by dental 

fluorosis. Pregnant ewes drinking 10 mg F-/L water 

did not transmit toxic quantities of F- to the fetus or to 

the lamb through milk. Sheep fed a commercial, nondefluorinated, rock phosphate lick to provide 2 mg F-

/kg 

BW showed signs of fluorosis.203 Thirty-seven % of the 

commercial flock was affected, as opposed to only 17% of 

the breeding animals of the same age that were in better 

nutritional condition. Cattle and sheep raised on South 

African farms where water F- ranged from 4-26 mg/L and 

forage from 5.3-22.4 ppm experienced severe osteo- and 

dental fluorosis.204 Assuming normal consumption of 

forage and water, the dose received was between 2-4 mg 

F-/kg BW. A ranch in New Mexico experiencing dental 

fluorosis was discovered to have water sources varying from 0.09-3.32 mg F-

/L. Interestingly, the higher 

concentrations occurred in wells only used during part of 

the year, and a child drinking from the highest well had 

dental fluorosis as well.205

Horses and swine are believed to be less susceptible to 

fluorosis than cattle and sheep, but there is little clinical 

and no experimental data to support the contention.147 

Horses grazed in F- contaminated areas developed similar 

fluorotic signs as cattle and sheep.206 Swine received no 

NaF or were fed 200 or 1,000 ppm dietary F- as NaF 

for 45 days in an experiment to determine the effects 

of F- on bone growth.207 The higher concentrations of 

F- produced dose-related decreases in bone growth, feed 

consumption, and overall growth. Bones from F--treated 

pigs were less dense and exhibited growth plate abnormalities. 

Fluoride toxicosis was diagnosed in elk, deer, and bison 

on the basis of lesions and F- concentrations in teeth 

and bones collected by hunters in Utah, Wyoming, and 

Idaho. Vegetation and water samples collected from 

areas where fluorotic animals were discovered contained 

5.5-430 ppm F- and 0.5-24 mg F-/L, respectively.208 The 

investigators concluded that geographic areas where domestic livestock have chronic fluorosis are also problematic areas for wildlife, which implies wildlife are roughly 

equally sensitive to F. Suttie et al.209 studied deer near 

a new aluminum smelter where forage concentrations 

ranged from 1-30 ppm F-. All deer had increased dental 

F- and some mild cosmetic fluorosis, but none exhibited 

excessive tooth wear. Tissue F- concentrations in deer 

diagnosed with fluorosis on the basis of dental lesions 

near an aluminum smelter were similar to those reported 

for cattle.210 Suttie et al. fed 25 or 50 ppm F- as NaF to 

whitetail deer fawns.211 Fluorotic lesions were similar to 

those in cattle fed the same amount, but cattle seem to 

develop more bony lesions and fewer dental lesions than 

deer. Vikoren et al.212 surveyed several hundred jawbones 

from moose, red deer, and roe deer near aluminum smelters where forage concentrations averaged 30 ppm F-

, and 

they also looked at a small number of sheep in the same 

area. Although the overall incidence of fluorosis was low, 

tissue concentrations were similar in sheep and cervids, 

and the threshold bone F- concentration for disease in 

cervids was similar to what was previously reported in 

domestic species. 

Summary

Fluoride generates considerable controversy in human 

health, largely as a result of the common practice of 

fluoridating municipal water supplies. We were not, 

however, able to find any convincing experimental studies that suggested the dramatic effects associated with 

acute exposure to relatively large doses of F- carried over 

to low level, long-term exposure. Although there are a 

few reports of dental fluorosis in people at slightly lower 

concentrations, the current primary drinking water standard for human consumption is 4 mg F-

/L; the secondary 

standard, apparently based upon cosmetic dental effects, 

is 2 mg F-/L. 
19

Our search of the literature pertaining to fluorosis in 

animals yielded similar results. We were not able to find 

any reports of toxic effects in livestock or wildlife that 

occurred at lower F

-

 dosages than cause osteo-dental 

fluorosis. Thus, as a practical matter, maximum tolerable 

concentrations of F

-

 in water for livestock and wildlife 

should be based upon dental and osteal effects.

The effects of F in feedstuffs and water are additive; what 

really counts is the total dose of biologically available F

-

ingested by the animal. Most of the reports we reviewed, 

when reduced to mg F

-

/kg BW, indicate the threshold 

dose for chronic osteo-dental fluorosis in cattle is ap-

proximately 1 mg F

-

/kg BW. This is in agreement with 

the NRC,147 which indicates 30-40 ppm dietary F

-

 (which 

translates to 0.75-1.0 mg F

-

/kg BW) is the tolerance level 

for the more sensitive (i.e. during dental development) 

classes of cattle. 

Numerous studies have demonstrated the susceptibility of 

wild ungulates (deer, elk, etc.) to fluorosis; however, there 

has been only one controlled experiment211 from which 

dose-response can be extrapolated. A few other epide-

miologic studies provide sufficient data to form rough 

estimates of the amount of F

-

 required to produce signs of 

fluorosis in cervids. Taken together, these indicate wild 

cervids are approximately as sensitive to the toxic effects 

of F

-

 as cattle. Sheep seem to be slightly less sensitive 

than cattle although one Australian report indicated longterm exposure to as little as 10 mg F-

/L drinking water 

in Queensland decreased wool production.202 Given 

temperatures in that region, water consumption probably 

resulted in 1-2 mg F

-

/kg BW for much of the year. The 

sole report that included any data on horses suggested 

horses are two-fold more tolerant than cattle, but it goes 

on to describe situations in which ruminants and horses, 

sharing a pasture and water supply, were similarly affected. 

Assuming Wyoming forages normally contain less than 

10 ppm F-213, a water concentration of 3.75 mg F

-

/L 

would be required to achieve the 1 mg F/kg BW neces-

sary to cause fluorosis in cattle, and water containing less 

should not cause measurable production problems. 

We recommend water for cattle contain less than 2.0 

mg/L F-. By extension, these waters should also be safe 

for sheep, cervids, and probably horses.
20
21

Molybdenum (Mo), an essential trace element required 

for nitrogen fixation and the reduction of nitrate to 

nitrite in plants and bacteria, is widely distributed in 

nature.214 Geochemical surveys in England found that 

Mo content in soil and sediment corresponds closely 

to underlying black shales.215 Other sources of Mo in 

the environment include industrial contamination by 

metal alloy manufacturing, copper mining, and coal 

mining.216-221 Molybdenum occurs predominately as 

the molybdate (MoO4

2-) ion in natural water sources, 

and concentrations are typically very low (<2-3 μg/L), 

unless contaminated by an outside source, in which case 

they can reach 25 mg Mo/L.222,223 In forage, Mo concentrations vary and depend on the Mo concentration, 

moisture content, and the pH of the soil.222,224 Alkaline 

environments greatly increase the bioavailability of Mo to 

plants, and thus increase the likelihood of Mo toxicity in 

grazing animals.222,225 Surveys have identified extensive 

areas of forage containing potentially toxic concentrations 

of Mo (10-20 ppm) in at least five western states, including Wyoming.226 

Essentiality

Mo is an essential element for mammals due to its 

involvement in the enzymes aldehyde oxidase, sulfite 

oxidase, and xanthine oxidase.214,227 As a cofactor for 

these enzymes, it aids in catalyzing the oxidation or 

metabolism of sulfur-containing amino acids, purines, 

pyrimidines, and aldehydes.214 Experimentally, dietary 

Mo deficiency decreased feed consumption and caused 

a 25% reduction in live-weight gains in adult goats, 

and kids from deficient dams gained less compared to 

control animals.228,229 Reproductive effects of deficiency 

include decreased pregnancy rates and higher mortality 

in offspring.227-229 Dietary requirements are so low (about 

100 ppb DM), however, that deficiency is very rare under 

natural conditions.227

Metabolism

Once ingested, Mo is absorbed in the stomach and 

throughout the small intestine. In the small intestine, 

MoO4 is actively transported across the mucosal epithe5 Molybdenum

lium via the same carrier-mediated transport mechanism 

that transports sulfate (SO4).230 The administration of 

SO4 to monogastric animals consuming a Mo-rich diet decreases blood Mo concentration and increases excretion, 

potentially alleviating toxicity.230-234 Interestingly, dietary 

S increases the toxicity of Mo in ruminants, presumably 

as a result of thiomolybdate formation in the rumen. 

Molybdenum is transported in the blood as MoO4, where 

it is distributed to tissues for integration into enzyme 

systems. Excretion is primarily via urine; however, feces 

and milk can also serve as important routes of removal.214,235-238 The rate of absorption differs amongst species, 

age groups, and sex. For example, after orally administering Mo to swine and cattle, it was found that Mo peaked 

in the blood of swine after two to four hours, while it 

took 96 hours to peak in cattle.236 Water soluble forms 

of Mo, such as ammonium molybdate ((NH4)

6

Mo7O24), 

sodium molybdate (Na2MoO4), and Mo from forage, are 

more readily absorbed than their organic counterparts.214 

The ruminal interaction between Mo, SO4, and Cu is 

responsible for the greater sensitivity of ruminants than 

monogastrics to Mo. In the rumen, sulfur compounds 

(mostly SO4) are reduced to sulfide by rumen microbes. 

Sulfide then combines with MoO4 to form either tri- or 

tetrathiomolybdates (TM).214,239,240 Thus, in ruminants, 

relatively little MoO4 or S reach the small intestine to be 

absorbed as such. In the rumen, TMs bind irreversibly 

to the solid phase of digesta and act as powerful chelators 

of Cu, retaining it in the gut. As a result, Cu absorption from the GI tract is decreased as much as 88%.241-245 

Trithiomolybdates can also enter the circulation241,246

where they bind cooperatively with Cu to albumin, 

resulting in decreased availability of Cu for critical functions. Because this complex is insoluble in trichloroacetic 

acid (TCA), the term “TCA-soluble” Cu is often used 

as a synonym for biologically useful Cu.241,245,247-249 As a 

consequence of the binding to albumin, biliary excretion 

of Cu is enhanced, less Cu is incorporated into enzymes 

such as ceruloplasmin (Cp), and less Cu is stored in 

tissues. The decreased availability of Cu for enzyme 

synthesis impacts a number of physiologic processes, 

including immune function and bone and elastin formation.242,245,250-261 Trithiomolybdates bound to albumin are 
22

relatively stable; however, once unbound, TMs are rapidly 

hydrolyzed to MoO4 and SO4.

246,249,262

Since the clinical effects of molybdenosis are in large part 

due to secondary Cu deficiency, it is useful to review Cu 

metabolism. Although Cu is an essential trace element 

for all mammals and deficiency is frequently associated 

with a number of maladies, the Cu ion itself is quite 

toxic to cells. Thus, the metabolism of Cu in mammals 

involves a number of different carrier and storage proteins that bind Cu, permitting it to be absorbed, distributed, and eliminated without exposing cells to excessive 

amounts of the free ion. Copper is absorbed in the 

intestine by carrier proteins and stored in mucosal cells as 

a protein complex.263 In monogastric species such as rats, 

horses, and swine, most uptake occurs in the small intestine. In ruminants, there is some evidence significant 

absorption also occurs in the large intestine.245 Copper is 

transported to the liver bound to albumin and transcuprein, where the proteins and their bound Cu atoms are 

taken up into hepatocytes.263 Within the liver cells, Cu 

is distributed between various storage proteins, especially 

metallothionein (MT), microsomes, nuclei, lysosomes, 

and the cytosol.245,263 Copper is exported from the liver 

to the rest of the body for incorporation into enzymes as 

a protein complex with Cp.

Toxicity

Despite the fact Mo is intrinsically (i.e. without metabolism to TM) toxic245,264,265, secondary Cu deficiency is the 

most common pathogenesis underlying molybdenosis. 

The form of Mo ingested and, more importantly, the 

Cu:Mo ratio are critical determinants of toxicity.266-268 

Cu:Mo ratios of 2:1 or less result in clinical signs, and effects are exacerbated by high dietary S.267 Various authorities have recommended Cu:Mo ratios of 4:1 or greater 

as the minimum “safe” ratio.214,267,269 Signs of acute Mo 

toxicity include gastrointestinal irritation, diarrhea, liver 

and kidney damage, and, ultimately, death.253,267,270 Diarrhea appears to be a direct effect of Mo on the intestinal 

mucosal cells, rather than Cu deficiency.245 In chronic 

poisoning, anorexia and weight loss are initial clinical 

signs, followed by diarrhea, anemia, depigmentation of 

the hair coat (achromotrichia), ataxia, and bone and joint 

deformities.214,267,271,272 Integumentary lesions and bone 

and joint deformities are probably due to deficiencies of 

several Cu-dependent, critical enzymes, as well as possibly decreased P in bone.267,273,274 Decreased reproductive 

function, including decreased libido and fertility, has also 

been associated with molybdenosis.266,275-278

Acute to subacute toxicity has been demonstrated experimentally and occurs naturally in cattle, buffalo, and mule 

deer. The accidental addition of Na2MoO4 at the rate of 

19,000 ppm (estimated Mo concentration 7,400 ppm) to 

cattle rations resulted in decreased feed intake, hind limb 

ataxia, profuse salivation and ocular discharge, diarrhea, 

liver and kidney damage, rough hair coat, and death.270 

Feeding 1.36 g Mo per head per day to five cows for an 

unspecified amount of time produced extreme scouring 

and loss of condition in three animals.279 After consuming a ration containing 10.5 ppm Cu and 140 ppm Mo 

for three to four days, Holstein-Friesian lactating cows 

and steers developed hemorrhagic diarrhea and front 

limb lameness, and they died.280 Contaminated grazing 

pastures with forage Mo concentrations between 16-24 

ppm and 6-11 ppm Cu resulted in acute diarrhea, loss 

of condition, and posterior stiffness in cattle.221 Feeding 

2,000 ppm Mo as (NH4)

6

Mo7O24 for three days resulted 

in diarrhea and feed refusal in cattle.281 After grazing a 

pasture contaminated with used motor oil containing 

molybdenum bisulfide for two weeks, cattle exhibited 

diarrhea, anemia, decreased milk production, achromotrichia, and hind limb weakness.282 Four male buffalo were 

given 5 mg Na2MoO4 (2.35 mg Mo)/kg BW/day for 

180 days; by two weeks, clinical signs included diarrhea, 

decreased weight gains, incoordination, swelling of hind 

fetlocks, and irregular hoof wear.283 Including 2,500 ppm 

Mo as Na2MoO4 (equivalent to approximately 62.5 mg 

Mo/kg BW) or more in the diets of mule deer for 33 days 

resulted in diarrhea and feed refusal; whereas, smaller 

doses were without apparent effect. The authors concluded that deer are relatively resistant to Mo, compared 

to cattle.284

Relatively few studies of molybdenosis have been conducted in monogastrics. Most of these involve relatively 

large doses of Mo and don’t seem to involve Mo-Cu-S 

interactions.233,285-288 Rats given a diet containing 1,000 

mg Na2MoO4/kg BW for five weeks gained significantly 

less than controls, and 50% developed mandibular exostoses.289 Feeding rats 1,200 ppm Mo as Na2

