Basic Hazards

Dose

Routes of Entry

Effects

Local vs Systemic

Measures

Classification

Measures of Toxic Effect

The inherent toxicity of a substance is one of the factors that determines how a material should be handled in the laboratory. Substances may be acutely toxic, chronically toxic, or both.

Acute toxic effects (those that occur after a single exposure) of substances are typically measured in animals (rats and mice) and defined in terms of the lethal dose 50 (LD50) or lethal concentration 50 (LC50). The LD50 is defined as the amount of chemical that when ingested, injected, or applied to the skin of a test animal, will be lethal to fifty percent of the test population. The LD50 is typically expressed in milligrams of test substance per kilogram of body weight. The lethal dose of highly volatile chemicals is typically expressed as the airborne concentration that will be lethal to fifty percent of the test population (LC50). The LC50 is typically reported as an airborne concentration (parts per million, mg per cubic meter, etc.) over a specified time period (example: 10 ppm; 4 hours).

Some acute toxicity studies also report LDlo and LClo values. These are defined as the lowest dose or concentration that were lethal in the test animal population.

Measurement of Acute Toxicity
Classification LD50-Wt/Kg
Single Oral Dose
Rat
LC50-PPM
4 Hr Inhalation
Rat
Extremely Toxic 5-50 mg or less<10
Highly Toxic 5-50mg 1-100
Moderately Toxic 50-500 mg 100-1,000
Slightly Toxic 0.5-5grams, 1,000-10,000
Practically Non-toxic 5-15 grams 10,000-100,000
Relatively Harmless 15 grams or more >100,000

The lower the value of the LD50 and LC50 the more toxic the substance. Although the lethal dose varies between test animal species and animals and humans, the relative toxicity of substances is usually constant. Therefore a highly toxic substance in an animal model is likely to be highly toxic to humans.

The potential for a substance to cause chronic health effects (such as target organ, cancer or reproductive effects) can be studied in human populations (epidemiology studies), animal test populations, or in some cases specific cell lines. Studies report the dose rate (milligrams of test substance per kilogram of body weight per day) that caused adverse health effects and/or the "no observed effect level" (NOEL) which is that dose at which no adverse health effect was observed. Materials that have been identified as causing chronic health effects should be handled in a manner that minimizes exposure. Specific guidance is given in the reference section 'Special handling and use requirements - toxic chemicals'.

Several organizations such as National Toxicology Program, International Agency for Research on Cancer, regularly report lists of chemicals known or reasonably anticipated to have severe chronic health effects. The OEHS maintains these lists on their web site (www.yale.edu/oehs).