Students have asked several times, "Why is that permitted?" "Don't all chemicals have to be tested?" and similar questions. Here I will try to answer that. First, here's a site from another course. The first page and half is pertinent to today's module. Introduction to Laws.

Here's a quote about the difference between the goals of science and the goals of government:

Government regulators are often forced to intervene, and make a decision before knowledge is complete. American regulation is bound up in the concept of "rule of law." Rather than a private negotiation between interested and affected parties that characterizes rule-making in many industrial countries, American regulation must make rules based on the legislative intent and must explain the reasons or facts that form a basis for these rules. This allows opponents of the rules numerous opportunities to contest facts. Often the facts are weak and both sides have great opportunities to construe what facts there are in a manner suitable to their case. This forces the regulators to defend their decisions based on the weak facts and sometimes "distort the current knowledge," often by putting more weight on evidence that the underlying science can bear.

"The statute laws often describe a desirable social outcome, and may demand more of science that it can provide." [Material above and quotes from the Regulatory Toxicology chapter by Richard Merill in Casarett and Doull's Toxicology.]

Government agencies often publish "guidance documents." These are a two edged sword. They are often a consensus standard put together by experts in the field and provide minimum standards for many investigations. However they also limit innovation and may not be the best test method for any particular situation. Since the guidance documents are not law, other reasonable procedures may be substituted but, as a practical matter, the standard methods are often really a requirement, rather than guidance.

A vital concept in regulatory toxicity is that of "burden of proof." Who has the responsibly for demonstrating a substance is harmful or safe? This is established by the statute. For example, for food additives, the manufactures must prove they are safe before they are put in food. On the other hand, for occupational exposures, OSHA must demonstrate that a substance is harmful before its use is restricted.

Carcinogen versus Non-Carcinogen
You have already learned that there is a difference in the regulation of carcinogens versus non-carcinogens. Non-carcinogens are assumed to have some dose, below which they will not cause harm. That dose might be called the Acceptable Daily Intake (aka "reference dose," "RfD"), which we would call a threshold. Carcinogens are usually assumed to have no threshold, although that view has changed somewhat in recent years.

Risk Allowed
Some laws specify no risk is allowed. For example, any chemical that causes cancer in laboratory animals is not permitted as a food additive. Other laws and regulations will permit a negligible risk, for example a 1 in one million increase in cancer rate is considered negligible. There are also tradeoff approaches. These often use the word "feasible," which implies risk is permitted, if it is economically impractical to remove or reduce the risk.

There are 4 main U.S. Federal agencies that are responsible for regulating human exposure to chemicals:

• FDA, the Food and Drug Administration
• EPA, the Environmental Protection Agency
• OSHA, the Occupational Safety and Health Administration
• CPSC, the Consumer Product Safety Commission.

Food and Drug Administration (FDA)

The FDA administers the Food, Drug, and Cosmetic Act (FD&CA). Let's look at each of those in turn:

Food
A food may not be marketed if it has an additive, which "may render it injurious to health." To add a new additive today, a manufacturer must test the additive to FDA specifications and show it is "reasonably certain to be safe." A great exception was made however for additives, generally recognized as safe (GRAS) or ingredients that were in use prior to 1958. The "Delaney Clause," a section of the 1958 act, prohibits chemicals that cause cancer in laboratory animals from being approved. Three other classes of food chemicals are regulated separately: pesticide residues, animal drug residues, and food contact materials (packaging) residues. Here is a problem. With analytical chemistry tools much more exact then they were in 1958, small quantities of chemicals that, at high doses, can cause cancer, are often found in foods, usually due to pesticides or packaging. The Delaney Clause would seem to prohibit these, but clearly they are not added purposefully to the food. The FDA uses a negligible risk rule for these substances, rather than a no risk.

Human Drugs
The FDA has stringent regulations for drugs. The regulations focus on the "clinical trials" of the drug, when it is given first to human volunteers, then to experimental patients, finally to general, but closely observed, use. Prior to the clinical trials, the drug must go through preclinical testing. Animal studies and testing are used to determine the basic safety of the drug and also its doses. Long term animal testing is also required for many drugs. As a practical matter, all pharmaceutical companies thoroughly test their proposed drugs for toxicity. Presumably they know a great deal about the chemical and are able to decide upon relevant testing. Thalidomide and DES were tragic blunders, but both involved pregnancy. Today any drug for use during pregnancy is subject to stringent multi-generational testing. On the other hand, the new drug does not have to be very effective, nor even more effective than drugs that are already on the market. All the pharmaceutical company has to show is that the drug is of some benefit in treating the condition. Since the FDA holds a big hammer over the drug companies, the FDA can demand about anything in preclinical tests. One thing that has come from that is the concept of Good Laboratory Practice (GLP). These are fundamental quality control procedures that laboratories whose work will be subject to FDA approval must meet.

Cosmetics
No product may be marketed if it contains "a poisonous or deleterious substance which may render it injurious to health." While this implies pre-market studies, they are not in-fact required for most ingredients. Color additives however must be tested, similar to food additives. Look at the label of your favorite cosmetic. You will probably see FD&C red dye number X,or whatever. This specifies that the particular color has been approved, subject to that act. Shampoo in confidence.

Environmental Protection Agency (EPA)

Pesticides
FIFRA (Federal Insecticide, Fungicide, and Rodenticide) was mentioned earlier. It requires "registration" of pesticides with the EPA. The EPA must assure that"when properly used...will not generally cause unreasonable adverse effects on the environment." Later congress amplified what that meant, "any unreasonable risk to man or the environment, taking into account the economic, social and environmental costs and benefits of the use of any pesticide." So clearly a tradeoff approach is required. Talk about tradeoffs, I'll bet your getting bored with reading this stuff. Go to the Blackboard site > Course Documents> Special Documents, and pull down the pdf file about Pirate. It is a brief article from 1999. In 2001, EPA withdrew the approval for Pirate for cotton, but only approved it for greenhouse use for non-food crops.