MoO4 for six 

weeks resulted in decreased weight gains, and skin, tail 

rings, and femurs all required much less force to break 

compared to control tissues.290 Six hundred ppm Mo 

fed to rats for three weeks caused a depression in nutrient utilization and decrease in gain.286 Rats consuming 

800 ppm Mo for five weeks showed a 36% depression in 

growth; adding 0.29% SO4 largely prevented this effect.233 Male rats given 1,200 ppm Mo as Na2

MoO4 for 

four to five weeks showed a 53% reduction in growth as 
23

well as reduced feed intake, followed by death.285 One 

thousand ppm dietary Na2MoO4 resulted in weight loss, 

diarrhea, hair changes, palpable mandibular nodules, and 

other bone and joint abnormalities in rats.291 Rats fed 

20 ppm Mo and 5 ppm Cu showed significant reduction 

in gains and depigmentation of hair.275 Rabbits consuming 1,000 ppm Mo as Na2

MoO4 in a diet with 16.4 

ppm Cu developed anorexia, alopecia, slight dermatosis, 

and anemia, and they died after four weeks.273 Feeding 

rabbits 4,000 ppm Na2MoO4 (roughly 55 mg Mo/kg 

BW) for four weeks resulted in anemia, abnormal bone 

development, and degeneration of myocardium and 

skeletal muscles.292 Ponies fed up to 102 ppm Mo with 

normal (9 ppm) dietary Cu remained asymptomatic for 

50 days.293 Similar results were reported in colts fed 50 

ppm dietary Mo.287 Four horses fed 20 ppm dietary Mo 

as 99Mo did not exhibit any signs of molybdenosis or deranged Cu metabolism. The radioactive label in plasma 

was bound to the MoO4 ion rather than TM, as seen in 

ruminants.288

Chronic toxicity has been investigated both in field studies and experimentally in cattle, sheep, and ruminant 

wildlife. Forage containing 24-28 ppm Cu and 14-126 

ppm Mo that had been contaminated by a metal alloy 

manufacturing plant resulted in emaciation and diarrhea 

in cattle beginning four weeks after introduction to the 

affected pasture.219 Cattle grazing pasture contaminated 

by aluminum alloy plants at a concentration of 77.5 ppm 

Mo exhibited severe scouring, loss of condition, decreased 

milk production, and achromotrichia.220 Cattle grazing 

pastures containing 1-20 ppm Mo exhibited diarrhea, 

listlessness, and abnormal hair color compared to animals 

grazing pastures containing < 1 ppm Mo with no clinical signs.218 Feeding two male calves, with average body 

weights of 460 pounds, 4.0 g Na2MoO4/day resulted 

in diarrhea, discolored hair, weight loss, anemia, and 

decreased libido.266 Cattle consuming a diet containing 

4 ppm Cu and 5 ppm Mo exhibited decreased weight 

gains, decreased feed intake, and abnormal hair texture 

and color after 16-20 weeks.264 Pastures containing 25.6 

ppm Mo produced severe diarrhea, emaciation, anemia, faded hair color, salt craving, and death in grazing 

cattle.294 Yearling steers given 1.5 mg Mo/kg BW for 150 

days and grazed on pasture containing 0.32% S developed diarrhea, inflammation of the sheath, rough hair 

coat, and anemia.295

Grazing forage containing 4-14 ppm Cu and 95-460 

ppm Mo and drinking water with 14 μg Cu/L and 7,200 

μg Mo/L for 11 weeks resulted in watery diarrhea, rough 

hair coats, and a stiff shuffling gait in 50% of cow-calf 

pairs.296 Forage contaminated with 2-220 ppm Mo 

caused diarrhea, roughening and discoloration of the 

hair coat, and weight loss in grazing cattle.297 Forage 

concentrations of 16.5-23.5 ppm Mo and 2-25 ppm Cu 

resulted in diarrhea, weight loss, and achromotrichia in 

cattle.298 Feeding 100 ppm Mo to heifers for 11 months 

resulted in anemia, scouring, achromotrichia, and weight 

loss. Five of 16 died two weeks after termination of the 

experiment.299 Heifers receiving diets containing 100 

ppm Mo and 0.3% S as SO4 became emaciated and 

diarrheic after one month at this treatment level. Heifers 

given 5-20 ppm Mo with 0.3% S or 50 ppm Mo without added S did not exhibit any signs of illness, but they 

did have decreased tissue Cu compared to controls.300 

Weight loss and scouring were evident in cows ingesting 173 ppm Mo for two months. Diets containing 

53 and 100 ppm Mo did not produce clinical signs but 

did interfere with Cu metabolism.301 Forage containing 

6-36 ppm Mo resulted in emaciation in cattle with severe 

diarrhea, anemia, achromotrichia, and swollen genitals.302 

Water containing 50 ppm Mo induced signs of secondary Cu deficiency in five-week-old calves.303 Moose in 

Sweden have been reported to exhibit signs of molybdenosis similar to cattle, including diarrhea, emaciation, 

achromotrichia, sudden heart failure, and osteoporosis; 

however, no levels of Mo in the forage or water sources 

were reported.304

Sheep grazing pastures containing 5.5-33.5 ppm Mo 

and 6.0-8.7 ppm Cu for 76 weeks developed hemorrhaging around the femoral heads, tuber sacrales, and 

psoas muscles. Exostoses were frequent on humeri and 

femurs, and the periosteum appeared to have lifted from 

the bone surface.225 Feeding ewes 1 kg commercial grass 

cubes with 5 ppm Cu and supplemented with Na2SO4

and (NH4)

6

Mo7O24 to provide 10 g SO4 and 50 mg Mo, 

respectively, until one month prior to lambing resulted 

in incoordination of front and hind limbs and a marked 

ataxia in lambs within 60 days of birth.305 Sheep grazing 

pastures with 20 ppm Mo and 5-7 ppm Cu developed 

connective tissue lesions including lifting of the periosteum and hemorrhaging in periosteum and muscle insertions.306 Drenching (i.e. dosing by stomach tube) goats 

daily with (NH4)

6

Mo7O24 to provide 50 ppm dietary Mo 

for 235 days caused general debility, depigmentation of 

hair coat, and weight loss.307

Notwithstanding other work, several studies have failed 

to produce any adverse health effects after Mo ingestion. 

Grazing cattle on pastures containing 13 ppm Mo and 
24

supplementing with 17 ppm Cu for six months resulted 

in no signs of adverse effects.308 Cattle grazing a reclaimed mine tailing site containing 21-44 ppm Mo and 

13-19 ppm Cu for three consecutive summers exhibited 

no signs of Mo toxicity.217,309,310 No adverse effects were 

noticed in a cannulated steer consuming sun-cured hay 

containing 49.68 ppm Mo and 19.09 ppm Cu.311 In 

each of these studies, low S in both the diet and water 

was offered as being a possible explanation for the lack of 

clinical signs observed. 

Summary

Horses, like most monogastric animals, are very resistant 

to the effects of Mo as compared to ruminants. Cattle are 

commonly cited as slightly more susceptible to molybdenosis than sheep, and limited quantitative data suggest mule deer are relatively resistant compared to cattle. 

Therefore, drinking water Mo concentrations that are safe 

for cattle are probably also safe for horses, other classes 

of livestock, and wild cervids. Although there is quite a 

bit of variability in the reports summarized above, and 

some (large) amount of dietary Mo may cause poisoning 

regardless of Cu status, the bottom line seems to be that 

total dietary Cu:Mo ratios of less than 2-4 can result in 

chronic toxicity and decreased production in cattle, especially if dietary S is higher than absolutely necessary. 

As with many substances, the effects of forage and water 

Mo concentrations are additive, and, in some areas of the 

western United States, forage Mo concentrations are already toxic or very nearly toxic. Under these conditions, 

any additional Mo intake contributed by drinking water 

is potentially dangerous. In these areas, however, producers are likely already aware of the problem and feeding supplemental Cu. A more normal situation would 

be cattle grazing “typical” Wyoming forage containing 7 

ppm Cu (or supplemented to that level) and negligible 

Mo (~1 ppm). Under these conditions the critical safe 

4:1 ratio would be exceeded whenever drinking water 

contains 375 μg Mo/L. 

We recommend that, in the absence of other data, 

drinking water for livestock and wildlife contain 

less than 0.3 mg/L. If dietary Mo is higher, which is 

not unusual in this region, water Mo concentrations 

should be adjusted downward accordingly.
25

The nitrate (NO3

-

) and nitrite (NO2

-

) ions are intermediates in the biological nitrification cycle and the primary 

source of nitrogen (N) for plants in the soil. Plants accumulate NO3

-

 from soil to synthesize protein via a multistep process; excessive NO3

-

 accumulation as a result of 

this process may cause poisoning of grazing animals.312 

Nitrate or NO2

-

 may contaminate water as a result of 

contact with natural minerals (e.g. niter), agricultural 

runoff (fertilizer, manure) or industrial processes.312-314 

Nitrate is the more stable of the two N species and therefore more common in surface waters.315 Nitrite (NO2

-

) 

usually results from biological reduction of NO3

-

, but it 

may also be an industrial contaminant or exist in ground 

waters where pH and redox potential prevent oxidation 

to NO3

- 

.

315 Both ions are extremely water-soluble and 

therefore water-mobile.

Essentiality

Although N is an essential macro element for mammals, 

NO2 and NO3 are not essential per se.

Metabolism

While the NO3

-

 ion is readily absorbed in the upper gastrointestinal (GI) tract and possesses intrinsic toxicologic 

properties such as vasodilation, the condition referred to 

as “nitrate poisoning” actually depends upon reduction of 

NO3

-

 to NO2

-

 in the upper GI tract.312,316-318 This process 

occurs in human infants319,320, and it is the basis of current human drinking water standards, but nitrate toxicity 

is primarily a problem in ruminant species, as the rumen 

microflora are well-suited to catalyze NO3

-

 reduction. 

Radiotracer studies indicate that NO2

-

, formed from 

NO3

-

 in the rumen, may either be further reduced and 

incorporated via NH3 into amino acids or reduced via 

nitric oxide to N and expelled.321 Unfortunately, neither 

of the latter pathways (i.e. amino acids or N) is as fast as 

the initial reduction to NO2

-

, and dangerous NO2

-

 concentrations accumulate in the GI tract when assimilatory 

pathways are overloaded.321-323 Under the proper dietary 

conditions (mainly adequate carbohydrates) the assimilatory pathways can adapt to high NO3

-

 concentrations, 

and very little NO3

-

 or NO2

-

 escape the rumen.314,322,324-327 

Sustained exposure to moderately high NO3 diets results 

in induction of the assimilatory pathways, and this ability 

may be acquired by transfer of GI flora from one ruminant to another.322,323 Once absorbed into the bloodstream, the NO3

-

 ion is rapidly distributed throughout 

the body water and excreted via urine and saliva, whereas 

the NO2

-

 ion is oxidized to NO3

-

 via a coupled reaction 

with hemoglobin and eliminated as NO3

-

.

316,318,328,329 

Other differences between ruminants and monogastrics 

in the metabolism of the NO2

-

 and NO3

-

 ions, while 

not directly tied to the ruminal metabolism of NO3

-

, 

probably reflect evolutionary pressure of the constant 

background of NO2

-

 ruminants receive from ruminal 

metabolism. The blood t1/2 of NO2

-

 is similar in monogastrics and ruminants, but the elimination of NO3

-

 from 

blood is much slower in monogastrics316 and the normal 

background metHb concentration is higher in monogastrics.330 In ruminants only a small portion of an oral dose 

of NO3 is eliminated in the urine, whereas in monogastrics most ingested NO3

 is eliminated via urine.314

Some sources suggest the NO3

-

 ion is more bioavailable 

in water than feedstuffs.312-314 The experiments this 

conclusion was drawn from, however, were based upon 

aqueous NO3

-

 administered directly into the stomach vs. 

contaminated feedstuffs offered ad libitum.314 The most 

important determinant of NO3 toxicity seems to be how 

rapidly a given dose of NO3

-

 is administered, rather than 

whether it is in feed or water.314,331,332 For example, the 

single oral median lethal dose (SOLD50) of NaNO3 in 

cows was reported to be 328 mg/kg BW when given at 

once, but when the same dose was spread over 24 hours, 

the LD50 increased to 707-991 mg/kg.331 

Toxicity

Although the most common source of NO3 poisoning in 

livestock is contaminated feedstuffs, NO3

-

-contaminated 

drinking water has poisoned people and animals.320,333-336 

The mechanism of poisoning involves GI microbial 

reduction of the NO3

-

 ion to NO2

-

, which is absorbed 

into the bloodstream where it oxidizes the ferrous iron 

atoms (Fe+2) in hemoglobin (Hb) to the ferric (Fe+3) 

state, resulting in methemoglobin (metHb), which can6 Nitrate and Nitrite
26

not transport oxygen from the lungs to the rest of the 

body. The exact mechanism by which Hb is oxidized is 

the subject of some controversy but is currently thought 

to be a multi-step autocatalytic process involving several 

free radicals.328 The end product of this reaction is NO3

-

, 

which is eliminated via urine and saliva. As might be 

expected, the clinical signs of acute NO3 poisoning (cyanosis, hyperpnea, muscle tremor, weakness, collapse, and 

death) reflect the effects of anoxia on critical organs such 

as the brain and heart. Pregnant animals that survive 

episodes of acute NO3 poisoning during the latter part 

of pregnancy may abort within one to two weeks.333,337-340 

Poisoning during earlier pregnancy does not usually result 

in abortion.313,331,333,341

As might be expected from the toxic mechanism, monogastric animals (with the exception of human infants) 

seem to be relatively resistant to the effects of NO3

compared to ruminants. Textbooks suggest NO3 is 

approximately 10-fold more toxic in ruminants than 

monogastric animals.317 Burwash et al.342 fed six mares 

high NO3 (1.7-1.85%) oat hay for 13 days. Although 

the serum NO3

-

 concentration increased significantly, 

there was no change in metHb concentration, no effects 

on blood chemistry parameters, and no clinical signs of 

poisoning. They concluded it is safe to feed horses diets 

containing 2% NO3 and “likely much higher” concentrations. Mice exposed to drinking water containing 1,000 

mg NO3

-

/L for 18 months excreted more ammonium 

ion than controls early in the study and may have died 

slightly sooner (17.5 months vs. 18 months) but did not 

show any signs of poisoning.343 Seerley et al.344 fed water 

containing 1,465, 2,900, or 4,400 mg NO3

-

/L as NaNO3

to weanling pigs for 84 days with no effect upon rate of 

gain, water consumption, or clinical signs of toxicity. The 

difference in toxicity between animal species is not nearly 

as pronounced for NO2.

317 Although rare, monogastric 

animals have been acutely poisoned by the NO2

-

 ion from 

water335 and feedstuffs.345

Wright and Davison346 reviewed the literature and 

concluded the LD50 of NO3 in ruminants was between 

700-985 mg NO3/kg BW when fed as dry feed. Experimentally, sheep have been acutely poisoned by NO3

 doses 

as low as 300 mg/kg BW323,325,329,347; however, doses as 

large as 800 mg/kg BW have been fed without measurable effects.323,326,327,340,347,348 Field reports have incriminated feedstuffs containing as little as 2% ppm dietary 

NO3 (which would provide about 500 mg NO3/kg BW) 

as causing acute lethality in sheep .349,350 Experimentally, 3.4% dietary NO3

, fed as pigweed or oat hay killed 

two of five ewes. The lethal dosages, calculated from 

consumption data, were 660 and 730 mg NO3/kg BW, 

respectively. Campagnolo et al.351 reported the accidental 

poisoning of several animals, including sheep, by water 

containing 6,000 mg NO3

-

/L at a county fair; however, 

the water contained several other substances that might 

also have been toxic. 

