Boric Acid, Part II By Michael R. Cartwright, Sr.

Part I of Mr. Cartwright's article addressed the use of Boric Acid (the main ingredient in many flea control products such as Fleabusters) in a method that is inconsistent with that recom- mended by the manufacturer -- i.e. broadcast application, or spreading over a large area where there will be constant direct contact. This type of application can lead to exposure to the chemical which can have harmful effects. Particularly susceptible would be children and ani- mals. Some side-effects noted were adverse skin reactions such as contact dermatitis and hyperkeratosis. Testing done on rats and mice showed a decrease in sperm count and the stopping of fetal and embryonic development.

The following information relating to the basic principles of toxicity testing is given by Mr. Cartwright to provide a better understanding on the use of boric acid for pest control.

Toxicology, The Science of Poisons, By University of California, Berkeley

Toxicity Testing

Before a chemical can be released for sale as a pesticide or drug, extensive toxicity tests must be performed to establish its effectiveness and safety. Indeed, the concept of toxicity testing is now being extended to virtually all manufactured chemicals, not just pesticides and drugs, because of Proposition 65.

A new chemical is tested to establish the type of toxicity and the dose necessary to produce a measurable toxic reaction. Because in the past it has been difficult to compare the results of toxicity tests done in different laboratories, there are now rather strict testing procedures. Toxicity testing has become expensive and extensive, involving many phases. Since different species of animals respond differently to chemicals, a new chemical is generally tested in mice, rats, rabbits, and dogs. The results of toxicity tests in these animals are used to predict the safety of the new chemical to humans.

Toxicity tests are based on two premises. The first premise is that information about toxicity in animals can be used to predict toxicity in humans. Years of experience have shown that toxicity data obtained from a number of animal species can be useful in predicting human toxicity, while predictions based on data obtained from a single animal species may be inaccurate. The second premise is that by exposing animals to large doses of a chemical for short periods of time, we can predict human toxicity due to exposure to small doses for long periods of time.

Acute toxicity studies:

A new chemical first undergoes a series of acute toxicity studies. These tests establish how dangerous it is. The test animals are given various amounts of the chemical in either one oral dose or by a single injection, and are then observed for 14 days. This test often determines the chemical's LD50 dose. The LD50 number is the dosage that will kill 50% of the test animals.

From this test, an estimate is made of the dose of the chemical which will kill 10% of the animals (LD10). The LD10 is then used as the highest dose in a 14 day repeated dose study. At the end of this test, the animals are killed and thoroughly examined (autopsied/necropsied) for any signs of toxic effects (pathology). The purpose of the repeated dose study is to establish the highest dose of the chemical that does not produce any signs of short-term toxicity.

Subchronic toxicity studies:

The next step in toxicity testing is the subchronic toxicity study which is carried out for a period of 90 to 150 days. The highest dose tested during the subchronic study is the dose that was found to produce no signs of toxicity in the earlier 14 day study. Lower doses are also tested.

During this study, the animals are observed closely to see if they develop any signs of toxicity. At the end of the study period, they are autopsied (necropsy), and based on the findings, a maximum tolerated dose (MTD) is selected. The MTD is the highest dose of the chemical that does not alter the animals' life span and it should not have any severely detri- mental effects on the animals' health. The MTD must be established before testing for carcinogenesis.

Chronic toxicity studies on carcinogenesis (oncogenesis):

Carcinogenesis and oncogenesis both mean the production of tumors. The terms tumor, cancer, and neoplasm are all used to mean an uncontrolled progressive growth of cells. In medical terminology, a cancer is considered a malignant (potentially lethal) neoplasm. There are many different types of neoplasm with many different names. Carcinogenic or oncogenic substances are substances which can cause the production of tumors.

Carcinogenesis testing is probably the most expensive part of toxicity testing because these animal studies generally take from 18 months to two years to complete. During carcinogenesis testing, the highest dose of the chemical given is the MTD. It is administered to the animals each day using the same route of exposure that would occur in humans. A close watch is kept on the animals throughout the entire study.

The treated animals are compared to animals who have not been exposed to the test chemical (controls). As animals become older, they start to develop tumors spontaneously (all by themselves). Thus, it is necessary to compare the treated animals with untreated animals to find out whether the effects observed are due to the chemical.

Complete autopsies (necropsies) are done on all the animals, either as they die or at the end of the study. The organs are examined microscopically for tumors or signs of pretumorous change. The government sets strict guidelines for the collection of data and its subsequent evaluation.

Four criteria are used and accepted as evidence of oncogenicity: 1) tumors occurring more often in treated animals than in untreated ones; 2) tumors occurring sooner in treated animals than in untreated ones; 3) treated animals developing different types of tumors than untreated ones; and, 4) tumors occurring in greater numbers of individual treated animals than in individual untreated ones. If the chemical being tested gives rise to any one of the four criteria, it is considered to be oncogenic.

Chronic toxicity studies on teratogenesis:

Teratogenesis is the production of birth defects. A teratogen is anything that is capable of producing changes in the structure or function of the offspring when the embryo or fetus is exposed before birth. Teratogens affect the normal development of the embryo or fetus but not the reproductive genetic characteristics of the offspring. Thus, teratogenic effects are limited to the offspring and are not passed on to future generations.

Teratogenesis studies of new chemicals are generally carried out in three phases in mice, rabbits, and rats. In the first test, male rats are exposed to the chemical for 60 days and female rats are exposed for 14 days. The animals are then mated and the females are treated with the chemical throughout pregnancy and until the offspring are weaned. This phase tests for nonspecific reproductive toxicity.

In the second test, two species of pregnant animals are given the chemical during the most sensitive stage of pregnancy, when the organs of the embryo are starting to develop. At the end of this test, the fetuses are delivered by cesarean section and examined for abnormalities.

The third test for teratogenicity is done on pregnant animals exposed to the chemical during the last third of the pregnancy period and through weaning. This is a less sensitive time for the fetus, but the test is useful for discovering toxicity associated with delivery and early growth. Control animals which are not exposed to the chemical are compared with those treated with the chemical to detect teratogenicity.

Teratogens have a threshold dose level below which teratogenic effects are not pro- duced. There is no direct relationship between teratogenesis and either oncogenesis or mutagenesis.

Chronic toxicity studies on mutagenesis:

Mutagenesis is the production of changes in genetic structure (mutations). Many oncogens are mutagenic and many mutagens are oncogenic. Mutagenic effects are not limited to the offspring and are passed on to future generations. In order for mutagenic effects to be passed on, they must occur in reproductive cells. Thus, mutagenesis is a type of reproductive toxicant.

Mutagenicity testing determines whether or not a chemical might cause genetic alter- ations in humans. This cannot be done directly, but relies on many tests done with bacteria, cell cultures, and animals.

Reproductive toxicity:

The effects of chemical on reproduction are tested by exposing male and female rats to the chemical. The rats are then mated and the number of offspring recorded. If the test chemical has a harmful effect on fertility, it will decrease the number of offspring produced. Other tests can then be done to find out if the chemical is affecting males, females or both.

Special studies:

Occasionally observations made during standard acute and chronic toxicity testing indicate that special studies are needed to examine unusual types of toxicity. For example, if the test animals appear to be behaving strangely, behavioral studies may be done to examine the problem. A chemical may produce only slight depression and drowsiness without other evi- dence of toxicity. However, these effects can be extremely hazardous in situations where a person has to work with dangerous equipment, and behavioral toxicity is especially important in industrial toxicology.

Epidemiological studies:

Delayed toxicity may occur many years after exposure to a chemical and is most often only discovered in retrospective epidemiological studies (studies of the incidence and distribution of toxic effects). Epidemiological studies are crucial to the detection of further occurrences of delayed toxicity.

In Summary:

Obviously we cannot remove all chemicals from our environment. Equally obviously, we cannot afford to spread them around indiscriminately. The focus of toxicity testing is the prevention of harmful effects. Since we cannot think of or test for every type of toxicity that could possibly develop, there have been surprises, some of major importance. However, toxicity testing today is more extensive and more rigorous than ever before. Thus, its level of reliability in predicting toxic effects in humans is also better than ever before. These tests are continually being improved, and continued improvement of the testing procedures will lead to an even greater reliability.

Familiarity with the basic principles of toxicology makes it easier to understand that chemical poisons can be used safely, and that is the first step toward the middle ground of rational use with minimal risk.

(Michael R. Cartwright, Sr. is a third generation licensed professional in the fields of structural pest control and building construction and is also licensed in agriculture pest control. His qualifications are too extensive to print but are available on request from The Reporter. If you or anyone you know has had animals come up with any type of problem after using a boric acid based product in the broadcast application method, Mr. Cartwright would be interested in knowing the details. Send your information in care of The Reporter (Lake Elsinore address).