Mosquito season is approaching in the Northeast, and we had a very wet spring. Which means there are going to be 1) a whole bunch of mosquitoes, and 2) a whole bunch of people arguing about whether to spray them or not. This article aims to examine the toxicology of Sumithrin – the active ingredient in the commonly used insecticide Anvil – and come up with a realistic picture of whether Sumithrin is a deadly poison, a non-toxic chemical, or something in between.
Sumithrin, aka d-phenothrin, is a commonly used insecticide which belongs to the pyrethroid family of chemicals – synthetic analogs of the chemicals that are found in chrysanthemum flowers that the plant makes for self-protection against insects [1]. Sumithrin is a general-purpose insecticide used to kill or control fleas, scabies, and head lice. It also kills ticks—a benefit I’ll discuss later.
Measures of acute toxicity (LD50)
There are a number of standard methods used to determine the risk of chemicals. Some of the most widely used are discussed below. None is perfect, but taken together they give a pretty good idea of how harmful a substance is.
One way to gauge the toxicity of a chemical is to determine the amount of it required to kill 50% of a group of lab animals (usually rats and mice) with a single dose. This measurement is called the LD50, which is short for Lethal Dose 50%. The LD50 is expressed in milligrams per kilogram (mpk) of body weight of the animal. For example, if Chemical X has an LD50 of 10 milligrams per kilogram, then the dose of X required to kill half the rats would be 5 milligrams (an average rat weighs 0.5 kilograms). If Chemical Y has an LD50 of 2,000 mpk this means that it would take 100 mg of Y - about 20% of the body weight of the animal - to kill half the rats. This is an enormous dose for a rat or any other mammal.
Figure 1. LD50 values of sumithrin and other representative chemicals and drugs. Strychnine (top) is the most toxic chemical in the group. Toxicity decreases from top to bottom.
* The value for aspirin is the average of two peer-reviewed studies.
** The LD50 values of sumithrin and aspartame (NutraSweet) are not 10,000 mpk; they are higher than that. No lethal oral single dose in rats could be identified for either chemical, so the value is usually written as >10,000. When something has an LD50 of >10,000, the only way it will kill you is if you get run over by a truck carrying it.
Therefore, a high LD50 in rodents means that the chemical in question has low toxicity, at least in rats or mice. Conversely, a low LD50 indicates that the chemical has significant toxicity. Although LD50 values in rodents cannot be directly converted to a lethal dose in humans, they can serve as a rough approximation of human toxicity, especially when these values are consistent across a number of different animal species. So, it would be incorrect to say that the lethal dose of Chemical X, which is 5 mg in rats, would be 700 mg in humans (average weight 70 kilograms). But it would be fairly safe to conclude that Chemical X will be more toxic to people than Chemical Y, probably by a lot.
The scientific literature contains an enormous amount of data on the toxicity chemicals. One especially useful source is the Hazardous Substances Data Bank, an NIH website now available via PubChem that contains toxicity and carcinogenicity data, etc. on 400,000 chemical compounds. All of the toxicity data contained in this article is derived from this database.
Limitations of Figure 1
Of the nine chemicals and drugs listed in Figure 1, acetaminophen, aspartame, and sumithrin are the least toxic in rats, while strychnine, cyanide, and nicotine are the most. Calculating a lethal human dose, as I mentioned before, cannot be done by using the LD50 value and adjusting the dose from rats to humans based on body weight. But just to illustrate the lack of acute toxicity of sumithrin, I did the "math" anyhow. If rat LD50 values were the same as those of humans, then the toxic dose of sumithrin in people would be 182 grams - 36 teaspoons. You are unlikely to eat 36 teaspoons of sumithrin in any real-world setting.
Cumulative exposure
Most people have a misguided impression about the everyday chemicals that we are exposed to. A common belief is that we live in a cocktail of toxic substances and that these build up in our bodies, possibly giving rise to soaring cancer rates. There are two misconceptions here:
1. There is no surge in cancer rates. They have remained steady or have slightly declined over the past 24 years.
Age-adjusted incidence (top) and mortality (bottom) of all cancers (per 100,000 people) between 1992-2016. Source: Cancer Stat Facts: Cancer of Any Site.