Cattle have been experimentally poisoned by 520 mg/kg 

BW or more NO3 incorporated into feedstuffs341,346,352,353, 

and as little as 200 mg/kg BW may be toxic if given 

by gavage.354 Several investigators324,354,355 consistently 

produced sublethal toxicity with 200-300 mg NO3/kg 

BW in order to test various protective strategies. Other 

investigators322,356,357 failed to demonstrate toxicity at dietary concentrations as high as 0.9% (approximately 225 

mg NO3/kg BW), although one322 reported that sustained 

exposure enhanced the ability of the rumen microflora 

to degrade NO3

-

 and NO2

-

. Calves were experimentally 

poisoned by drinking water containing 2,500 mg NO3

-

/L (250 mg/kg BW), but none were affected by 2,000 

or less.338 Older texts and reviews variously describe the 

minimum toxic dose in cattle as 169-500 mg NO3/kg 

BW.313,317,358

There are numerous anecdotal reports of acute NO3

poisoning in cattle associated with contaminated feedstuffs. O’Hara and Fraser359 summarized 10 episodes of 

acute NO3 poisoning in New Zealand in which mortality 

varied from less than 1% to almost 50%. Forage concentrations associated with these cases ranged from 0.3-5.3% 

NO3 (mean = 3.3%) with variations of 1-2% NO3 between samples from the same premise. In one extensively 

investigated case, 23 of 50 calves turned into a ryegrass 

pasture containing 6.6-8.9% KNO3 (4-5.3% NO3) died 

within a 12-hour period.359 In another instance, calves 

died if left on a ryegrass pasture containing 3.6% NO3

for more than one hour.360 A dose of NO3, later calculated to be 170 mg NO3

/kg BW, from contaminated 

hay killed seven of 200 heifers. The herdsman tried 

to dilute the toxic hay in half and killed seven more.361

The authors speculated that concurrent overfeeding of 

monensin enhanced ruminal reduction of NO3

-

 to NO2

-

, 

thus potentiating the toxicity of the hay. Harris and 

Rhodes362, summarizing the experience of farmers during 

a severe drought in Victoria, Australia, reported several 

hundred animals were killed by plants containing “over 

1.5% NO3.” Three cows fed hay containing 1% NO3

died within 30 minutes.353 Eleven cows aborted, and 73 

of 153 died when fed sudax hay containing 1.1-3.1% 

NO3.

363 McKenzie summarized several cases with acute 
27

mortalities of 16-44% on button grass (2.4-7.2% NO3) 

grown in N-rich soil in Queensland, Australia.349 Animals grazing the same grass in adjacent paddocks without 

the extra N were unaffected.

Although not as common as poisoning from feedstuffs, 

contaminated water has resulted in acute poisoning, 

including abortions and death. Seven of 12 cows died 

shortly after drinking water containing 2,790 mg NO3

-

/L.336 Several authors reported lethality as a result of 

fertilizer-contaminated water ( 1,000-6,000 mg NO3

-

/L).333,351,364 Contaminated liquid whey, fed in addition 

to water and containing 2,200-2,800 mg NO3

-

/L, killed 

17 of 360 cattle. Whey containing only 400-800 mg 

NO3

-

/L did not kill any animals, but it did result in 26 

of 140 cows aborting.333 Yong et al.334 reported that water, contaminated with 4,800 and 7,000 mg NO3

-

/L as a 

result of blasting water holes, killed 16 of 100 and four 

of 90 cows in two separate incidents in Saskatchewan, 

Canada.

It is known the NO2

-

 ion may react with secondary 

amines (common in many foodstuffs) under conditions typical of the adult human stomach (pH 1-4) to 

form nitrosamines.365-367 Many nitrosamines are potent 

animal mutagens and carcinogens. Bacterial reduction 

of NO3

-

 to NO2

-

 does not occur under the acid conditions necessary for nitrosamine production, or vice versa, 

but it is theoretically possible NO2

-

 excreted in saliva 

or ingested in water might cause cancer in people. In 

practice, however, salivary secretion contributes much less 

NO2

-

 than other sources such as vegetables, and attempts 

to link nitrosation, mutagenesis, and/or cancer with 

drinking water NO3 consumption have been negative 

or only equivocal.365-371 This, together with the fact most 

herbivores have GI conditions that are even less prone 

to nitrosamine formation than humans, suggests cancer 

is not a likely sequella of NO3 exposure in our species of 

interest. Elevated NO2 is a potential acutely toxic hazard, 

however. Four of four sows were killed by drinking 

1,940 mg NO2/L water.335 Nitrite is reported to be 2.5 

times more toxic than NO3 in ruminants and 10 times 

more in monogastrics317, and the minimum toxic dose is 

reportedly between 20-90 mg NO2/kg BW in pigs and 

90-170 mg NO2/kg in cattle and sheep.313,358 

Chronic NO3 poisoning is another area of controversy. 

Mice exposed to 1,000 mg NO3

-

/L in drinking water for 

18 months (life time) died prematurely starting at 17.5 

months. The result was of only marginal statistical significance, and no possible mechanism for the result was 

proposed.343 Mice exposed to 100 mg NO3

-

/L showed no 

effects in any parameter measured (liver function, kidney 

function, serum protein, etc.). Seerley et al.344 fed breed- fed breeding gilts NaNO3

 in water to provide 1,320 mg NO3

-

/L 

for 105 days with no effect. Similar results were reported 

for weanling pigs.372,373 Fan et al.374 reviewed the veterinary literature on chronic NO3

 toxicity and concluded it 

“failed to provide evidence for teratogenic effects attributable to NO3

 or NO2 ingestion.” A retrospective epidemiologic study of pregnant women in the Mt. Gambler 

region of Australia indicated a “statistically significant 

increase in risk of bearing a malformed child” in women 

who drank water with more than 66 mg NO3

-

/L, but it 

did not take into account other factors associated with 

the water wells. Bruning-Fann et al.375 surveyed water 

from 712 swine operations in the United States and 

found no differences in litter size or piglet mortality attributable to well-water containing NO3

-

 (1-443 mg/L).

After a widespread drought in the American Midwest in 

the mid-1950’s, several authors summarized the experience of multiple field investigations.376-378 Purportedly, 

feed concentrations greater than 0.5% NO3 or water 

supplies containing more than 500 mg NO3

-

/L were 

hazardous to cattle fed “poor quality” rations. Case377

was first to propose that NO3 interfered with vitamin A 

metabolism. The results of many controlled experiments 

since then have rendered this theory “questionable”.312 

Sheep fed 2.5% NaNO3 (approximately 1.75% NO3) 

diets for 135 days had slightly lower liver vitamin A 

concentrations than controls, and gains were depressed. 

A second replicate of the same experiment did not exhibit 

decreased vitamin A nor was there an increase in metHb 

or signs of toxicity in either group.348 Fourteen yearling 

steers were divided into seven groups and treated with 

various combinations of NO3

-

 in drinking water, NO2

-

in drinking water, E. coli, and a “thyroid depressant.” 

Creative use of statistics demonstrated depressed carotene 

utilization, but there were no other effects.379 On the 

other hand, heifers fed various amounts of NO3 up to 

0.9% NO3 in diets containing 20% or 40% concentrate 

did not exhibit any difference from controls in carotene 

conversion or hepatic retinol concentrations.356 Feedlot 

cattle fed 0.81% dietary NO3 as NaNO3 exhibited poor 

gains as a result of decreased feed consumption. Gains 

were not improved by supplementing with 12,000 IU 

vitamin A.357 Emerick380 reviewed the literature and concluded that chronic effects involving vitamin A, thyroid 

function, and other hypothetical chronic mechanisms 

only occurred at doses that were nearly toxic due to 

metHb formation.
28

Winter and Hokanson381 fed varying amounts of NO3

(330-690 mg/kg BW) to dairy heifers as part of their ration to maintain metHb levels at either 25-30% or 50% 

for the last six months of pregnancy. One animal aborted, possibly as a result of NO3

 intoxication and two died 

of acute poisoning after a diet change, but no chronic 

effects could be ascertained. Crowley et al.332 in what, to 

date, has been the most rigorous experimental attempt to 

produce chronic NO3 poisoning in dairy cattle, fed high 

NO3

-

 water (384 mg NO3

-

/L) for 35 months with no effects on conception rate, twinning, stillbirths, abortions, 

retained placenta, or a variety of production parameters. 

The only statistically significant effect was a slightly lower 

first-service conception rate in the NO3 group. The 

authors concluded that, in a herd fed a balanced ration, 

“water containing up to 400 ppm NO3 should not cause 

any serious problems.”332 Ensley382 attempted an epidemiologic approach to the question of high NO3

 water 

for dairy cattle. In a survey of 128 Iowa dairies with 

water concentrations from 1-300 mg NO3

-

/L, he found 

water NO3 concentrations were positively correlated with 

services per conception, which agrees with the results of 

Crowley et al., but several other potentially confounding 

factors such as the size of the farm and other contaminants in the water were also positively correlated with 

NO3 concentrations. 

Other attempts to produce chronic NO3 poisoning in 

ruminants have been unsuccessful. Sinclair and Jones327

dosed ewes with 15 g KNO3 (similar to 1.5% in forage) 

for two months and then sprayed the same dose of NO3

on the daily hay ration for another seven weeks. Ewes 

were fed diets containing 0.2-2.6% NO3 as NaNO3 or 

from natural sources for 12 weeks with no effects on 

health or pregnancy.340 Despite elevated serum NO3

-

 concentrations, there were no effects on metHb, body condition, or reproduction in the treated group. Whethers 

fed NaNO3 in drinking water to provide 1,465, 2,900, 

or 4,400 mg NO3

-

/L for 84 days did not differ from 

controls in gain and water consumption, and only modest increases in metHb concentrations were seen at the 

highest dose.344 Feeder lambs fed 3.2% dietary KNO3

(1.9% NO3) until slaughter differed from controls only 

in “carcass quality326.” Emerick380 reviewed the literature 

in 1974 and concluded that feeds containing less than 

0.44% NO3 and water with less than 440 mg NO3

-

/L 

were “well within a safe range for all classes of livestock.”

Summary

There is no question NO3 contamination of drinking 

water can result in acute death and/or abortion in ruminant livestock. Cattle are usually reported to be more 

susceptible than sheep, with monogastrics such as horses 

and swine being relatively resistant. Surprisingly, we were 

able to find only one report of NO3 poisoning (from 

feedstuffs) in wild ruminants383, but, given the physiological similarities with domestic animals, it is reasonable to 

assume deer, antelope, and elk are also susceptible. 

The chronic toxicity of very low doses of NO3 is controversial. Despite repeated attempts (and failures) to 

reproduce vitamin A deficiency, hypothyroidism, or other 

chronic forms of NO3 toxicity, experimentally it does not 

seem that dietary concentrations significantly less than 

those required for acute intoxication cause measurable 

ill-effects in domestic ruminants. While there is no ques here is no question NO3

 can produce abortions in ruminants, the dose 

required appears to be very near that required for acute 

toxicity. The most scientifically rigorous examination of 

chronic NO3 toxicity to date332 concluded that water concentrations less than 400 mg/L (the concentration tested) 

should not pose any hazard to a well-managed herd. 

The lowest toxic dose of NO3 in cattle in the experimental studies we reviewed is somewhat less than 200 mg 

NO3

-

/kg BW, although there were several experiments 

that failed to produce any effect at considerably higher (as 

much as 800 mg/kg BW) doses. Clinical (i.e. anecdotal) 

reports, in particular those of Yeruham et al.384 and Slenning et al.361, push the minimum toxic dose down to near 

100 mg NO3/kg BW. There are some uncertainties associated with these two reports. Yeruham did not specify 

the amount of toxic whey consumed (we assumed 20% 

BW when figuring a dose as it occurred in a hot climate), 

and there was a two-fold variation in analytical results 

between samples. Slenning et al. suggested other factors, 

notably overfeeding an ionophore, might have potentiated the toxicity of NO3

. The next lowest concentration 

reported to be acutely toxic was 1% NO3 in Chenopodium hay, which would provide approximately 250 mg 

NO3/kg BW in cattle under the assumptions outlined in 

the Introduction. Nitrate in water is additive with NO3

in feedstuffs, with a given dose in water being somewhat 

more potent than in feed because it is consumed more 

rapidly. 
29

Assuming negligible forage NO3 concentrations, a water NO3

 concentration of 500 mg NO3

-

/L (measured as 

NO3

- ion) would provide 100 mg/kg BW, which would 

provide a two-to-three fold margin below the 200-250 

mg/kg BW dose above. If forage concentrations are 

higher (not a rare occurrence in the Great Plains) the 

permissible water concentration should be adjusted 

downward.

The NO2

-

 ion is commonly described as approximately 

2.5-fold more toxic than the NO3

-

 ion in ruminants 

(10-fold more toxic in monogastrics), which implies a 

safe threshold of about 200 mg/L. We were, however, 

unable to find sufficient experimental studies or welldocumented field investigations upon which to base any 

conclusion about maximum safe concentrations. This 

is probably due to the fact NO3

-

 is the more stable form 

of the two in surface waters and feedstuffs, and NO2

-

 is 

only rarely present in negligible concentrations. Garner 

describes the minimum lethal dose of NO2 in swine (the 

most sensitive species) as 40 mg/kg BW358, which translates to 200 mg NO2

-

/L in drinking water under very 

conservative assumptions. Intravenous administration 

(the most potent route of exposure for most toxicants) of 

12 mg NO2

-

/kg BW to cattle and 17.6 mg NO2

-

/kg BW 

to sheep did not produce any reported toxic effects. 

Obviously, this is an area that needs further research, 

but we believe, based upon the existing knowledge base, 

100 mg NO2

-

/L (as the nitrite ion) should not cause 

poisoning in livestock.
30
31

 pH is defined as “the negative log of the hydrogen ion 

(H+) activity,” although “concentration” is often substituted for “activity” in a working definition.385 In other 

words, if the pH is 7.0, the H+ concentration ([H+]) is 

10-7 moles per L; if the pH is 3, the concentration is 10-3. 

Water with a pH below 7 is “acidic,” and water with a pH 

above 7 is “basic” or “alkaline.” The definition of “normal” water pH varies between authorities, but it is usually 

described as somewhere between 5.5-6.5 and 8-9. By 

comparison, vinegar is pH 3, colas are between 3-4, beer 

is between 4-5, and milk is around pH 6.4. A related 

measurement, alkalinity, is based upon the capacity of 

a water sample to resist a change in pH and is usually 

reported as mg/L of CaCO3. The pH controls solubility 

and concentrations of elements in water. For example, 

many metals precipitate out of alkaline water, whereas 

many dissolve in acidic water.

Water pH impacts the effectiveness of various water 

treatments and its palatability for animals. For example, 

the effectiveness of chlorination is reduced at a high pH. 

