safety factor

(electricity) The amount of load, above the normal operating rating, that a device can handle without failure.
(mechanics) factor of safety
(ordnance) Increase in range or elevation that must be set on a gun so that friendly troops, over whose heads fire is to be delivered, will not be endangered. Overload factor in design to ensure safe operation.

Safety factors have been used to protect the public health since the advent of modern safety assessment. Originally based on very little experimental data, the concept of safety factors was based on the premise that humans are more sensitive to chemicals and environmental agents than the most sensitive laboratory animal. By the time of World War I, experimental evidence with laboratory animals was being directly compared with findings in humans. It was evident that the original premise had little basis in fact, but was still a prudent approach for public health. As novel organic molecules were being developed as drugs and insecticides in the 1930s and 1940s, the concept of safety factors gave scientists and regulators some comfort that the public was being protected. Actual data on safety factors is still incomplete.

For many highly toxic compounds, humans are almost identical to laboratory animals in sensitivity. However, there are startling examples, such as thalidomide and some retinoic acid analogs, where humans are much more sensitive than laboratory animals. Several attempts have been made to quantify the physiological and toxicological differences across species. For the basic physiological systems that are essential for all mammalian species, the responses to many classes of chemicals, drugs, and physical agents are similar.

The basic assumptions underlying the use of safety factors is that by using these factors the public health is protected and special populations are also protected. Further assumptions hold that humans are somewhere between 10 and 1,000 times more sensitive to some toxic agents than are animals, adults are less sensitive than children, and the aged are more sensitive than younger individuals. Hence, a safety assessment can be conducted using the proper toxicological evaluation with multiple species of animals to establish the NOEL (no observable effect level) or its equivalent. The assessor can then use safety factors for species to species extrapolation (usually a factor of ten or more), which involves multiplying the NOEL by a tenfold factor for age differences, and perhaps a tenfold factor for special populations. Hypothetically if a NOEL established for Chemical A at 1,000 milligrams per kilogram body weight of the laboratory rat per day, the assessor could compute the safety factors and conclude that a safe dose would be 1 milligram per kilogram per day.

This is a simple case, and many other variables can be added. For an occupational exposure one might add a factor for hours worked compared to hours used in the tests. For an immunotoxic agent there might be a greater safety factor used for species or age comparison, particularly if children or the aged are exposed. The uncertainties surrounding testing for adverse birth outcomes usually result in the use of greater safety factors.

The rationale for additional safety factors for children has evolved over several years. Originally, children were looked on as small adults and their physiological differences, especially the rapid development and remarkable tissue and organ systems changes of children, were not given as much as attention as necessary. Recently, the emphasis has been on understanding how seemingly modest or small changes in a developing system can permanently alter that system when it matures. Greater care is now going into using safety factors for children. More basic research is still necessary to protect children, and until that work is completed the prudent approach has been to increase the safety factors for children.

Safety factors are widely used by regulators throughout the world. Some countries use safety factors for assessing the exposures to some carcinogens. The United States generally uses a quantitative risk assessment (QRA) approach to carcinogens, but uses a modification of the original safety factor approach for most other toxic endpoints. Safety factors were used exclusively until the late 1960s and early 1970s when the QRA methodologies were developed. The U.S. National Academy of Sciences/National Research Council has, through its many studies on drinking water, food additives, and others types of chemicals, published a rich history of the rationale and use of safety factors.

(SEE ALSO: Environmental Determinants of Health; Risk Assessment, Risk Management; Safety Assessment; Toxicology)

— MICHAEL GALLO