2. With few exceptions, chemicals do not accumulate in our bodies. This is because our livers – the primary site of metabolism of drugs and chemicals, natural or synthetic – break down the chemicals or drugs that pass through them, converting these substances into water-soluble metabolites that are usually excreted in the urine.
Sumithrin, like most chemicals, does not bioaccumulate. In rats, the half-life in blood is about one hour (rapid metabolism), meaning that after one hour, half of it is gone, and after 8 hours (four half-lives), almost all of the chemical is gone. Even after administration of a single large (200 mg dose, 2% of the weight of the rat), more than 95% of the chemical was metabolized and eliminated after 48 hours.
Also, keep in mind that these numbers represent the fate of sumithrin when taken orally. Sumithrin is not efficient in penetrating the skin, so skin exposure will give lower blood levels to begin with.
Inhalation
Even though the chemical has very low toxicity when inhaled by rats, when it is inhaled in significant quantities by humans, sumithrin can cause "nausea, vomiting, throat irritation, headache, dizziness, and skin and eye irritation," but the hysteria surrounding spraying is unwarranted. According to data from the Poison Control Center between 1992 and 2005, there was an average of 180 exposures per year, with only 25% of these (45) resulting in symptoms [2]. So, it is not surprising that a 2011 paper, "Bystander Exposure to Ultra-Low-Volume Insecticide Applications Used for Adult Mosquito Management," concluded:
"Our results support the findings of previous risk assessments that acute exposures and risks to humans from [Ultra-Low-Volume] insecticides are well below regulatory levels of concern."
C. Preftakes, et.al, International Journal of Environmental Research and Public Health. 2011 Jun; 8(6): 2142–2152.
A little does not equal a lot
Although this statement seems self-evident, it is mind-boggling how often people get it wrong by failing to differentiate between the biological effects of trace quantities and a bottle full of the same chemical, even though in the 16th century the Swiss physician Philippus Aureolus Theophrastus Bombastus von Hohenheim, aka, Paracelsus, coined the phrase "All things are poison, and nothing is without poison, the dosage alone makes it so a thing is not a poison," which has been shortened to "the dose makes the poison"
Paracelsus, the "father of toxicology." Image: Wikipedia
This simple adage is the main reason that sumithrin can be sprayed to kill mosquitoes while sparing humans. Common mosquitoes weigh 2.5 mg. An average human weighs 70 kilograms, which is 28 million times more than a mosquito. This is why such insecticides can be toxic to bugs but not to people, but it is not the only reason. It is also known that mosquitoes metabolize sumithrin more slowly than humans, so it builds up in the bugs but not in people [3,4].
Carcinogenicity
There are numerous ways to evaluate whether a chemical will be carcinogenic in humans. Here are two of the most important:
1) Genotoxicity (DNA damage). Chemicals that damage DNA always raise a red flag because gene damage can be a precursor to cancer. Many experimental drugs have met with an untimely demise because of a positive Ames test [5]. Although not all chemicals that are genotoxic are carcinogens, most carcinogens are genotoxic. There are a number of other lab tests that are used to determine the possible carcinogenicity of chemicals.
2) High dose rodent studies. Rat models of cancer are notoriously awful. Part of the reason is that rats are not little humans, but the primary reason is the way the tests are conducted. Typically, rats are fed a very high dose – much higher than a human will ever be exposed to – for their entire lives (two years) and then examined for tumors. Although this model is clearly unrealistic, the high dose feeding is only part of the problem. The choice of rats is the other. The Sprague-Dawley rat is frequently used for this experiment; this rat is bred to easily develop tumors, so much so that the control animals (not given the chemical being tested) develop so many tumors that it can be difficult to determine whether a chemical caused the tumor or the rat developed it on its own.
Sumithrin is neither genotoxic nor carcinogenic. There is no agency, US or international, that lists the chemical as a possible carcinogen. Even California's ridiculous Proposition 65, which requires cancer warning labels on hundreds of chemicals (also on hotel rooms, in cars, handbags...and much more) does not contain sumithrin. But the list does contain alcohol – a known human carcinogen. It would be unusual to see people hiding in their homes with the windows closed and air conditioners running when people walk by drinking beer.
5. Concern for pets and the environment
No poison is perfect. Although sumithrin is safe for humans, rats, and mice, the same cannot be said for our pets, especially cats, since they cannot metabolize the chemical. Sumithrin is still found in some dog flea collars, but it has been withdrawn from products intended for cats due to its high toxicity to them.
Sumithrin is highly toxic to bees, fish, and amphibians. It should not be sprayed in waterways. Most spraying is a low-volume ground application, not a plane indiscriminately dropping it over vast areas.
Persistence in the environment is always a concern when herbicides and pesticides are used. The persistence of sumithrin depends on conditions; it decomposes to non-toxic breakdown products within a few hours in air (especially in sunlight) and less than a day on the surface of plants. But its half-life in soil can vary from 1 to 16 days. Also, it is not water-soluble, so groundwater contamination is unlikely.
To spray or not to spray?
It is easy to conclude that any given chemical or drug should not be used if one examines only the risks of using it without considering the risks of not using it. Both mosquitoes and ticks are vectors for numerous (and emerging) bacterial and viral infections and when they are not controlled, human disease will inevitably result.
West Nile Virus is a well-known, nasty infection transmitted by mosquitoes, but there are other pathogens transmitted by mosquitoes you'd do well to avoid. Dengue virus, endemic to tropical regions, has now been found in Texas, Florida, and Hawaii. Eastern Equine Encephalitis (EEE) is perhaps the most dangerous of all mosquito-transmitted diseases. It is spread to horses and humans by mosquitoes. Although still rare, the fatality rate for infected humans can be as high as 30-75% in symptomatic cases. Additionally, ticks, which are also killed by sumithrin, spread a number of very scary viral infections, such as Lyme Disease, Rocky Mountain Spotted Fever, Colorado Tick Fever, and Powassan Encephalitis.
Making sensible decisions
Public health decisions require sound science, not reflexive reactions based on misinformation, ignorance, or personal beliefs. The judicious use of insecticides such as sumithrin reflects a trade-off: minimal, manageable risk in exchange for protection against much greater threats. That’s not chemical hype—it’s sound public health.
Whether the issue is vaccination or pest control, feel-good, easy-sounding memes may be attractive alternatives to actual facts, but in the absence of sound science, the easy answer is usually the wrong answer.
NOTES:
(1) Insecticide marketers engage in a sleight-of-hand by saying pyrethroid insecticides are in the same chemical family as the natural pesticides from chrysanthemums. This is technically true, but meaningless. It implies that the insecticides are somehow safer because they are "related" to chrysanthemums. That is nonsense. Each pyrethroid has its own toxicity profile. Sumithrin is safe because it is non-toxic, not because it is structurally similar to the natural insecticides.
(2) Reference: d-Phenothrin (Sumithrin®): Occupational and Residential Exposure Assessment for the Reregistration Eligibility Decision (RED); U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, U.S. Government Printing Office: Washington, DC, 2007; pp 1-23.
(3) Another "active" ingredient found in Anvil insecticide is piperonyl butoxide. Piperonyl butoxide is not an insecticide; it inhibits the enzyme that clears sumithrin from the mosquito, making it more effective. Piperonyl butoxide is neither toxic nor carcinogenic. There is one case report of a fatal overdose, but the victim drank between one pint and one quart of the chemical. Bad move.
(4) Piperonyl butoxide, which is typically found combined with sumithrin, is a synergist that inhibits metabolic enzymes in insects to boost the effectiveness of pyrethroids. It is not classified as toxic or carcinogenic at standard exposures
(5) The Ames test, a widely used and important method for determining carcinogenicity, uses bacteria to test for the ability of chemicals to mutate genes. It was invented by biochemist Dr. Bruce Ames in the 1970s. Ames was one of the founders of ACSH.
Josh Bloom
Director of Chemical and Pharmaceutical Science
Dr. Josh Bloom, the Director of Chemical and Pharmaceutical Science, comes from the world of drug discovery, where he did research for more than 20 years. He holds a Ph.D. in chemistry.