Low pH may precipitate or inactivate medications commonly delivered in drinking water. Sulfonamides are a 

particular concern in this respect as precipitated medication may leach back into the water after treatment has 

ended, contributing to potential drug residues in food 

animals. Acidic water tends to have a sour taste; basic is 

described as metallic. The taste threshold for hydrochloric 

acid is as low as 0.0001 mol/L.385 Acid water also tends 

to dissolve metals from plumbing and soil it contacts, 

further impacting palatability. 

Function

In the body, extracellular fluid (ECF) is normally maintained within a very narrow range centered around pH 

7.4.385,386 A number of critical physiological processes 

are pH-dependent, thus any significant departure from 

“normal” may be harmful to the organism.386

Metabolism

The acid-base balance in mammals represents a dynamic 

equilibrium between metabolic acid production and its 

elimination. As such, it is influenced by a number of 

7 pH

interdependent processes, especially respiration and urine 

production, chemical buffering by bone and other tissues, 

and several dietary elements. A comprehensive review of 

these processes is beyond the scope of this report, but, 

in brief, a decrease in plasma pH from normal (acidosis) 

stimulates increased respiration, decreasing the blood 

concentration of CO2 that would otherwise react with 

water to form carbonic acid (H2CO3). It also stimulates 

the kidney to produce urine that is more acidic. It does 

this by increasing elimination of the H+ ion. The net 

result is an active elimination of acid and an increase in 

plasma pH back towards normal.385,386 The H+ ion may 

also react chemically with buffering molecules in bone, 

minimizing the magnitude of any pH change.387,388 

Certain nutrients, referred to as “strong ions,” while not 

acidic or basic in the chemical sense, influence animals’ 

acid-base balance by shifting the equilibrium of internal 

homeostatic processes to enhance or inhibit the elimination of H+

 from the body. For example, diets rich in Na+

and K+ tend to “push” the body in the alkaline direction, 

whereas Cl-, as ammonium chloride (NH4Cl), is used 

clinically to move the balance in an acidic direction. 

Dairy nutritionists compound rations on the basis of the 

“strong ion difference” equation ((Na++K+)-(Cl-+S2-)).386

Diets with a negative strong ion difference produce mild 

acidosis shortly before lactation, which decreases the 

incidence of milk fever.389-391

Toxicity

Excessively acid or basic drinking water can theoretically 

affect animals in four ways. First, extremes of pH may 

result in tissue damage to the mouth and oropharynx, 

causing irritation and refusal to drink. Second, unusual extremes of pH may dissolve materials from pipes, 

ditches, etc., which are toxic or impart an unpleasant 

taste to the water. For example, Cu, Fe, and Pb concentrations have all been shown to increase in acidic water 

as a result of leaching the metals from plumbing.392-395

Consumption of acidic drinks may dissolve dental enamel 

and weaken teeth.396,397 Finally, consumption of a large 

amount of excessively acid or basic water could theoretically shift the body’s acid-base balance.
32

We were unable to find any reports detailing acute toxicity as a result of drinking extremely acid or basic water, 

although co-author Merl Raisbeck has investigated field 

cases in which cattle drank extremely basic solutions 

(pH 12-14) resulting in erosions and hemorrhage in the 

mouth and esophagus.

“Acid rain,” precipitation rendered acidic by atmospheric 

pollution, is a well-recognized problem in aquatic organisms because toxic elements, especially Al, are leached 

from solids that come in contact with the acidic water. 

It is especially problematic in poorly buffered surface 

waters of northeastern North America.398 Mammals are 

considerably less sensitive to the effects of dissolved metals than fish, but acidic water supplies have been suggested as contributing to the presence of Pb and Cu in 

domestic drinking water, a possible concern for human 

health.392,393,395 Even if not present at toxic concentrations, many elements impart a repellent taste to water.

Despite the hypothetical potential of acidic (pH < 5.5) 

water to cause acidosis in animals, water systems in 

laboratory animal colonies and, to a lesser extent, swine 

facilities, are commonly acidified to minimize bacterial 

infections.396,399-401 It is thought the acidified environment protects the intestinal epithelial barrier from bacterially-mediated disruption as well as reducing bacterial 

contamination in the water itself.399 

Some effects have been observed in ruminants and 

monogastrics due to the ingestion of acidic feed and 

water. Acidogenic rations are fed to dairy cattle during 

late pregnancy to prevent milk fever. For example, the 

addition of NH4Cl and ammonium sulfate ((NH4)

2

SO4) 

at 98 g apiece/head/day to the diet of lactating dairy cows 

lowered blood pH, increased blood calcium (Ca2+), and 

increased excretion of urinary Ca2+ and the ammonium 

ion (NH4

+

).390 The same amount of these salts added to 

drinking water would result in a pH of approximately 

5.5. Mineral acids (HCl and H2SO4) have been fed to 

prevent milk fever.402 Dairy cows given rations containing 0.65% or 1.8% hydrochloric acid (HCl) (equivalent 

to pH 2-3, respectively, if added to drinking water) had 

increased blood Ca2+, a small (0.05) decrease in blood 

pH, acidic urine, and a decreased incidence of milk 

fever.391 Rats given water acidified to pH 2.0 with HCl 

or H2SO4 for six weeks exhibited somewhat decreased 

feed intake and water intake, and weight loss compared 

to those fed pH 2.5 or pH 7.0 water; however, stomach 

pH values were not statistically different amongst treatment groups.403 Rats consuming water acidified to pH 

2.5 with HCl for six to 11 months showed no changes in 

weight and “negligible” damage to tooth enamel.397 Rats 

drinking water with pH 2 for 21 weeks drank slightly 

less than controls, while those consuming pH 3 water 

showed no measurable effects in any health parameter.404 

Water with a pH of 2.5 given to rats for 30 days resulted 

in decreased water intake, while water with pH 3 given to 

rats produced no growth deficits.396 Rats drinking water 

with a pH of 1.4-3.5 for 42-84 days showed accelerated 

erosion on the tooth surface; however, oral cavity pH was 

unchanged.405 Mice consuming acidified water (pH 2.0) 

for 120 days had slightly decreased reticuloendothelial 

clearance rates when compared to controls, possibly as 

a result of decreased growth and smaller spleens.406 It 

is questionable if the physiologic effects in these reports 

are a direct result of acidic water on systemic acid-base 

status, per se. Even a study that reported some relatively 

subtle effects (decreased gains) in rats at pH 2.5 or less, 

gastric pH was unchanged,403 and rats and rabbits fed pH 

2.3-2.5 water for seven months maintained normal blood 

pH.401

Several experiments reported no effects when acidic water 

was fed, and it is commonly believed that acidifying 

water to approximately pH 3 is beneficial in rodent colonies. Rats consuming water with pH of 2.5 gave birth to 

and weaned more pups than control animals.407 Rats and 

rabbits ingesting water at pH 2.3-2.5 for seven months 

showed no affect on health as measured by growth and 

multiple blood parameters.401

Summary

Existing human drinking water standards (pH 6.5-8.5) 

were established decades ago for aesthetic reasons (especially taste) and to protect plumbing from corrosion, 

rather than upon health-based criteria.392,408 Although 

a number of Cooperative Extension Service Web sites 

suggest water below this range will produce pathologic 

acidosis in cattle, none we examined offered hard evidence. Nor were we able to find any references to direct 

health effects of moderately acidic or basic water in animals. There are a number of references to the beneficial 

effects of acidifying laboratory animal and swine water 

with mineral acids to pH 3. The only adverse effects in 

these reports were relatively subtle and occurred at pH < 

3.0. The only example of feeding a pure mineral acid to 

ruminants (equivalent to approximately pH 2-3) resulted 

in acidified urine, but there were no adverse health effects 

over a several week period. There is no equivalent data 
33

for basic drinking water. From a purely pathophysiological standpoint, it seems unlikely that water with a 

pH between 3.0 and 7.0 would cause health problems 

in otherwise normally managed animals. An exception 

might be feedlot ruminants, which are often marginally 

acidotic as a metabolic consequence of the high soluble 

carbohydrate rations they receive. In this case, acid water 

might be sufficient to trigger a crisis.

The other potential adverse effects of basic or acidic water 

involve mobilization of potentially toxic substances (e.g. 

metals) from plumbing or soils. While it seems unlikely 

the amounts mobilized would be sufficient to actually 

cause poisoning under most conditions, it is quite probable they would be large enough to cause water refusal. 

Because the effect of any given pH on palatability 

depends upon what the water contacts, there is no way to 

make any wide-reaching recommendation in this regard.

We suspect the commonly touted acceptable ranges 

for drinking water pH (a low of 5.5-6.5 and a high 

of 7.5-9.0) are excessively conservative from a strictly 

animal health standpoint, at least on the acid side, but 

there are not sufficient experimental and/or clinical 

data to offer a specific alternative.
34
35

Selenium (Se), a metalloid that shares many chemical 

properties with S, is predominantly present in cretaceous 

rocks, volcanic material, seafloor deposits, and glacial 

drift in the Great Plains.409 It can be present in soil at 

levels sufficient to cause toxicity or low enough to result 

in deficiency in grazing animals. Either outcome can 

result in serious economic losses to livestock producers 

and illness and/or death in wildlife. Normal soil concentrations range from 0.1 to 2.0 μg total Se per gram of 

soil; however, in seleniferous areas such as Wyoming, soils 

can contain as much as 30-324 μg Se per gram of soil.410

Plants grown on such soils tend to accumulate Se and, 

depending upon the species, may, in fact, bioconcentrate 

Se to concentrations in excess of 10,000 ppm. 

Water in contact with seleniferous rocks and soils (e.g. 

irrigation wastewater) may also accumulate Se.411,412 The 

most common form of Se in Wyoming surface waters 

is the selenate (SeO4

2-) ion. “Normal” surface water is 

described as containing less than 2 μg Se/L411, and it is 

thus not normally a major source of Se for livestock and 

mammalian wildlife; however, poisoning as a result of 

seleniferous water has occurred in horses and sheep.413-415 

Dissolved Se becomes concentrated in successive levels of 

the aquatic food chain and is a major concern for waterfowl that depend upon aquatic biota for food411,416,417; 

however, aquatic bioconcentration does not pose a hazard 

to large herbivores (e.g. cattle, elk) under normal conditions as their intake of algae and aquatic organisms is 

very small. Interestingly, bioaccumulation of Se in the 

aquatic food chain actually removes Se from the water 

column,411,418 thus decreasing the risk to large mammals. Forages irrigated with seleniferous water contain 

elevated Se concentrations and can pose a risk to grazing 

animals.411,412,418 While each of the preceding sources is 

important, this report is concerned specifically with the 

hazard posed to livestock and wildlife by Se in drinking 

water and will focus upon that source.

Essentiality

Selenium is an essential trace element. Most authorities agree that, worldwide, deficiency is a more common 

problem than toxicity, and, thus, for the last 40 years, 

8 Selenium

much more research has focused upon the effects of 

inadequate dietary Se than too much. This research may 

still be useful for its insight to Se metabolism. Within the 

body, Se is a component of several enzyme systems, most 

involved in catalyzing oxidation-reduction reactions.419,420 

The Se-requiring system thought to be most responsible 

for damage in deficiency situations is glutathione peroxidase.410,421 Selenium supplementation decreases the incidence of white muscle disease, a degenerative condition 

in muscle resulting from oxidant stress.421-423 The FDA 

permits 0.3 ppm Se (total ration) as a feed additive, up to 

0.7 and 3 mg Se per head per day as a feed supplement 

for sheep and beef cattle, respectively, and in fortification 

mixtures up to 90 and 120 ppm Se for sheep and cattle, 

respectively.424 Deficiency is rarely a problem in Wyoming and northern Great Plains states.425,426 

Metabolism

Selenomethionine is the main form of Se in common 

forages, even though it is not a major component of accumulator plant species.427-429 It constitutes the majority of ingested Se, however, as accumulator plants are 

highly unpalatable and are usually avoided to the point 

of starvation.430 Waterborne Se, usually selenite (SeO3

2-) 

or selenate (SeO4

2-) ions, normally comprises a relatively 

small portion of large herbivores’ total exposure; however: 

1) water concentrations sufficient to cause poisoning 

have been recorded in Wyoming431,432; 2) poisoning has 

occurred in livestock as a result of Se contamination associated with mineral extraction; and 3) Se-contaminated 

water has the potential to add to the already high background forage concentrations common to many parts of 

the Great Plains.

Dietary Se is absorbed from the small intestine in both 

ruminant and monogastric species. Selenocysteine and 

selenomethionine are transported across the intestinal 

epithelium by active amino acid transport mechanisms.433 

Selenite is absorbed passively by simple diffusion, but 

SeO4

2- is accumulated via a Na-mediated carrier with 

sulfate (SO4

2-).419,434,435 To date, there is no evidence for 

homeostatic control of Se absorption as neither dietary Se 

concentration nor bodily Se status influences absorption 
36

efficiency.436,437 Absorption of Se is influenced by animal 

species and the form of Se ingested. Selenomethionine, 

the predominant form of Se in forage plants, is absorbed 

more efficiently than inorganic forms of Se, at least when 

the comparison is based upon tissue concentrations.438

Selenate is better absorbed than SeO3

2-, at least in laboratory rodents, and both are more efficiently absorbed 

than elemental Se.419 Ruminants reduce Se to unabsorbable selenides in the rumen and are therefore, to some 

degree, protected against poisoning. It is not unusual to 

see selenosis in pastured horses, while cattle on the same 

pasture remain unaffected.426 Because the reduction of 

Se by rumen microflora is heavily influenced by other 

dietary factors, ruminants also exhibit greater variation in 

Se absorption than monogastrics.415,439

Following absorption, Se becomes associated with plasma 

proteins, mainly albumin and selenoprotein-P, for transport to tissues.440 Selenomethionine is non-specifically 

substituted for methionine in protein437 and only becomes available for either toxicity or nutrition as the protein turns over. Other forms are incorporated into essential selenoproteins and/or methylated to dimethylselenide 

and the trimethylselonium ion for elimination.441 Both 

elimination and protein incorporation appear to involve 

metabolic activation to a reactive intermediate, which, 

when cellular defenses become saturated, is responsible 

for most of the toxic effects of Se.419 Under normal 

conditions trimethylselonium is eliminated via urine 

and, to a lesser extent, bile, but as tissue concentrations 

increase to toxic levels an increasing percentage is eliminated via respiration as dimethylselenide.419 Increased 

(i.e. potentially toxic) dietary Se also results in a shift of 

the distribution of Se between various proteins and body 

compartments411,438,442 although both the physiologic and 

toxicologic significance of this observation is yet to be 

elucidated.

Selenium interacts with a number of other common 

dietary constituents, primarily at the pharmacokinetic 

(uptake, distribution, and elimination) level. These 

interactions modulate both the nutritional and toxic 

properties of Se. Arsenic (As) decreases Se toxicity by 

decreasing tissue Se concentrations.35,38,443 Mercury decreases the toxicity of Se in birds37,435 and possibly marine 

mammals.411 Sulfur is thought to alleviate Se toxicity.444 

When sheep were given 2 mg of Se as sodium selenate 

(Na2SeO4), sheep receiving 0.05% dietary S showed a 

greater degree of Se toxicity when compared to sheep 

given 0.11, 0.17, or 0.24% S, mostly as added SO4.