Chemicals
TSCA, Toxic Substances Control Act, would seem to be what you are looking for, especially if you are an out-of-work toxicologist. It applies to all chemical substances"manufactured or processed or imported into the United States." The only exception is chemicals that are already regulated by other laws. EPA may restrict, including "banning the manufacture, processing, distribution, use or disposal of a chemical substance...when there is an unreasonable risk of injury to health or the environment." However, and you knew this was coming, the EPA can only demand testing, if it suspects that the chemical may pose an unreasonable risk. If a product has been in use, but has not caused problems, the EPA is in weak position to demand testing. Manufacturers or importers of a new chemical must notify EPA about the chemicals and submit any data on its hazards that they happen to have, but the EPA is not empowered to require testing. So TSCA, despite its intent, does not require toxicity testing, except in special circumstances, typically when EPA has reason to believe a substance is dangerous. It is well to remember that this concept of hazards is related to the intended use of the chemical. There are many extremely hazardous and toxic materials used in industry, but their intended use does not expose humans or the environment. Take methyl isocyanate (MIC), the toxic agent at Bhopal, India, that killed many people. Here, read all about it. Bhopal . MIC is still made in the USA. Enough said.

Hazardous Wastes
We talked about the two main hazardous waste laws, CERCLA and RCRA, in an earlier module. We'll discuss them more in 12B. The RCRA definition of hazardous waste, [a substance that may] a) cause, or significantly contribute to, an increase in mortality or an increase in serious irreversible, or incapacitating reversible, illness; or (b) pose a substantial present or potential hazard to human health or to the environment when improperly treated, stored, transported, or disposed of...."

Toxic Water Pollutants
The Clean Water Act required the EPA to establish a list of toxic pollutants and establish standards for their discharge. The definition of "toxic pollutant" says "after discharge and upon exposure, ingestion, inhalation assimilation into any organism, either directly from the environment or indirectly ...through food chains, will on the basis of information available to [EPA] cause death, disease, behavioral abnormalities, cancer, genetic mutations, physiology malfunctions....organisms or their offspring." Further, the standards set were to provide an "ample margin of safety." Clearly a very broad mandate. Note this is for any organism, not just humans. This law has been subject to many lawsuits and regulatory gyrations. The language is broad enough to condemn almost any chemical, but, note also the underlined words, it does not require testing. The hammer that EPA holds is that an industry or government cannot get a permit to discharge into the water, if the discharge contains toxic pollutants above a level that provides the ample margin of safety. But you realize that this relates to the "dose" to organisms. What is the dose that provides this margin of safety? Also, where do you measure the dose? At the end of the discharge pipe? At the other side of the lake? And how about if this discharge has very low concentrations of pollutants, but other existing industries have been loading the water body with it?

Drinking Water
The Safe Drinking Water Act applies to public drinking water supplies and requires the EPA to regulate any contaminant "which may have an adverse effect on human health." Here the EPA set regulatory standards for chemicals.

Toxic Air Pollutants
The Clean Air Act requires the EPA to publish a list of pollutants that "cause or contribute to air pollution which may reasonably be anticipated to result in an increase in mortality or an increase in serious irreversible, or incapacitating reversible illness." The EPA then must promulgate standards that provide for an "ample margin of safety."

Occupational Safety and Health Administration (OSHA)

The Occupation Safety and Health Act requires OSHA to adopt standards "which most adequately assure, to the extent feasible, on the basis of the best available evidence, that no employee will suffer material impairment of health or physical capacity." OSHA lacks the regulatory authority to require employers to test chemicals, so OSHA must rely on data collected elsewhere. OSHA has a parallel agency, NIOSH (National Institute of Occupational Safety and Health), which resides in a different branch of the government, the Public Health Service (OSHA resides in the Department of Labor). NIOSH is empowered to test chemicals, and does. NIOSH is not well funded, however, and most of their efforts go towards chemicals that are already known as hazards. It is important to realize that OSHA's authority is limited to requiring employers to protect the health of their employees. In a school, OSHA could require the school district to provide safety features for the teachers or janitors, but OSHA could not require the district to protect the pupils.

Consumer Product Safety Commission (CPSC)

We started out this course by looking up the legal definition of "highly toxic" in the Consumer Product Safety Law. Now we've come a full circle. The CPSC really has a very limited mandate, to provide consumer warnings, primarily in the form of labels, and to ban certain consumer products that are unreasonably dangerous. The CPSA and related acts do not obligate manufactures to notify the commission of plans to market a new product or to obtain approval for any design or materials.

So there you have it. Lots of language that would seem to protect the public, but lots of loopholes and administrative bars to requiring toxicity testing of chemicals. Of the 30,000 or so chemicals in high use, less than 1,000 have been tested to any extent. Most of the 300,000 commercial chemicals and their myriad mixtures have not been tested. Before you buy a gas mask and charcoal water filter, most of the chemicals that are likely to cause problems based on their potential for human exposure have been tested. Most manufactures of chemicals perform some testing of chemicals for industrial use, and all chemicals for human consumption or use are tested as well. It is likely that most gross effects of these common chemicals at high doses are known with reasonable certitude. When it comes to regulation, however, the regulations must establish a "bright line," that is a level of chemical, below which is legal and above which is illegal. That is the region, even for the known chemicals, that there is tremendous scientific uncertainty.

Module 12 Index