Performing toxicant exposure assessments: A clinical step in effective case management (Proceedings)

Concentration basics

Units of concentration can refer to a concentration in a liquid or solid material.  If in a liquid, the concentration units are typically expressed as a weight per volume (e.g., microgram/mL, microgram/L, mg/L, mg/dL, mg/mL).  If expressed in a solid, the concentrations are typically expressed as a weight per weight (micrograms/mg, micrograms/Kg, mg/Kg, mg/g).  Concentration units representing the proportion of toxicant in the total product are common and include %, milligram percentage (mg%), parts per million (ppm), parts per billion (ppb), etc.  The concentration unit ppm is equivalent to mg/kg for solids or mg/L for liquids.  If mg/kg or mg/L are divided by 1000 the equivalent units would be micrograms/g or micrograms/mL, respectively.  The concentration unit ppb is the same as micrograms/kg or micrograms/L.

Conversions from % to ppm

One % equals 1 gram in 100 grams for solids or 1 g/100 mL for liquids.   1 gram/100 mL = 1000 mg/100 mL = 10,000 mg/1,000 mL = 10,000 mg/L = 10,000 ppm.  Therefore 1% equals 10,000 ppm.  One rule of thumb is to move the decimal point four places to the right to convert percentage to ppm (e.g., 0.04% = 400 ppm; 2.5% = 25,000 ppm).  The reverse can be done to convert ppm into %.

Exposure calculations

Exposure calculations are necessary to determine the dose of a toxicant an animal has potentially ingested and whether decontamination interventions (e.g., emetics, activated charcoal, etc.) are needed or other possible treatments likely to be needed.  The other time an exposure calculation is needed is when an animal is showing clinical signs and one wishes to rule out a specific toxicant as a cause.  Exposure calculations require several pieces of information: 1) the toxicant concentration in a product, bait, or feed, 2) the amount of product, bait, or feed ingested, and 3) the weight of the animal(s).   If all of these pieces of information are known the following formula can be used to calculate an exposure:

mg/kg body weight exposure = concentration of toxicant in product/bait/feed x amount of product/bait/feed ingested ÷ kg body weight.

The units wind up to be similar to a drug dosage (i.e., mg/kg).  Once the toxicant dosage is determined, it can be compared to a measure of the toxicity of the chemical and allow for the determination of the severity of the exposure.   For the majority of toxicants, the most common measure of toxicity is the lethal dose 50 (LD50).  Conservative advice would be to treat exposures within five- to ten-fold of an LD50 determined in a species of interest as potentially significant.  This is a rough rule of thumb for which there can be exceptions.  Unfortunately, toxicity data is often unavailable for a given toxicant in a species of interest (e.g., dog or cat).  Measures of toxicity are often available only in rodent or other experimental species.  A safety factor of 10 is often applied when extrapolating toxicity data from one species, most often rats or mice, to another species such as dogs, cats, or humans.

Calculating exposure from baits

It is necessary to estimate the amount of bait ingested in order to calculate exposure.  In many cases this information is not available.  In such situations, a conservative approach would be to assume that the entire contents of a bait package (if available) were consumed.  For example, if an unknown amount of bait from a package containing 50 grams of material was eaten by a dog one should assume that the entire contents had been ingested.  If the results of the exposure calculation indicated that a non-toxic amount of material was ingested, then no treatment would be necessary.   Often it is necessary to convert ounces of bait to grams for solid materials or mL for liquid baits.  One ounce equals approximately 30 grams.  There are two steps involved in the exposure calculation.  The first step is to calculate how many mg of toxicant were ingested based upon the amount known to be or potentially known to be available and the concentration of the toxicant in the bait:

• Concentration (mg/g, mg/ml, mg/kg, or mg/L) x amount of bait consumed = mg of toxicant consumed.

• Step 2 is to calculate the actual exposure in the animal by dividing the mg of toxicant consumed by the animal's body weight:

• mg of toxicant ÷ kg body weight = toxicant exposure in mg/kg body weight

This calculated value is then compared to a measure of toxicity in the species of interest or another species.

Exposure calculation examples

Case one

A 75 pound Yellow Labrador ingested a 1/2 pound bag of Hershey's Kisses (foil and all) one hour ago.  The owner calls to ask if the dog should be brought to the clinic for treatment.   You quickly consult your toxicology text and find out that Hershey's Kisses contain 50 mg of theobromine and 10 mg of caffeine per ounce.  A combined minimum toxic dose of theobromine and caffeine for a dog is as low as 100 mg/kg.  What was the dosage (mg/kg body weight) that the dog ingested? 

Case two

An owner has come home to find that her two dogs (“Polly”, a 2 year old, 25# mix and “Shelly”, a 3 year old, 65# Lab) have ingested up to 50 regular strength NuprinR tablets (200 mg ibuprofen).  The owner reports that both dogs appear normal.

Case three

Buster, an 8.9 kg, neutered male Fox Terrier was referred to you for possible rodenticide exposure.  The owner's son had rats in the household that escaped and started breeding.  He placed two different types of rat poison around the property (D-con® containing 0.005% brodifacoum and Fastrac® All Weather Blox containing bromethalin at 0.01%).  At presentation, Buster has a body temperature of 94.7 F, pulse of 160 beats per minute with weak femoral pulses, respiratory rate of 48, and “white” mucus membrane appearance.  The owner reports that the dog has been lethargic and not eating for 48 hours.  Ultrasound was consistent with a moderate pleural effusion and mild pericardial effusion.  Given the two toxicants that might have been accessible to Buster, you look up in your toxicology references how toxic they are and find minimum lethal doses of 1 mg/kg body weight for brodifacoum and 2 mg/kg body weight for bromethalin. 

Additional reading

DeClementi, C. (2011):  Essential calculations.  In: Poppenga, R.H. and Gwaltney-Brant, S.H. (eds) Small Animal Toxicology Essentials, Wiley-Blackwell, Ames, IA, pp. 33-42.

Blodgett, D.J. (2002):  How to evaluate toxicant exposures.  Vet Clinics North Amer: Small Animal Practice, 32(2): 341-356.