445 

Dietary SO4 decreased the Se balance in dairy cows fed 

Na2SeO4, reduced the true availability of nutritional 

levels of Se, and increased its excretion via feces in dairy 

cattle.446 This interaction is hypothesized to occur as a 

result of S decreasing ruminal pH, altering Se metabolism 

to unavailable forms, as well as reducing the incorporation of dietary Se into ruminal bacteria.445,447 Ruminal 

interactions, however, are not the only explanation for the 

inhibitory effect of S on Se toxicity. Added dietary SO4

(0.29%) resulted in a 20% growth increase in rats fed 

10 ppm Se; 0.58% SO4 caused a 40% growth increase; 

and 0.87% SO4 slightly prevented liver damage due to 

Se intoxication.448 The interaction between SO4 and Se 

is not universal, however. Three thousand mg SO4

2-/L 

in drinking water failed to alter the uptake of sub-lethal 

dietary concentrations of sodium selenite (Na2SeO3) or 

selenomethionine in mallard ducks,449,450 and more research is needed to elucidate the conditions under which 

the protective interaction occurs. Cyanogenic glycosides 

block uptake of Se and ameliorate Se toxicity242,451 and 

have been investigated as a means of protecting livestock 

against selenosis. Copper and Cd have also been shown 

to reduce Se toxicity, though the mechanisms are not 

known.37,452 Increased dietary protein has been suggested 

to reduce the severity of poisoning.453 The type of feedstuff (alfalfa vs. grass hay) may influence the bioavailability of Se.242 Even being Se deficient predisposes animals 

to Se toxicity.454

Toxicity

Although essential, Se exhibits a very narrow margin 

of safety. Toxic effects have occurred in livestock at 

dietary concentrations only 40-100 times larger than 

deficiency.421 The form of Se administered influences 

tissue accumulation and thus toxicity.455-460 The chemical species most common in water are the inorganic ions 

SeO3

2- and SeO42-. Selenium toxicity can be manifested 

in two forms, acute or chronic. Acute toxicity usually 

results in GI, liver, kidney, and heart damage, shock, and 

sudden death.430,459,461 Selenium has also been implicated 

as a cause of hypertension and cardiac damage.462 Reproductive deficits, including teratogenesis and embryonic 

mortality, occur in avian species411,417,456,463; however, there 

is no evidence Se is teratogenic in mammals.464-466 Selenium may compromise reproduction in mammals.467,468 

Chronic selenosis (“alkali disease”) in ungulates is manifested most obviously as epithelial damage (hair loss and 

cracked hooves) as a result of necrosis of the keratinocytes450,469 and ill-thrift.
37

A single subcutaneous dose of 2 mg Se/kg BW given to 

pigs caused death after four hours.470 Three hundred 

seventy six of 557 calves injected with a Na2SeO4 solution that contained 100 mg Se (0.5 mg/kg BW), rather 

than the 12 mg Se that was intended, died within five 

weeks.471 Intramuscularly injecting 2 mg Se/kg BW as 

Na2SeO3 into four calves caused shock within three hours 

and death in 12 hours.472 Ewes injected intramuscularly 

with doses from 0.4-1.0 mg Se/kg BW exhibited dyspnea, anorexia, colic, and a seromucoid nasal discharge. 

Doses less than 0.6 mg/kg BW were not lethal within 

192 hours. The calculated LD50 was determined to be 

0.7+/-0.035 mg/kg.473 Injecting sheep intramuscularly 

with 0.68 mg Se/kg BW as Na2SeO3 produced death 

within 20 hours. Smaller doses took longer to be lethal, 

or they only caused reduced feed consumption and transient signs of intoxication.473 Ninety μg Se/kg BW, given 

intramuscularly as Na2SeO4, produced no clinical signs 

in ewes. Three hundred fifty μg Se/kg BW was lethal in 

some ewes. Barium selenate (BaSeO4), given similarly at 

rates of 0.225, 0.454, 0.908, 1.816, or 4.9 mg/kg BW 

produced no signs other than irritation at the injection 

site.474

Selenium fed as Na2SeO3 at rates of 22.3, 33.5, or 52.1 

ppm dietary Se to rats for 359 days resulted in the deaths 

of five of nine, eight of nine, and all nine rats in the three 

treatment groups, respectively, as well as decreased fertility and anemia in the population as a whole.475 An experiment focused on Se as a causative factor of tooth decay 

offered drinking water containing 3 mg Se/L as Na2SeO3

to rats for four weeks. Two of 15 rats died, and the others 

suffered significantly reduced feed consumption, water 

intake, and body weights.476 Rations containing 6.4 

ppm Se, as seleniferous wheat or Na2SeO3, resulted in 

significantly decreased growth and enlarged spleens in 

rats. Lower concentrations were without measurable effects. Higher concentrations resulted in decreased organ 

weights and anemia and were lethal in some rats.477

In one of the earliest controlled studies of Se doseresponse, Miller and Williams478 reported the single oral

“minimum fatal doses” (which they defined as a dose 

large enough to kill 75% of the test group) were 0.68 mg 

Se/kg BW for horses and mules, 1.1-2.2 mg Se/kg BW 

for cattle and 2.2-3.6 mg Se/kg BW for swine, all given 

as Na2SeO3. Although the experimental protocol was not 

up to modern standards, more recent reports in cattle and 

horses usually agree within two- to five-fold. Depression, 

anorexia, hind limb ataxia, and sternal recumbency developed in 256 pigs in a commercial piggery after the pigs 

were exposed to feed containing 84 ppm Se.479 Feed containing 8.1 ppm Se resulted in decreased feed consumption and paralysis in 54 feeder pigs.480 Rations containing 14.75 ppm and 26.65 ppm selenium caused hair loss, 

reddening of skin, and hind limb ataxia in 80 of 160 

pigs. Higher concentrations resulted in feed aversion.481

Porcine diets fortified with approximately 25 ppm Se as 

Na2SeO3 resulted in hair and hoof lesions and weight 

loss. Higher concentrations produced feed aversion and 

poliomyelomalacia.482 Corn, naturally contaminated 

with 10 ppm Se, fed for five months, resulted in two of 

five pigs developing alopecia and hoof lesions.483 Pelleted 

rations containing 26.6 or 31.7 ppm Se, fed as Na2SeO3 

or the Se-accumulator A. bisulcatus, respectively, and fed 

for several weeks, resulted in reduced feed consumption, 

alopecia, cracked hooves, and paralysis in pigs.457

A single dose of 5 mg Se/kg BW, given orally as Na2SeO3, 

was acutely toxic in lambs.484 Drenching 190 lambs with 

6.4 mg Se/kg BW resulted in the death of 180 within 15 

days.485 Twenty lambs, four to 14 days of age and averaging 4.5 kg, were mistakenly given 10 mg Na2

SeO3 (2.2 

mg Se/kg BW) orally to prevent white muscle disease; 

seven died within 17 hours, and eight more experienced 

diarrhea as a result of acute toxicosis. As a follow-up 

experiment, an additional ewe was injected with 0.45 mg 

Se/kg BW, which resulted in death within eight hours.486

Glenn et al.464 fed ewes increasing dosages of Na2SeO4

for 100 days and concluded the “minimum lethal” dose 

was 0.825 mg Se/kg BW/day. One of a group of 12 adult 

ewes and their lambs, pastured in an area of seleniferous 

forage and water, died following 14 days; other animals 

were unaffected when removed after four weeks. The 

exposure from the combination of contaminated forage 

and water was calculated to be 0.26 mg Se/kg BW/day.413

Sheep were lethally poisoned by grazing high Se forage 

(<49 ppm Se DM) and drinking high Se water (340-415 

μg Se/L) for four weeks; however, a similar group on a 

neighboring pasture with forages < 13 ppm Se and normal water were unaffected.413 

Steers gavaged with varying doses between 0.25 and 0.5 

mg Se/kg BW as Na2SeO3 exhibited inappetence, depression, and death. Two of eight died within eight weeks, 

and four more died within 14 weeks.487 Feeding 0.28 and 

0.8 mg Se/kg BW (approximately 10 ppm and 25 ppm 

Se, respectively, under range conditions) as selenomethionine or 0.8 mg Se/kg BW as Na2

SeO3 to yearling steers 

for four months resulted in overt clinical signs of alkali 

disease in one steer and histological lesions of dyskeratosis in several more.458 Primary antibody response was 
38

significantly impaired in the same dose groups.488 A dose 

of 0.15 mg/kg BW (approximately 5 ppm Se in diet), fed 

as either selenomethionine or Na2SeO3, and 0.28 mg/kg 

BW as Na2SeO3 in the same experiments were without 

measurable effects.458,488 Dosing calves with 0.25 mg Se/

kg BW as Na2SeO3 via bolus for 16 weeks resulted in hair 

and hoof lesions typical of selenosis and indications of 

increased oxidant stress.489 Decreased growth and anemia 

occurred in pre-ruminant calves fed 10 ppm as Na2SeO4

for 40 days, but no measurable effects occurred in calves 

fed 0.2-5.0 ppm Se.490

There is a relative paucity of quantitative data in horses, 

although horses are the species most commonly diagnosed with selenosis at the Wyoming State Veterinary 

Laboratory. Ponies dosed via stomach tube with 6 or 8 

mg Se/kg BW as Na2SeO3 developed signs of acute selenosis within six hours; ponies given 2 or 4 mg Se/kg BW 

remained clinically normal for the 14-day experiment.452

A 4-year-old gelding accidentally given 25 mg Se (0.055 

mg Se/kg BW) orally as Na2SeO4 for five consecutive days 

developed a straw-colored exudate on its lips, prepuce, 

and anus. Within three weeks, its hooves had separated 

from the coronary band, and alopecia was present on the 

mane and tail.491 This report did not investigate the Se 

content of the rest of the diet. Chronic Se toxicosis was 

diagnosed in seven horses consuming hay containing between 0.49 and 58 ppm Se (mean 22 ppm) in combination with a mineral supplement that contained 1.9 ppm 

Se.492,493 Eight of 20 horses developed alkali disease after 

being fed alfalfa hay that contained 5.9-17 ppm (mean 

= 11.9 ppm) Se for several weeks.494 Several horses were 

diagnosed with alkali disease in southeastern Idaho after 

being turned into a pasture where the only water supply 

contained approximately 0.5 mg Se/L.495 Assuming water 

consumption of 10% BW, this works out to 0.05 mg/

kg BW, but there was probably some additional Se from 

forage in the pasture. Feeding horses oats containing 

96 ppm added Se (19.2 ppm of total ration) as Na2SeO3 

for several months resulted in listlessness, loosening of 

hair, softening of the horny wall of hoof, and, ultimately, 

death.496 A 9-year-old gelding developed a swollen prepuce, vesicles on its nostrils and mouth, and hoof lesions 

of alkali disease after receiving 153.4 mg Se per day in his 

feed (16.4 ppm DM) for several days.497 In Queensland, 

Australia, horses and sheep were diagnosed with chronic 

and acute Se toxicity after grazing areas with vegetation 

containing 200-3,038 ppm Se and corresponding soil 

concentrations of 64-128 ppm Se.498 

In goats, daily oral doses of 5-160 mg Se/kg BW administered via capsules were uniformly lethal within 

31 days. Daily doses of 0.11-0.45 mg Se/kg BW were 

given for 225 days with no toxic effects.499 Elevated 

levels of selenium in the soil (1.45-2.25 ppm Se) and 

forage (40.32-80.64 ppm Se) in West Bengal, a state 

in India, have been blamed for a gangrenous condition 

(“Deg Nala”) in grazing buffaloes exhibiting hoof cracks, 

malaise, abdominal pain, laminitis, and edema on the 

tails and ear tips.500 Feeding captive pronghorn antelope 

grass hay that contained 15 ppm Se for 164 days did not 

result in any overt clinical signs but did decrease primary 

antibody response to a challenge with hen egg albumin.501

The foregoing notwithstanding, feeding steers seleniferous wheat, seleniferous hay, or a control diet with 

supplemental Na2SeO4 to supply 12 ppm dietary Se (65 

μg Se/kg BW/day) for 100 days did not produce any 

obvious evidence of selenosis.442,502 Ellis et al.503 fed adult 

Holstein cows up to 50 mg Se/head/day (approximately 

87 μg Se/kg BW/day) as Na2SeO3 for 90 days, followed 

by 100 mg Se/head/day (approximately 175 μg Se/kg 

BW/day) for another 28 days with no apparent health 

effects. Ewes tolerated 24 ppm dietary Se from Na2SeO3

or 29 ppm Se from A. bisulcatus for 88 days504 or 10-15 

ppm dietary Se through two pregnancies.505 Cristaldi et 

al.506 fed wether lambs Na2SeO3 at dietary Se concentrations up to 10 ppm for one year with no effect on rate 

of gain, serum enzymes, or pathology and concluded 

“≤10 ppm dietary Se as selenite is not toxic.” The same 

research group fed 4, 8, 12, 16, and 20 ppm dietary Se as 

Na2SeO3 to adult ewes for 72 weeks with no effect upon 

body weight nor other evidence of poisoning.507

Summary

Although the NRC421 suggests that horses are about as 

sensitive to oral Se as cattle, sheep, and goats, our research 

indicates that species sensitivity is horses > cattle > sheep 

and goats. Experience at several regional diagnostic labs 

indicates horses may be poisoned while ruminants using 

the same forage and water remain unaffected.426,508,509

With the exception of one study in antelope, there is 

insufficient dose-response data upon which to base safety 

recommendations in large mammalian wildlife. That 

said, there are reports of elk and deer sharing pastures 

with horses, sheep, and cattle, where the horses developed 

alkali disease, without any measurable ill-effects in the elk 

and deer.510 Thus, water that is safe for horses should be safe 

for other livestock and ruminant wildlife species. 
39

The effects of water-borne Se are, like many other elements, additive with feed content. The chemical form 

of Se in surface waters is predominately SeO3

2- or SeO42-, 

which is fortunate as these ions are the forms most 

thoroughly researched. In theory, relatively small concentrations of Se in water may be sufficient to push animals 

on moderately high Se forages over the edge of toxicity. 

Unfortunately, the Se content of forage and hay in this 

region varies from marginally deficient to downright 

toxic, and other dietary factors such as protein, vitamin 

E, or cyanogenic glycosides may modify the effects of a 

given concentration of dietary Se. For purposes of this 

report, we assumed a “typical” forage containing 1 ppm 

Se (mostly as selenomethionine), normal protein, vitamin 

E, and other trace element concentrations. The threshold for chronic poisoning in horses from the literature is 

0.05-0.1 mg/kg BW/day. This agrees with unpublished 

observations from our laboratories. Thus, water that 

contains 0.25 mg Se/L, consumed at a rate of 10% BW, 

combined with “average” Se forage, would constitute a 

potentially hazardous dose. In extremely hot weather, 

working horses drinking 20% BW of 0.125 mg Se/L 

water (a very conservative assumption) would receive a 

hazardous dose. 

