Sir James Dunn
Animal Welfare Center
TOXIC DOSE CALCULATIONS
Veterinarians frequently receive calls from animal owners asking if a particular substance is toxic or harmful to their animal. “My dog just ate one of my baclofen pills. Is this going to poison her?”; “My cat ate some Christmas cactus plant. Can this cause any problems?”; “My dog got into some slug bait. Do I need to bring him in for treatment?”. The only way to answer these questions appropriately is to know exactly what the animal was exposed to (ie, what chemical or substance), how much the animal was exposed to, and the circumstances – ie, route of exposure, species of animal involved and other patient characteristics. This newsletter will focus on how much – ie, how to calculate toxin exposure doses and how to use toxic dosage information.
The most basic tenet of toxicology is “the dose makes the toxin”. Virtually all substances are toxic if given at a high enough dose. Conversely, most substances are safe if given at a low enough dose. For example, ingestion of one 45-gram milk-chocolate candy bar will not be a problem for a 75 lb Labrador Retriever. However, ingestion of 35 of these candy bars could potentially be lethal to this dog. Knowing the dose of a particular toxin that an animal has received will help determine how aggressive treatment needs to be and what level of treatment risk is acceptable.
In many cases, calculation of exposure dose of the toxicant is unnecessary or even impossible. For example, if an animal presents with a history of exposure to a particular toxin, has clinical signs consistent with that toxin, and diagnostic test results support the diagnosis, there is generally no need to calculate the dose of toxin the animal received. Obviously, the animal received enough of the toxin to cause poisoning and treatment is required. Additionally, many animals present with signs consistent with intoxication but actual exposure was not witnessed. In these cases, exposure dose calculations are not possible.
there are times when exposure dose calculations for a particular toxic
substance are possible and can be very helpful. For example, when
recent exposure to a known toxin has been witnessed, it is very useful
to know if the exposure amount was enough to potentially cause
poisoning and hence warrant decontamination and treatment. If the
exposure dose was high enough to be potentially lethal, this will
indicate that aggressive treatment is appropriate as the animal may
otherwise die. By knowing how to calculate exposure dose and how to use
toxic dosage information, you can greatly improve your ability to
appropriately handle poison cases.
EXPRESSIONS OF TOXIN CONCENTRATION
of toxin in a substance can be expressed in a variety of ways. These
Most published toxicity data pertaining to toxic dosages for animals is expressed as mg of toxicant per kg of animal body weight. Ingredient concentrations and package weights are often expressed for commercial purposes in the English system of ounces and pounds. Toxicity data in text books and other sources can be expressed using either the metric or the English system. Therefore, you need to be able to convert readily between the various ways of expressing toxin concentrations and between metric and English equivalents. Following are some guidelines to help with calculations and conversions:
Common metric terms:
Common conversions between metric and English equivalents (approximations):
1 ounce =
convert ppm to mg/kg: 1 ppm = 1 mg/kg
Similarly, 1 ppb = 1 µg/kg
convert ppm to mg/l: 1 ppm = 1
Similarly, 1 ppb = 1 µg/liter
convert ppm to percent (%): 1 ppm = 0.0001%
of thumb: to convert ppm to percent, move
the decimal point 4 places to the left. To convert percent
to ppm, move the decimal point 4 places to the right. You can
easily remember which way to move the decimal point because ppm
is always larger than %.
convert % of a liquid chemical in a liquid medium to volume/volume: % = ml/100 ml
convert % of a solid chemical in a solid medium to weight/weight: %
= grams/100 grams
convert % of a solid chemical in a liquid to weight/volume: %
= gram/100 ml
TOXIC DOSAGE INFORMATION
Toxic dosage information can be expressed a number of ways. Common values include median lethal dose (LD50), lethal dose (LD), minimum lethal dose (LD), toxic dose low (TDL), minimum toxic dose or maximum tolerated dose (MTD), and no observed adverse effect level (NOAEL). These values are very species-specific – i.e., the LD50 value for a particular toxin for a rat may be dramatically different than that for a horse or a cat. Therefore, you need to find information pertaining specifically to the species you are dealing with. The toxic dosage information of most use to you as a veterinarian is the minimum toxic dose (i.e., the lowest dose at which you expect to see clinical signs), and the minimum lethal dose (the lowest dose at which death occurs). LD50 is generally not as useful for clinical cases of poisoning, as this value only tells you the dose at which 50% of a subset of research animals of a specific species under experimental conditions will die. It tells you nothing about the dose at which the first animal died.
