Neonicotinoids (neonics) are the most widely used class of insecticides in the US and worldwide. They are known to be a major contributor to pollinator declines, and recent scientific evidence shows impacts on human and wildlife health as well.
In a recent CHE webinar, Dr. Jennifer Sass provided an overview of scientific evidence on the neurodevelopmental and reproductive health effects of neonicotinoids. Dr. Jodi Flaws discussed her research on the effects of one neonicotinoid – imidacloprid – on the health of the male and female reproductive system in laboratory animals. She also discussed her recent review of existing literature on reproductive effects of neonicotinoid pesticides, including both male and female impacts.
Systemic pesticides
Many neonics are used as seed coatings, particularly for conventional corn and soy production. The seeds are pre-treated before they are planted. When plants are grown from these seeds, the neonics get distributed throughout the plants. As a result, there is no way to wash them off of produce. Humans are exposed by eating contaminated food, as well as through drinking contaminated water and through contact with pets that are exposed through commercial flea and tick collars.
Epidemiological studies have shown various health effects in people who have been exposed to neonics, including memory loss, finger tremors, and altered metabolism. Neonics pass easily from a pregnant mother to the fetus, which can expose the fetus during vulnerable development times, causing health impacts later in life — including harm to reproductive systems. Infants can also be exposed through breast milk.
Neonics are structurally similar to nicotine. Much of the research that Flaws shared focuses on the neonic imidacloprid (IMI). Compared to the other neonics, IMI has the highest detection frequency on produce and is also present in drinking water throughout the US and in other countries.
Neurotoxicants
Neonics are neurotoxicants by design. Neonics bind to nicotinic acetylcholine neuroreceptors, blocking neurotransmitters from reaching the postsynaptic neurons they would normally bind to. This binding to neuron receptors is what makes neonics neurotoxic to insects, with exposure causing overstimulation of the nervous system and eventually causing paralysis and death.
It was previously thought that neonics would not be harmful to mammals, despite being highly neurotoxic to insects. Research in recent years, however, has called this into question.
It was once thought that mammals did not have the targeted receptors. We now know that mammals do have these receptors. It was also thought that certain neonics, such as IMI, had a much higher binding affinity for these receptors in insects than in mammals. We have since learned that IMI can be transformed by liver enzymes into metabolites that have a higher affinity for the mammalian receptors than IMI.
Reproductive toxicants
Flaws described research into whether or not IMI and other neonics might be reproductive toxicants in mammals. She explained that neonics can reach reproductive tissues, including ovarian follicles (which contain unfertilized eggs). Follicles also play an important role in producing reproductive hormones. Research shows that the ovary itself has receptors that can bind IMI and other neonics.
Flaws’ research found evidence that ovarian follicles also metabolize IMI. The same enzymes that metabolize IMI in the liver are also found in the ovary. The enzymes in the ovary convert IMI to intermediate metabolites before eventually converting it to 6-chloronicotonic acid (6CNA). This process could be producing compounds in the ovaries that are more toxic than IMI.
Flaws’ research then looked into whether IMI and its metabolites are toxic to the ovary. An intermediate metabolite that they focused on was desnitro-imidacloprid (DNI). To assess toxicity, the researchers looked at any impacts on follicle growth or hormone levels in vitro. Exposure to DNI was found to inhibit follicle growth and increase the rupture of the follicles. The research also found impacts on hormone levels. IMI increased secretion of progesterone, while DNI decreased secretion of progesterone, testosterone, and estradiol.
In addition, the researchers found in vivo evidence with mice that IMI reduces follicle numbers, which would lead to decreased fertility. More long-term research is needed here to measure impacts over time.
Studies have found that other neonics can also affect both male and female reproductive systems. Several studies have shown that acetamiprid reduces fertility in rodents and leads to precocious puberty. Rodent studies have shown that exposure to clothianidin increases the number of stillborn pups. In female rodents, thiacloprid has been shown to cause uterine tumors and ovarian luteomas. Studies have also shown associations between each of these neonics and negative impacts on male fertility.
Human studies have found widespread exposure to mixtures of these neonics. Epidemiologic studies are showing associations of these mixtures with problems during pregnancy that could lead to fetal growth restriction and problems in the offspring.
"There are also studies showing that exposure either during pregnancy or during adolescence has been associated with precocious puberty in both boys and girls."
Two recently released factsheets highlight these and numerous other health risks from neonicotinoids, one from U.S. Right to Know and one from Natural Resources Defense Council.
Unsafe products & unnecessary uses
Research continues to show that neonics are not as safe for mammals as originally thought. They are also highly toxic to invertebrates, including beneficial ones such as bees, butterflies, and aquatic organisms.
A 2024 review of acute human neonic poisoning incidents concluded:
“Given the evidence of neurotoxicity, EPA should use its legal authority to cancel unsafe products and unnecessary uses – including from seed treatments, and residential pet and lawn care products – to prevent further human suffering.”
For more, see our webinar: New Science on Neonicotinoids: Reproductive & neurodevelopmental health effects.
This organizational blog was produced by CHE's Science Writer, Matt Lilley.