In areas where forage Se concentrations are higher, or 

if horses are receiving dietary supplements that contain 

Se, safe water concentrations will have to be adjusted 

downward, but under normal conditions, 0.1 mg/L 

should not cause problems.
40
41

Sodium chloride (NaCl), or salt, was one of the first 

nutrients to be identified as essential to life. In ancient 

times, city locations were based upon the availability of 

salt, water, and food.511 Although ocean water contains 

approximately 2.68% NaCl and animals utilizing this 

environment face the challenge of coping with excessive 

salt, most terrestrial animals find it difficult to obtain 

adequate dietary salt and have developed methods to 

conserve NaCl.512-514 Due to the relative scarcity of salt 

in typical pastures, thousands of metric tons of NaCl are 

produced each year for use in mineral supplements.511 

Sodium (Na) and chlorine (Cl) are rarely found in elemental form in nature; however, most of the toxic effects 

of NaCl are due to Na. When appropriate, articles that 

mention one or the other separately will be cited.

Essentiality

Both Na and Cl are essential elements for practically all 

forms of life. Sodium (Na+) is the major extracellular 

cation while Cl- is the major extracellular anion; together, 

they are responsible for maintaining acid-base balance 

and regulating the osmotic pressure of bodily fluids.515,516 

Excitable cell membranes (e.g. nerve and muscle cells) 

depend upon tightly regulated Na+ and Cl- concentrations in cells and the extracellular fluid (ECF). Blood, a 

specialized form of ECF, consists of approximately 0.9% 

NaCl.514 Sodium chloride is reportedly the only mineral 

animals truly crave and will actually seek out.514,517 The 

dietary NaCl requirement of swine is between 0.10 and 

0.14%, and 0.18% Na is needed to achieve optimal 

performance.518-521 Similarly, the optimal dietary Na concentration in horses is 0.16-0.18% DM515 and for cattle 

is 0.08-0.1%.522 Under extreme conditions, such as high 

temperatures, lactation, or hard work, these requirements 

increase due to increased excretion of both Na+ and 

Cl-.

523,524 The clinical signs of sodium chloride deficiency 

are polydipsia (extreme thirst), polyuria (extreme urination), salt hunger, pica (licking foreign materials), weight 

loss, and decreased milk production.525,526 Chloride deficiencies have been produced by feeding diets with 0.10% 

Cl or less and present as anorexia, weight loss, lethargy, 

decreased milk production, polydipsia, polyuria, and 

cardiopulmonary depression, etc. as clinical signs.527-529

9 Sodium Chloride

Metabolism 

Once ingested, 85-95% of Na and Cl are absorbed in the 

GI tract, particularly the small intestine. Large amounts 

of Na and Cl are recycled into the intestinal tract via 

salivary, pancreatic, and intestinal epithelial secretions, 

as well as bile. The high intestinal Na+ concentration 

is required to transport glucose, amino acids, and other 

nutrients across the mucosa. Chloride is also secreted 

into the intestine to aid in creating the low pH environment needed for proteolysis. These secretions must then 

be reabsorbed further down the GI tract to conserve the 

elements.514 It has been suggested that elevated dietary 

NaCl can increase protein digestion. Hemsley530 discovered that increased NaCl in the diet increased the rate of 

passage of solid digesta from the rumen, which decreased 

microbial degradation within the rumen and increased 

the amount of protein available in the small intestine. 

Altered ruminal fatty acid concentrations have also been 

related to dietary NaCl.531-533 Dietary Na+ and Cl- in 

excess of physiologic requirements are usually efficiently 

eliminated from the body via the kidneys.534 

Potassium is the main intracellular cation, Na is the main 

extracellular cation, and Cl- is the main extracellular anion. The relative concentrations of these three elements 

creates an electrochemical gradient across cell membranes 

that is essential for nutrient transport, nerve conduction, 

muscle contraction, and energy generation, and they 

indirectly aid in maintaining pH balance. Imbalances 

of these elements result in a variety of disorders from 

decreased gains to acute death.535-537

Toxicity

The toxicity of NaCl is intimately related to the availability of water and is sometimes referred to as “sodium 

ion toxicity-water deprivation syndrome;” however, if the 

dose of Na+ is high enough, Na is toxic regardless of water 

intake.538 If adequate water is present, most animals can 

tolerate relatively large doses by increasing Na+ excretion.534,539-542 If sufficient water is not available, acute 

toxicosis results in dehydration, blindness, incoordination, convulsions, recumbency, and death.205,538,543,544 The 
42

normal physiological response to elevated dietary NaCl 

is increased water intake; however, if the water contains 

high NaCl concentrations, drinking results in even more 

NaCl intake and increases the risk of receiving a toxic 

dose.542 Even when sufficient potable water is available to 

eliminate excess dietary Na, every gram of NaCl excreted 

requires producing at least 5 ml of urine545 at a finite 

metabolic cost. Thus, slight to moderately elevated Na+

may impact growth and performance.542,546,547

The mechanisms underlying acute toxicity are related to 

cellular dehydration, or “tissue shrinking,” and edema. 

When extracellular Na+ concentrations become elevated, 

water is drawn out of the cell down the concentration 

gradient, resulting in shrinking.514,548 Eventually intracellular Na+

 concentrations adjust to a new equilibrium with 

the extracellular fluid (ECF), and cells return to their 

normal volume. By two to three days of exposure to elevated Na+

, neurons have replaced the increased intracellular Na+

 with “idiogenic osmoles,” hydrophilic, organic 

molecules that compensate for the attraction of extracellular Na+

 for water.549 Tissue shrinkage due to elevated 

ECF Na+ results in damage to the small blood vessels 

that supply the superficial portions of the brain. Later, 

after animals have adapted to elevated extracellular Na+

concentrations (whether from excessive dietary Na intake 

or water deprivation) and are allowed free access to water, 

the extracellular fluid becomes diluted and water is drawn 

back toward the elevated osmolarity inside the neurons, 

resulting in cellular swelling and damage. In either case, 

clinical signs result from cerebrocortical (brain) damage.

Acute toxicity has been observed in cattle, pigs, dogs, and 

rats after ingestion of extreme concentrations of NaCl. 

Ninety-one cattle developed muscular weakness, muscle 

fasciculations, and sternal and lateral recumbency, and 

they subsequently died, as a result of drinking water from 

a tank and lagoon that contained 4,370 and 21,160 mg 

Na+/L, respectively.205 Cattle consuming water containing 5,850 mg Na+

/L experienced a 13.7% reduction 

in body weight, with corresponding reductions in feed 

and water intakes.550 Water containing 6,726-6,826 mg 

Na+/L resulted in a loss of condition, scouring, and death 

in 15 of 220 cattle.551 Six cattle began showing signs of 

CNS disruption four hours after consuming 50 kg of a 

supplement containing 50,000 ppm NaCl (19,500 ppm 

Na), despite drinking water immediately afterward.538 A 

pig owner replaced free-choice NaCl as a salt block with 

two “handfuls” of loose trace mineral salt in 30 gallons of 

water. Within six days, four pigs began champing jaws, 

frothing at the mouth, and convulsing, and two ultimately died.552 Abruptly switching gilts to a diet containing 13,600 ppm NaCl resulted in feed refusal and watery 

diarrhea lasting several days.553 Dosing an 11.3-15.9 kg 

(25-35 lb) pig with approximately 178.6 g NaCl (69.6 

g Na+) in 500 ml water resulted in death within 15 

minutes.554 A female dog became blind, convulsed, and 

eventually died after consuming seawater (26,800 mg 

NaCl/L) on a hot summer day.544 Three female Boston 

terriers became ataxic, convulsed, and later died after 

drinking water contaminated with brine and containing 

approximately 100,000 mg NaCl/L.555 A male Airedale 

terrier began having seizures and eventually died after 

ingesting a bolus of a salt-mixture clay. The concentration of NaCl in the clay was not reported; however, it 

was stated a minimum of 20 g NaCl still remained in the 

dog’s stomach.548 The minimum toxic dose in canines 

was estimated at 2,000 mg NaCl/kg BW (780 mg Na/kg 

BW).556 Rats refused to drink water containing 25,000 

mg NaCl/L; death occurred after several days of water 

refusal were followed by gorging on water.557

Chronic toxicity has been investigated under both field 

and experimental conditions. Cattle consuming water containing 12,000 mg NaCl/L (4,680 mg Na+

/L) 

throughout the summer months did not become clinically dehydrated, but they did exhibit diarrhea, a 28.2% 

reduction in feed intake, and a 69% increase in water 

intake.558 Cattle ingesting water containing 2,500 mg 

NaCl/L (975 mg Na+/L) for 28 days showed increased 

water intake, decreased milk production, and diarrhea.547

Steers fed diets containing 50,000 ppm NaCl (19,500 

ppm Na) for up to 175 days gained less weight and 

utilized organic matter less efficiently than controls.531 

Steers fed high grain diets containing 70,000 ppm NaCl 

(27,300 ppm Na) for 126 days showed increased water intake, decreased feed intakes, and altered digestion 

patterns.559 Feeding lactating cows low fiber diets in 

conjunction with concentrate containing 60,000 ppm 

NaCl resulted in a 6.9% decrease in organic matter 

consumption and a 22% increase in water intake, but 

these diets had no effect on milk production.560 Lactating heifers supplemented with 136 g NaCl/day, beginning 42 days prepartum and continuing until 10 days 

postpartum, showed an increased incidence of udder 

edema.561 Water containing 15,000 mg NaCl/L resulted 

in decreased feed consumption, decreased body weight, 

and increased water intake in sheep.546 Drinking water containing 10,000-13,000 mg NaCl/L resulted in 

neonatal mortality and distress at parturition when given 

to twin-bearing pregnant ewes.562 Sheep drinking water 
43

containing 15,000 mg NaCl/L for 21 days consumed less 

feed and more water than controls.542 Sheep consuming water containing 20,000 mg NaCl/L for three days 

experienced a sharp decline in feed intake. After five 

days drinking the water, the animals’ feed consumption 

eventually recovered, suggesting an adaptive response.563 

Lambs given 2 g NaCl/kg BW from an early age had 

significantly lower growth rates, reduced feed intakes, and 

diarrhea in comparison to controls.564 Pigs consuming 

15,000 mg NaCl/L water for 30 days became stiff legged 

and nervous, and they had reduced water intakes.565

Hypertension has been produced in rats by offering water 

containing 10,000-25,000 mg NaCl/L for six months 

or longer.566-568 Feeding trials determined the chronic 

oral LD50 of NaCl fed to rats for 100 days was 2.69 g/kg 

BW.569

Toxicity has also been shown to occur when elevated 

dietary NaCl is coupled with water restriction. Feeding 60 3-year-old steers a supplement containing 4.5 kg 

NaCl one day prior to withholding feed and water (to 

obtain fasting body weights) resulted in blindness, incoordination, knuckling of fetlocks, and recumbency in five 

animals.543 Goats offered diets containing 30,000 ppm 

NaCl for 30 days showed a 20% decrease in feed intake 

when water was freely available and a 43% reduction 

when water was restricted.570 Pigs fed NaCl at the rate 

of 2.4 g/kg BW with restricted water showed “extreme 

signs” of NaCl toxicity and ultimately died.571 Sodium 

chloride poisoning was diagnosed in a herd of pigs that 

exhibited convulsions, an unsteady gait and muscletwitching, blindness, and rapid breathing. The pigs had 

been without water for an undetermined amount of time, 

and no levels of dietary NaCl were given.572 Swine began 

having convulsions and were exhibiting head pressing 

within three days of being purchased at an auction. It 

was determined the clinical signs developed as a result 

of the pigs receiving a high salt diet prior to the sale and 

then receiving no water during the auction.573

There are several reports that indicate at least some Na 

can be tolerated. Offering cattle water containing 4,110 

mg NaCl/L resulted in increased water intake and diuresis; however, no other effects on animal health were noticed.574 Cattle consuming water with 5,000 mg NaCl/L 

(2,000 mg Na+/L) appeared clinically normal throughout 

the course of two 30-day experiments.539 Steers consuming 192-193 g NaCl/day for 84 days showed no 

observable negative effects when ingesting a roughage 

diet; however, when fed a corn silage diet, the animals 

consuming the high Na diet had reduced weight gains 

and feed efficiencies. Roughage diets tend to increase 

water intake, potentially diluting NaCl and decreasing its 

effects.532 Sheep consuming water containing 13,000 mg 

NaCl/L for up to 16 months increased their water intake, 

but they exhibited no other adverse health effects.540,575-580 

Rations with a NaCl concentration of 91,000 ppm fed to 

sheep caused no significant effects on breeding, gestation, 

lambing, or wool production.581 Swine consuming 5,150 

mg NaCl/L water had a drastic increase in water intake; 

however, no other adverse effects were noticed.582

The limited data available regarding Cl- in water seems 

to indicate it is primarily a palatability factor. The EPA’s 

secondary water standard for human consumption 

suggests that more than 250 mg Cl-/L imparts a “salty” 

taste.583 Water containing 5,000 mg CaCl2/L offered to 

cattle resulted in water refusal despite lack of any other 

water sources. Water containing 3,000 mg/L resulted in 

increased water consumption and urinary acidification 

but no measurable effects on performance or health.584 

The SO4

2- ion was less palatable to beef heifers than 

the Cl- on an equimolar basis.585 Rats drinking water 

containing 10,000 mg CaCl2/L were unable to produce 

normal litters, and 15,000 mg CaCl2/L reduced growth 

rates.586 Conversely, in another study, rats consuming 

15,000 mg CaCl2/L adapted, grew normally, reproduced, 

and were able to suckle their young.557 

Summary

The effects of Na and Cl are difficult to separate since 

neither exists in its pure state in nature, and the elements 

usually occur together in water. It is also difficult to separate the chronic effects of NaCl from those attributed to 

TDS in the literature, as the Na+ and Cl- ions are major 

constituents of salinity under natural conditions. Nevertheless, it is the Na+

 ion that seems to be responsible for 

most of the recognized effects of “salt” poisoning.583 At 

present, there is not sufficient data to make any specific 

recommendations regarding Cl- in drinking water for 

livestock or wildlife.

The toxic effects of Na are very dependent upon the availability of fresh water. If abundant, good quality drinking 

water is available, animals can tolerate large doses of Na. 

This fact notwithstanding, at some point excess dietary 

Na exceeds the ability of the organism to excrete Na+, and 

acute poisoning results, regardless of water intake. The 

threshold for acute toxicity seems to be approximately 

1g Na/kg BW for swine, with cattle equal or slightly less 

sensitive and sheep considerably less sensitive (roughly 
44

2.5 g Na/kg BW). Most animals will limit their consumption of NaCl to approximately 400 mg Na/kg BW/

day, if possible. Beyond this dose, feed intake, water 

consumption, and productivity decline. We couldn’t find 

sufficient equine-specific data to nominate a toxic dose, 

but most reviewers indicate horses are roughly similar in 

sensitivity to cattle and swine. Similarly, there is virtually 

no quantitative data on wild ungulates, but there is no 

reason to suspect wild ruminants are significantly more 

sensitive than cattle.