Toxic dosage information can be found in a number of places. The most common source of information is a good veterinary toxicology textbook. Two excellent small animal toxicology textbooks include Small Animal Toxicology by Peterson and Talcott (W.B. Saunders Co, 2006) and the Handbook of Small Animal Toxicology and Poisonings by Gfeller and Messonnier (Mosby Inc, 2004).
Unfortunately, many exposures involve drugs or products for which toxic dosage information is not available in standard veterinary toxicology textbooks. In these cases, information can often be found using toxicological information sites on the Internet (see the "Toxicological Information Sources" newsletter for more information on useful websites). Even if specific values for minimum toxic dose and minimum lethal dose are not published, often you will find information that will give you a ballpark idea of these values. If the information you need cannot be readily found in textbooks or on the internet, the ASPCA Animal Poison Control Center (APCC) can often provide you with toxic dosage information as well as treatment recommendations (see the Toxicological Information Sources newsletter).
that many factors can influence the toxicity of a given substance.
Patient characteristics that can influence dosage necessary to cause
intoxication include species, age, sex, nutritional status,
reproductive status, genetic differences, concurrent disease, and
concurrent exposure to other drugs or toxins. Factors such as route of
exposure (oral, dermal, or inhalation), frequency of exposure, and
characteristics of the toxicant (formulation, valence state, vehicle,
etc.) can also dramatically influence toxicity. Be sure to take these
into consideration when interpreting toxic dosage information. Also
remember that the toxic dose information you require may not
be available. This is frequently the case with new human drugs
or new consumer products. In such cases, you should assume that the
animal has been exposed to a dose sufficient to cause harm or even
EXAMPLE: TOXIC DOSAGE CALCULATION
A pet owner calls and says he just found his dog eating rat poison he put under the refrigerator. He does not know how the bait got out from under the frig. The rat poison originally came in a box that contained a number of little paper pouches (place packs). He had placed 2 of the pouches under the refrigerator and 2 under the kitchen sink. The rest are stored in a cupboard in the garage where the dog is never allowed. He thinks the dog has eaten about ˝ of one pouch. You ask him if he knows the name of the poison. He can just make out the words, “Quintox rat...(the paper is torn here)... bait pac..” on the paper pouch. He can have the dog to your clinic within 5 minutes. You instruct him to bring the dog in immediately so that you can initiate decontamination procedures and treatment if necessary. You request that he bring in the remains of the half-eaten package as well the other packets he put out and the box containing the unused packs. This way you can better determine how much poison the dog ingested (ie, did he ingest the other pouches under the frig and sink unbeknownst to the owner) and verify the active ingredient and concentration.
You now do
an internet search of the Canadian Pesticides website (see Newsletter
#1), and quickly find that Quintox Rat and Mouse Bait Pacs contain 50
ready-to-use place packs, each weighing 30 grams. You see that
this bait contains 0.075% cholecalciferol. Now that
you know the active ingredient, you look up cholecalciferol in your
small animal toxicology textbook. You find the following:
The dog arrives at your clinic shortly thereafter. He is an adult intact male Golden Retriever, weighing 80 pounds. The dog appears to be healthy and normal on physical examination, he has no history of any major medical conditions, and is not receiving any drugs. You see from the box of rat poison that the owner brings with him that the poison is indeed cholecalciferol 0.075%, and that each of the 50 place packs weighs 30 grams. The owner found intact the other 3 place packs he had put out, and 46 pacs remain in the box. Only 1/2 of one packet was ingested.
Approximately how many mg of cholecalciferol per kg of body weight did
this dog ingest?
also be calculated as follows: 0.075 % = 0.00075
(2) This dog weighs 80 lbs x 0.45 kg/lb = 36 kg
(3) The dosage of cholecalciferol this dog ingested was 11.25 mg/36 kg or 0.312 mg/kg
What is the estimated toxic dosage (ie, mg/kg) of
cholecalciferol for this dog?
Did this dog ingest enough cholecalciferol to warrant treatment?
What is the estimated lethal dosage of
cholecalciferol for this dog?
Another way to do these calculations is to calculate the actual number
of mg of toxin the dog ingested, and compare that to
how many mg of toxin would be required to cause
intoxication or death. For example: