Sir James Dunn Animal Welfare Center
Improving the Care of Poisoned Animals

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.

However, 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.
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EXPRESSIONS OF TOXIN CONCENTRATION

The amount of toxin in a substance can be expressed in a variety of ways. These include:
(1) Weight/weight. Example: mg/kg, or mg of toxin per kg of substance containing the toxin
(2) Weight/volume. Example: mg/ml, or mg of toxin per ml of substance containing the toxin
(3) Proportion of toxin to total substance. Examples: % (% toxin); ppm (part per million, or 1 part toxin per 1 million parts of substance containing the toxin); ppb (part per billion)

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:

Unit
Abbreviation
Equivalent
kilo
k
103 (1,000)
gram
g
1 (1)
milli
m
10-3 (0.001)
micro
µ
10-6 (0.000001)



1 mg = 1,000
µg 1 g = 1,000 mg
1 kg = 1,000 g

Common conversions between metric and English equivalents (approximations):

1 ounce = 28 grams
1 pound = 0.45 kilograms
1 ton (short) = 0.9 metric tons
1 teaspoon = 5 milliliters
1 tablespoon = 15 milliliters
1 cup = 0.24 liters
1 fluid ounce = 30 milliliters
1 quart = 0.95 liters
1 US gallon = 3.8 liters
1 Canadian (Imp) gallon = 4.5 liters
1 ml of water has a mass of 1 gram (often extrapolated to other liquids)
1 pint of water = 1 pound (“a pint is a pound, the world around”)

Common toxin concentration conversions and formulas:

1. To convert ppm to mg/kg: 1 ppm = 1 mg/kg
1 ppm = 1 part per 1 million parts. The “parts” can be in any unit. So:
1 ppm = 1 g / 1,000,000 g = 0.000001
And: 1 mg/kg = 0.001 g /1,000g = 0.000001
Example: 50 ppm of a toxicant = 50 mg of toxicant per kg of total substance
(for example, 50 mg of toxicant per kg of feed).

Similarly, 1 ppb = 1 µg/kg
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2. To convert ppm to mg/l: 1 ppm = 1 mg/liter
This is based on the idea that 1 ml of water weighs 1 gram (therefore 1 liter weighs 1 kg)
Example: 10 ppm = 10 mg of toxicant per liter of total fluid

Similarly, 1 ppb = 1 µg/liter
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3. To convert ppm to percent (%): 1 ppm = 0.0001%
1 ppm = 1 part /1,000,000 parts; 1 / 1,000,000 = 0.000001; 0.000001 = 0.0001%
1 percent = 1 part per 100 total parts.

Rule 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 %.
Examples: 1,000,000 ppm = 100 %
10,000 ppm = 1 %
100 ppm = 0.01 %
1 ppm = 0.0001 %
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4. To convert % of a liquid chemical in a liquid medium to volume/volume: % = ml/100 ml
Example: ethanol 95% = 95 ml of ethanol per 100 ml of total solution
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5. To convert % of a solid chemical in a solid medium to weight/weight: % = grams/100 grams
Example: cholecalciferol 0.075% = 0.075 grams of cholecalciferol per 100 grams of bait
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6. To convert % of a solid chemical in a liquid to weight/volume: % = gram/100 ml
Once again, this is based on the idea that 1 ml water weighs 1 gram (therefore, 100 ml of water weighs 100 grams).
Example: lidocaine 2% = 2 grams of lidocaine per 100 ml of total solution.
This can be converted to mg/ml: (2 g/100 ml) x (1,000 mg/g) = 20 mg/ml
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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).

Remember 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 death.
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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 single oral lethal dose of cholecalciferol (vitamin D3) in a mature dog is about 13 mg/kg. A dose as low as 2 mg/kg has been reported to be toxic in dogs. In general, puppies are more sensitive to vitamin D toxicosis than are adults”.

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.

A. Approximately how many mg of cholecalciferol per kg of body weight did this dog ingest?
(1) 30 grams of bait per pack x 0.5 packs = 15 grams of bait ingested
The bait contains 0.075% cholecalciferol = 0.075 gram cholecalciferol per 100 grams bait
0.075 grams cholecalciferol/100 grams bait x 15 grams of bait ingested
= 0.01125 grams of cholecalciferol was ingested.
Now convert this to mg:
0.01125 grams cholecalciferol x 1000 mg/gram = 11.25 mg cholecalciferol ingested

(This can also be calculated as follows: 0.075 % = 0.00075
0.00075 x 15 grams bait x 1000mg/gram = 11.25 mg cholecalciferol)

(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

B. What is the estimated toxic dosage (ie, mg/kg) of cholecalciferol for this dog?
The toxicology textbook stated that “ A dose as low as 2 mg/kg has been reported to be toxic in dogs”.

C. Did this dog ingest enough cholecalciferol to warrant treatment?
The dog ingested 0.312 mg/kg of cholecalciferol, which is well below the reported minimum toxic dose of 2 mg/kg. If the dog is healthy and alert and no contraindications exist, decontamination via induction of emesis and administration of activated charcoal should be performed to further diminish the amount of toxin absorbed by the dog. With the low exposure dose and further reduction via decontamination, clinical signs of intoxication are unlikely to occur and other treatments such as calcitonin, pamidronate, etc. will likely be unnecessary.

D. What is the estimated lethal dosage of cholecalciferol for this dog?
The textbook stated “The single oral lethal dose of cholecalciferol (vitamin D3) in a mature dog is about 13 mg/kg”. This is 40X more than the dosage the dog ingested. Therefore, it is highly unlikely that the dog will die from this exposure even if no decontamination or treatment is performed.

E. 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:
– From part A, we see that the dog ingested 11.25 mg of cholecalciferol
– From part B, we can calculate how many mg of cholecalciferol would cause intoxication:
2 mg cholecalciferol/kg body wt x 36 kg = 72 mg of cholecalciferol would cause intoxication.
– Therefore, the dog ingested only about 1/6 of the minimum toxic dose.