If the only water available is also the major source of 

dietary Na, long-term impacts will occur at lower dosages. Chronic health effects, mainly decreased production, have been reported at water concentrations as low 

as 1,000 mg Na+/L in dairy cows; however, other studies 

with beef heifers in cooler climates reported only minimal 

effects at 1,600-2,000 mg Na+/L. Interestingly, the actual 

doses of Na consumed by the cattle in all of these studies 

(250-400 mg Na+/kg BW) were similar. Dosages greater 

than 800 mg Na/kg BW resulted in effects ranging from 

weight loss and diarrhea to death. 

It is theoretically possible animals maintained on highNa+ water for prolonged periods will, if suddenly exposed 

to low-Na+ water, develop acute Na+ ion intoxication, and 

anecdotal reports suggest that such has happened under 

field conditions. We were unable, however, to discover 

sufficient quantitative information to make any recommendations other than animals should be transitioned 

from high to low Na+ water sources gradually.

Assuming water consumption typical of a rapidly growing steer (see Introduction) and only background feed 

Na concentrations, the no-effect level would be about 

1,000 mg Na+/L or 2,500 mg NaCl/L. Serious effects, 

including death, become likely at 5,000 mg Na+/L. We 

recommend keeping drinking water Na concentrations 

at less than 1,000 mg/L, although short-term exposure 

to concentrations up to 4,000 mg/L should be welltolerated.
45

Sulfur (S) occurs in nature as free S or combined with 

other elements in sulfides and sulfates. The most common form in water is the sulfate (SO4

2-) ion, although 

some sulfurous wells may contain relatively high concentrations of dissolved sulfides. The latter do not persist 

for long under surface conditions but may contribute to 

health problems while they are present. Sulfides in igneous and sedimentary rock are oxidized to sulfate (SO4

) 

during the weathering process. The resulting sulfate salts 

are leached from soils by runoff and may be concentrated 

by evaporation in playas. Some aquifers are naturally 

very high in SO4

2-. Once SO42- is dissolved in water it 

cannot be removed unless it is reduced to sulfide by anaerobic organisms and precipitated in sediments, released 

as hydrogen sulfide (H2S) or incorporated into organic 

matter.587 Reverse osmosis, distillation, and ion exchange 

may be used to remove SO4

2- from water; however, none 

of these processes is cost-effective for livestock under 

normal conditions. Sulfur may also be present in organic 

compounds synthesized by aquatic biota; however, this 

form is usually a relatively minor component of the total 

water S content. In 1997, 11.5% of 454 forage/water 

pairs collected from around the United States yielded 

dietary S concentrations potentially hazardous for cattle. 

Thirty-seven % of these elevated pairs originated from the 

western United States, including Wyoming.588

Essentiality

Sulfur is essential for health and, in fact, comprises 

about 0.15% of the total body in mammals, where it is 

a constituent of the amino acids methionine, cysteine, 

cystine, homocysteine, cystathionine, taurine, and cysteic 

acid. It is also a component of biotin, thiamin, estrogens, 

ergothionine, fibrinogen, heparin, chondroitin, glutathione, coenzyme A, and lipoic acid.589 Calves deprived of 

dietary S had smaller livers, spleens, and testes, and larger 

brains and adrenals than controls.590 Lactating dairy cows 

require between 0.17% and 0.20% total dietary S to 

remain in positive balance, as S constitutes an estimated 

0.78% of milk proteins.591 The nutritional S requirement 

of monogastric mammals must be provided as two amino 

acids – methionine and cystine. Ruminants can use 

either preformed amino acids or synthesize S-amino acids 

10 Sulfur

from inorganic S; however, the efficiency of the latter 

process varies with other dietary conditions.592-594 

Metabolism

The first step in ruminal synthesis of S-amino acids from 

inorganic S is reduction of the latter to H2S.595 Not surprisingly, SO4

 is converted to H2S more efficiently than 

pre-formed S-amino acids. Halverson et al.596 examined 

sulfide production from various S sources and found 

methionine produced one third the amount of sulfide as 

SO4. Under normal circumstances, the reactive sulfide 

ion is combined with carbon by rumen microflora to 

create methionine, homocysteine, cystathionine, cysteine, 

and other S-amino acids. Under conditions of excessive S 

intake, however, significant quantities are reduced to H2S, 

and the very toxic gas escapes from the rumen into the 

systemic circulation resulting in poisoning.597-601

Excess rumen sulfide may also interact with certain 

trace elements, especially Cu, decreasing bioavailability 

and possibly resulting in serious nutritional deficiencies.241,447,602-604 In ruminants, S combines with Mo to 

form thiomolybdates. These, in turn, form unabsorbable 

complexes with Cu, which irreversibly bind to the solid 

phase of the digesta, resulting in Cu deficiency.241 It has 

also been suggested that thiomolybdates interfere postabsorptively with Cu incorporation into the enzymes 

superoxide dismutase and cytochrome oxidase, compromising mitochondrial integrity and cell function.230,241,605 

Finally, it has been theorized that some of the effects of 

excess dietary Mo are actually due to Mo toxicity per se 

and not to hypocupremia.241 Of the three elements, Cu, 

Mo, and S, S provides the most variation in nutritional 

outcomes due to its multiple metabolic pathways from 

the rumen. Sulfur exits the rumen principally as sulfide, 

but it can also leave as undegraded protein S or be incorporated into microbial protein. Inorganic S from diet, 

saliva, or degraded protein is the only form of S that will 

interact with Mo and Cu. Several factors affect protein 

degradation to S, including the supply of degradable 

nitrogen, the rate of ingestion, the specific population of 

rumen microbes, and the availability of readily fermentable carbohydrates.241
46

Dietary S may also antagonize Cu metabolism in the 

absence of excessive Mo. Copper deficiencies occurred 

in cattle fed 0.3% total dietary S606, and 500 mg S/L 

water was hypothesized to cause secondary deficiency as 

it raised dietary S to 0.35%, both in the absence of excess 

Mo.230 Sulfur inhibits the uptake of Zn. The interaction between Zn and S is further magnified if animals are 

fed a high fiber diet.603 Sulfur also decreases the uptake 

of dietary Se.445,607 High dietary concentrations of S are 

thought to reduce rumen pH, favoring the conversion 

of Se to biologically unavailable selenide.445,608 Sulfur 

may also reduce incorporation of dietary Se into ruminal 

bacterial protein.447 Interestingly, S has been shown to 

protect against Se intoxication under some circumstances.445,448

Monogastric animals lack the ability to produce S-amino 

acids from inorganic S and are thus somewhat less sensitive to the above-mentioned toxic effects of the sulfide 

ion. For example, the NRC “maximum tolerable” S 

concentration for range cattle is 0.5%, whereas 0.69% of 

diet is optimal in rats.589 Although it is possible for a monogastric to generate toxic concentrations of H2

S following ingestion of elemental S, the dosage required is much 

greater than in ruminants. To illustrate this, 14 horses 

were mistakenly fed between 0.2-0.4 kg of flowers of S 

(99% S) resulting in a dose between 333-666 mg/kg BW 

(corresponds to 11-22% dietary dry matter). The horses 

became ill within 12 hours, and two died after 48 hours. 

Post mortem examination of the two deceased animals 

revealed cranioventral consolidation of the lungs, hemorrhaging throughout the heart and GI, and congestion of 

the liver.609 Toxic effect(s) of inorganic S salts (e.g. SO4) 

in monogastric species are usually related to abnormalities 

in water balance in the GI tract, explaining why clinical 

signs differ between monogastric and ruminant mammals. In swine, toxic effects are generally manifested as 

watery feces and have been shown to occur when ingesting water with concentrations as low as 600 mg SO4

2-/L, 

but they more commonly occur in water containing 

1,600 mg SO4/L or higher.610-612 

Toxicity

As with all poisons, toxicity depends on dose, route of 

exposure, and form of the element. In this report, we are 

most interested in ingestion (oral exposure) and SO4

2-, 

as that is the form of S commonly found dissolved in 

water. Between 0.3-0.5% of dietary dry matter is the 

recommended maximum tolerable limit for total daily 

S intake for ruminant animals.589 The amount of S that 

water contributes to the diet depends on the amount of 

water an animal drinks as well as the concentration of S 

in the water. This varies drastically with environmental 

temperature, type of feed, and condition of the animal. 

In one published example, the amount of S contributed 

by 1,000 mg SO4

2-/L in drinking water varied from 

0.1-0.27% under different conditions.613 

Toxic S concentrations have been shown to reduce the 

feed intake, water intake, growth, and performance of 

animals. Cattle given water containing 1,219 mg SO4

2-/L 

in conjunction with a diet containing 0.16% S (0.29% 

total S intake), exhibited depressed dry matter intake 

(DMI).614 Adding 0.72% SO4 (0.24% dietary S) to cattle 

diets reduced weight gains by 50% after the first two 

weeks.615 Concentrations of 0.35% or more dietary S resulted in diminished DMI in lactating dairy cows.591 Water containing 5,000 mg sodium sulfate (Na2

SO4)/L and 

grass hay containing “0.75% SO4” reduced water intake 

by 35% and feed intake by 30% in cattle.574 Decreases in 

average daily gain (ADG), feed efficiency, and dietary net 

energy were seen when heifers were fed 0.25% S as ammonium sulfate ((NH4

)

2

SO4).616 Supplying heifers with 

water containing 2,814 mg SO4/L and hay containing 

“0.55% SO4” reduced hay intake by 12.4% during the 

summer months.617 Water containing 3,087 mg SO4/L 

reduced ADG by 27%, DMI by 6.2%, and water intake 

by 6.1 L in steers, and it increased the incidence of polioencephalomalacia (PEM).618 Cattle on a low plane of 

nutrition decreased their water intake when consuming 

water with 1,000 mg SO4/L, and cattle on a high plane of 

nutrition had a slight decrease in feed intake when consuming 2,000 mg SO4

/L.619 Concentrations of S greater 

than 0.4%, added as elemental S or Na2SO4, decreased 

gains in feeder lambs.594 Approximately 0.5% S added 

to rations as calcium sulfate (CaSO4) or Na2SO4 resulted 

in reduced feed intake and daily gains of 163 g/day and 

191 g/day, respectively, compared to control lambs that 

gained 251 g/day.620

On the other hand, when 0.75% S was added as CaSO4

to the concentrate portion of the diet (0.477% total 

dietary S) of six Hereford cattle, no statistically significant 

changes in serum enzyme activity, Se concentrations, 

weight gains, or general health were noticed.621 The study, 

however, was designed to look at S-Se interactions and 

lacked statistical power to examine growth, ADG, or 

other measures of performance, and one of the animals 

died of PEM at the end of the experiment. Cattle offered 

water containing 2,500 mg SO4/L showed no changes 
47

in feed or water consumption. The animals consumed 

an average of 3.9 kg of hay, 3.1 kg concentrate, and 33.1 

kg water per day, suggesting this level as a safe tolerable 

limit.585 As with the previous study, the number of animals tested was very small. Sublimed S added to the diet 

of steers for 10 weeks at 0.42% did not affect feed intake 

but did at 0.98%.622 Qi et al.623 added various amounts 

of CaSO4 to the diet of goats and concluded that optimum feed performance occurred between 0.2-0.28% 

S.623 Pendlum et al.624 fed up to 0.3% elemental S to 

steers without adverse effects. 

The most dramatic manifestations of S toxicity in ruminants are sudden death, with no lesions, and/or PEM. 

Polioencephalomalacia is a neurological disease of cattle 

and sheep, resulting in seizures, ataxia, blindness, and 

recumbency as the main clinical signs. It is usually fatal. 

Seven hundred of 2,200 ewes grazing a pasture previously sprayed with elemental S began showing signs of 

abdominal discomfort within two hours of exposure, and 

220 ewes died within five days. Lesions of PEM were 

found only in the sheep that had survived for five days.625

Animals ingesting water with 4,564 mg SO4/L and feed 

containing 0.17% S had a 47.6% incidence of PEM 

and a 33% mortality rate.626 Six of 110 cows drinking 

7,200 mg Na2SO4/L water developed PEM.627 Eighteen 

of 21 herds fed supplements containing 2% inorganic 

SO4 developed PEM. This supplement provided approximately 0.16% S beyond what was in the rest of the 

diet.628 Water containing 2,000 mg SO4

2-/L produced 

PEM in one of nine steers.597 Three of 21 steers fed 3,780 

mg SO4

2-/L developed PEM and died. Feeding thiamin 

did not prevent S-toxicity.629 Four steers died of PEM 

on a feedlot in Alberta, Canada, after consuming water 

with 5,203 mg SO4/L while the temperature was 30 C.630 

Four of 40 animals developed PEM after ingesting hay 

with 0.39% S and water containing 2,250 mg SO4/L.631 

All 10 experimental animals offered water with 5,540 

mg S/L or 7,010 mg S/L showed signs of PEM.632 The 

incidence of death from PEM in a beef feedlot varied 

dramatically with environmental temperature, from none 

in the winter to 0.8% per month in the summer. The 

increase also corresponded with a 2.4-fold increase in 

water intake as a result of summer weather, raising total 

dietary S intake to 0.67%.633 Cows in Canada were 

stricken with PEM when exposed to 3,400 mg SO4

2-/L 

water; no new cases occurred after the water was replaced.634 Sixty-nine animals were affected with PEM 

after ingesting a protein supplement containing “1.5% 

organosulfate” and water containing 1,814 mg SO4/L.205 

Experimentally feeding 0.477% total dietary S resulted in 

one of 12 heifers developing PEM three days after termination of the experiment.621 Polioencephalomalacia has 

been diagnosed in wild ruminants.635,636 Tests were not 

conducted to confirm SO4 as the cause of these cases, but 

surface waters in the area where the animals were found 

are naturally high in SO4, and exposure to these waters 

was considered likely.637

Sulfate waters are quite unpalatable, and, when given a 

choice, animals will discriminate against them. A taste 

test was conducted between waters containing 1,450 

mg/L and 2,150 mg/L SO4 and tap water. The cattle 

discriminated against the water containing 1,450 mg/L 

and rejected the water containing 2,150 mg/L, opting 

for tap water instead.617 Despite the unpalatability, if no 

other water is available, animals will reluctantly drink water with higher SO4

 concentrations resulting in potential 

toxicity.

Summary

In ruminants, high dietary S may cause acute death, 

PEM, trace mineral (especially Cu) deficiencies, and/

or chronic, as-yet-poorly-defined ailments that decrease 

production efficiency. All dietary sources of S (water, forage, concentrates, feed supplements) contribute to total S 

intake and thus to potential toxicity. The S contribution 

of water, usually as the SO4

2- ion, varies dramatically with 

environmental conditions as water consumption goes up 

and down.

From a strictly theoretical standpoint, the NRC maximum tolerable dose of S for cattle is 0.5% of the total 

diet (0.3% for feedlot animals).589 Wyoming grasses are 

reported to contain between 0.13%-0.48% S.638 Assuming forage S concentrations of 0.2% and water consumption typical of young, rapidly growing cattle at summer 

temperatures (30 C), a water SO4 concentration of 1,125 

mg/L will meet or exceed the NRC’s maximum tolerance limit for S in cattle. Adult bulls, which consume 

half as much water, could theoretically be impacted by 

2,250 mg/L, and lactating cows would fall somewhere in 

between. In practice, water SO4 concentrations as low 

as 2,000 mg/L have caused PEM and/or sudden death in 

cattle. This observation is supported by many field cases 

investigated by the WSVL and other regional diagnostic 

labs since 1988. It seems to be contradicted by some of 

the early studies mentioned above, notably Digesti and 

Weeth585, but both probability and the morbidity of poisoning increase with progressively larger SO4

 concentra-
48

tions; thus, studies with small numbers of animals easily 

overlook marginally toxic doses. Anecdotal data also indicate cattle are able to adapt to elevated S concentrations 

if introduced gradually to potentially toxic waters over a 

period of several days to weeks. The details (i.e. how rapidly dietary S can change) of this process and the effect(s) 

of other dietary factors such as energy and protein on the 

process are still a matter of conjecture.

Waterborne SO4 is reported to decrease Cu uptake at 

concentrations as low as 500 mg S/L as SO4

2-.602,606 

Whether overt Cu deficiency results depends upon the 

dietary concentration of Cu, and excess dietary Cu may 

compensate for some or all of the effect of SO4

2-.308 

Unfortunately, most Wyoming forages are marginally to 

drastically deficient in Cu for cattle. Elevated dietary S 

also interferes with the uptake of Zn and Se. Trace element deficiencies are multifactorial diseases that do not 

normally manifest themselves unless animals are exposed 

to other stressors such as bacterial pathogens, bad weather, shipping, etc. Therefore, it is difficult, if not impossible, to settle upon a single number that consistently 

results in deficiency or guarantees safety; however, the 

NRC recommends “the sulfur content of cattle diets be 

limited to the requirement of the animal, which is 0.2% 

dietary sulfur for dairy and 0.15% in beef cattle and 

other ruminants.”589

Relatively low S concentrations (equivalent to 500-1,500 

mg SO4

2-/L in water) have also impacted performance 

(e.g. ADG, feed efficiency) in feedlot and range cattle 

via a variety of mechanisms not completely understood.614,616,639,640 Loneragan et al.597 suggested that 

H2S produced from SO4

2-, eructated and then inhaled, 

resulted in pulmonary damage and increased susceptibility to respiratory infections. Elevated SO4

2- also results 

in decreased water intake under experimental conditions. 

Finally, it is possible some, as yet unrecognized, interactions with other dietary components result in decreased 

utilization and feed efficiency. These effects have obvious 

implications for animal health, but they are difficult to 

quantify under field conditions. 

Monogastrics, such as horses, are at less risk of S effects 

that involve ruminal generation of sulfide. In these species, the principle effect of elevated drinking water SO4

seems to be diarrhea resulting from the osmotic attraction of water into the gut. The relative contributions of 

the SO4

2- ion and its associated cation are unclear, but 

the literature indicates the effect 1) is transient and not 

life-threatening and 2) probably only occurs at concentrations considerably in excess of those toxic in ruminants. 

Therefore, concentrations that are safe in ruminants 

should provide adequate protection for horses.

Assuming normal feedstuff S concentrations, keeping 

water SO4

2- concentrations less than 1,800 mg/L should 

minimize the possibility of acute death in cattle. Concentrations less than 1,000 mg/L should not result in 

any easily measured loss in performance.
49

Total dissolved solids (TDS) is defined as all inorganic 

and organic substances contained in water that can 

pass through a 2 micron filter. In general, TDS is the 

sum of the cations and anions in water. Ions and ionic 

compounds making up TDS usually include carbonate, bicarbonate, chloride, fluoride, sulfate, phosphate, 

nitrate, calcium, magnesium, sodium, and potassium, but 

any ion that is present will contribute to the total. The 

organic ions include pollutants, herbicides, and hydrocarbons. In addition, soil organic matter compounds such as 

humic/fulvic acids are also included in TDS. There are a 

variety of ways to measure TDS. The simplest is to filter 

the water sample, and then evaporate it at 180° C in a 

pre-weighed dish until the weight of the dish no longer 

changes. The increase in weight of the dish represents the 

TDS, and it is reported in mg/L. The TDS of a water 

sample can also be estimated fairly accurately from the 

electrical conductivity of the sample via a linear correlation equation dependent upon specific conductivity. 

Finally, TDS can be calculated by measuring individual 

ions and simply adding them together. 

Total dissolved solids is a non-specific, quantitative measure of the amount of dissolved inorganic chemicals but 

does not tell us anything about its nature. TDS is not 

considered a primary pollutant with any associated health 

effects in human drinking water standards, but it is rather 

used as an indication of aesthetic characteristics of drinking water and as a broad indicator of an array of chemical 

contaminants.

Essentiality

Although many essential elements may contribute to 

TDS, the measurement technique does not, itself, differentiate essential from toxic elements. 

Metabolism

Since TDS represents an undifferentiated collection of 

just about everything dissolved in a water sample, it is 

impossible to speak of the “metabolism” of TDS.

11 Total Dissolved Solids (TDS)

Toxicity

Interestingly, early epidemiologic studies suggested that 

“moderately high” TDS concentrations (“high” in this 

context being less than 1,000 mg/L) protected people 

against cancer and heart disease.641-644 Although the 

mechanism(s) underlying these early observations are not 

completely understood, it was first narrowed down to 

“hardness” as opposed to TDS. It now appears certain 

constituents of TDS, notably Mg, interfere with the 

formation of thrombi in arteriosclerosis.641,645 Another hypothesis for the protective effect is that some components 

of hardness decrease leaching of toxic elements from 

plumbing.644 The inclusion of other cardiac risk factors, 

such as Na, in the total TDS of earlier studies probably 

accounts for the conflicting results in the older literature.

Saline waters may adversely impact animal health by 

several possible mechanisms. One of the most important biological functions of water in mammals is as a 

solvent for nutrients, waste products, etc. The presence 

of extraneous solutes decreases the ability of water to 

serve this function by decreasing its ability to dissolve 

additional solutes. A similar, related factor is plasma 

osmolarity. Solutes exert an attraction on water across 

membranes, and inappropriate water movement is disastrous to cells and tissues. An extreme example of this 

effect is water intoxication that results in death, as was 

the case with a young woman in California.646 Mammals 

expend a considerable amount of energy maintaining 

the osmolar concentration of various body compartments within a fairly narrow range. The presence of 

excessive solutes in drinking water adds to this burden 

and consumes resources that would otherwise be used 

for growth, milk production, or fighting off disease. It is 

well-accepted that extreme drinking water TDS concentrations in the 1.5%-3% range are incompatible with 

life546,551,557,586,647,648; however, the effects of lower TDS 

concentrations are too multifactorial, involving species, 

age, sex, diet, pregnancy, lactation, environmental conditions, etc., to lend themselves to simple all-or-nothing 

results. Also, the fact animals may “tolerate” (in other 

words, survive) a particular concentration is not the same 

as proving they remained productive on it.
50

Elevated TDS adversely affects the palatability of water. In humans, taste panels rated the palatability of 

water with 300 mg/L as “excellent,” 300-600 mg/L 

“good,” 600-900 mg/L “fair,” 900-1,200 mg/L “poor,” 

and greater than 1,200 mg/L “unusable.” Earlier criteria for human health were based upon this fact.649 In 

livestock, decreased palatability is well-recognized as 

an important determinant of water consumption and, 

indirectly, feed consumption and performance. Cattle 

given water containing 6,000-15,000 mg/L TDS exhibited decreased water intake, feed intake, and average daily 

gain (ADG).550,618,626,650-652 Five thousand mg/L decreased feed intake and gain of cattle on a high roughage 

diet.653 Dairy cows given 2,040 mg/L water consumed 

less water and produced less milk when the peak ambient temperature was 32.1 C than cows given desalinated 

water.654 Similar decreases in milk production attributed 

to consuming saline water were seen in Arizona.547,655 

Swine subsisting on water containing 10,000-15,000 

mg/L drank less, ate less, and performed more poorly 

than controls.565 Sheep seem to be more tolerant of saline 

waters than most domestic species and will drink them 

if introduced to the saline water over a period of several 

weeks.540,541,575-580,656,657 The two references regarding 

saline waters in horses indicate they are reluctant to drink 

such water551, and it has been alluded they can be maintained on water containing up to 9,500 mg/L TDS.658 

Limited studies with farmed deer in Australia indicate 

TDS concentrations as high as 4,000-6,000 mg/L are tolerated without any reduction in feed or water consumption.659,660 We were unable to find any reports addressing 

the effects of salinity on wild deer.

Even when animals drink more in an attempt to compensate for poor water quality, the increased metabolic 

load imposed by high solute water may result in impaired 

performance. Water containing 1.5% NaCl (15,000 

ppm) and given to cattle for less than a week resulted in a 

13.7% reduction in weight, as well as decreasing feed and 

water-intake, and marked hypernatremia.550 In a similar, 

short-term experiment at cool temperatures, cattle given 

15,000 mg/L TDS water drank more, ate and grew less, 

and showed clinical signs of dehydration.558 Five-thousand mg/L TDS for 51 days decreased gain in heifers.651

Summary

Total dissolved solids in drinking water serves as a very 

poor predictor of animal health. As noted above, TDS is 

a measure of all inorganic and organic substances dissolved in water. These individual solutes range in toxicity 

from relatively non-toxic substances, such as Ca2+, to 

extremely toxic (Hg2+, Se+4), but tests of TDS do not 

differentiate between them. Several early studies suggest 

no significant effects in sheep at TDS concentrations up 

to 13,000 mg/L or cattle and swine up to 5,000 mg/L, 

and the NRC661 accepted larger concentrations as tolerable “for older ruminants and horses,” yet the authors 

have seen animals poisoned by waters in which the TDS 

was measured as slightly less than 500 mg/L,415,662 and 

there are reports of decreased productivity in dairy cattle 

at 2,000-2,500 mg/L. Early epidemiologic studies in 

people suggested high drinking water TDS decreased the 

incidence of cancer and heart disease in people. Later, 

however, studies narrowed the active component of TDS 

that was negatively correlated with heart disease, first to 

hardness, then finally to the Mg2+ ion concentration. In 

human health, the World Health Organization dropped 

health-based recommendations for TDS in 1993, instead retaining 1,000 mg/L as a secondary standard for 

“organoleptic purposes.” The test is just too non-specific to 

be reliable. As noted by Chapman et al.663, in a study of 

aquatic toxicity, “Toxicity related to these ions is due to 

the specific combination and concentration of ions and is 

not predictable from TDS concentrations.” 

We do not recommend relying upon TDS to evaluate 

water quality for livestock and wildlife; however, if no 

other information is available, TDS concentrations 

less than 500 mg/L should ensure safety from almost 

all inorganic constituents. Above 500 mg/L, the 

individual constituents contributing to TDS should be 

identified, quantified, and evaluated.
51

Element Short (days – weeks) 

Exposure

Chronic (months) 

Exposure

Rationale

Arsenic 1 mg/L 1 mg/L Does not seem to be a carcinogen in livestock; 

therefore, a concentration that protects against 

cytotoxic effects should be safe (pg 8).

Barium See text page 13 No recommendation Until there is better data we cannot make any firm 

recommendation regarding Barium. See text for 

interim suggestions (pg 13).

Fluoride 2 mg/L 2 mg/L Prevents dental lesions in most sensitive life stage. 

Fully mature animals may be able to tolerate more 

(pg 18).

Molybdenum 0.3 mg/L 0.3 mg/L Prevents secondary Cu deficiency and poor performance (pg 24).

Nitrate 500 mg/L 500 mg/L Prevents acute death and abortion in well-managed cattle. Dry diets high in NO3

 may require 

lower concentrations (pg 28).

Nitrite 100 mg/L 100 mg/L Prevents acute death and abortion in well-managed cattle. Dry diets high in NO3

 may require 

lower concentrations (pg 28).

pH No recommendation No recommendation There is considerable evidence that animals tolerate a much wider range than the commonly cited 

6.5-8.5, but we could not find sufficient information to make specific recommendations (pg 32).

Selenium 0.1 mg/L 0.1 mg/L Prevents selenosis in equidae. Can probably 

tolerate slightly high concentrations for very short 

periods (pg 38).

Sodium 4,000 mg/L 1,000 mg/L Assuming normal feedstuff Na concentration 

and no other water sources, these concentrations 

should protect against acute lethality or chronically, poor performance (pg 43).

Sulfate 1,800 mg/L 1,000 mg/L Assuming normal feedstuff S concentration, acute 

death may occur in ruminants at concentrations 

greater than 2,000, especially if not allowed time to 

acclimate. Long-term consumption result in poor 

performance (pg 47).

TDS No recommendation No recommendation We do not recommend relying upon TDS to 

evaluate water quality for livestock and wildlife 

(pg 50).

12 Summary
52
53

13 Research Needs

pH – The original acceptable range often cited in various extension and regulatory documents was designed to 

protect plumbing rather than health. Research suggests 

rodents and swine can not only tolerate but actually 

thrive on significantly lower pH activities than current 

standards. There is some indirect evidence from the dairy 

industry, where acidogenic diets have been used therapeutically, that cattle (and probably other ruminants) should 

perform well on moderately acidic water for months at 

a time. There is nothing to indicate what, if any, limits 

should be for long-term consumption. Nor is there any 

experimental evidence to indicate even the mild alkaline 

pH activity recommended under current guidelines, let 

alone stronger bases, are safe for animals. It might not be 

possible to devise a simple guideline that fits all situations 

as the acid-base status of mammals is very multi-factorial, 

but it should be possible to at least determine a range at 

which the direct, local effects of alkaline waters are likely 

to cause refusal.

Ba – The existing human guidelines are predicated upon 

the theoretical potential for the Ba2+ ion to exacerbate 

chronic cardiovascular problems. The existing knowledge 

base regarding Ba toxicity in livestock and wildlife is exceedingly scant and seemingly contradictory. If, as seems 

likely, large ungulates respond similarly to Ba as humans 

and rodents, toxicity could potentially occur at similar 

water concentrations. Large-scale, chronic experiments 

of the sort required to conclusively establish a chronic 

NOAEL will be very expensive. It might be more cost 

effective to elucidate the comparative toxicodynamics 

(bioavailability from various sources, pharmacokinetics, 

pharmacodynamics) of Ba in major livestock and wildlife 

species vs. rodents with an eye to extrapolating the large 

human/rodent database to these species. 

Wildlife – There is a surprising deficit of quantitative 

toxicologic data in big game wildlife species, especially 

when one considers the resources that have been lavished 

on fish and insects for the last three decades. Given the 

physiological similarities to domestic livestock, it should 

not be necessary to reinvent the complete knowledge 

base. Relatively simple comparative studies of basic toxicologic parameters such as bioavailability between (e.g.) 

mule deer and domestic sheep would allow extrapolation 

from the existing knowledge base in livestock to wildlife.

Nitrite – While there is substantial anecdotal evidence 

NO2 is more toxic than NO3, especially in non-ruminants, we didn’t find a great deal of quantitative doseresponse data about oral exposure in livestock or wildlife. 

What we did find suggests a maximum tolerated dose 

considerably higher than the NRC.2 The latter recommended keeping NO2

 extra low to compensate for NO2

formation in slurried feedstuffs to swine. This practice is 

no longer common, nor is the caveat appropriate to range 

conditions. A reliable maximum tolerated dose, appropriate to Western range conditions, is desirable.
54
55

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