The disinfectant commonly used in this epidemic situation may affect fertility and fetal development?

Quaternary ammonium compounds are widely used in public places in medical, catering and other industries, and the epidemic situation has increased the frequency and time of our exposure. However, some scientists have found that some laboratory animals living in the environment disinfected with quaternary ammonium salt have shown a worrying decline in fertility, and some of their offspring also have neural development defects. Although no direct link has been found between this commonly used disinfectant and human health, some scholars believe that it is time to be vigilant against the once considered “safe and harmless” compound. < / P > < p > at first glance, this 10 day old mouse embryo looks no different from other embryos. However, from the microscopic observation, Terry hrubec found something wrong. There are tiny gaps in the neural tubes of the embryo, which develop into the brain and spinal cord of mice. It’s not completely closed. This happened in January 2009. As a reproductive and developmental toxicologist at Virginia Tech University and Edward via College of orthopedic medicine, hrubec is studying how to prevent this neural tube defect. She exposed a group of pregnant mice to drugs that cause the defects, hoping to see them in their embryos. But the defective embryo came from her control group, healthy mice that were not exposed to the drug. Finally, hrubec found neural tube defects in 10% of the control embryos. < / P > < p > hrubec repeated the experiment to ensure that she did not confuse the pregnant mice or embryos in the experimental group, but the results remained the same. She was so confused that she had to go to the animal keeper in the laboratory. < / P > < p > the answer is still disappointing, the source of these mice has not been changed, their diet has not been changed, and their food and shelter have not been contaminated by pathogens. The results are true: a new disinfectant was used in the animal room. To prevent laboratory animals from getting sick, animal carers usually clean the floors, walls and shelves every week and wipe the floors every day – they always use chlorine based disinfectants. But at some point in the autumn of 2008, staff switched to a mixture containing alkyl dimethylbenzyl ammonium chloride (adbac) and Didecyl dimethyl ammonium chloride (ddac). These compounds are known as quaternary ammonium compounds or quaternary ammonium salts, which are common in all kinds of consumer goods. < p > < p > through further research, hrubec found the relationship between adbac and ddac and development / fertility problems in mice. At the same time, other scientists have also found that quaternary ammonium salt has a negative impact on the process of cell life. Now, covid-19 is sweeping the world. In order to fight the epidemic, hospital staff, school guards, public transport operators and owners have begun to disinfect buildings. According to the recommendation of US Environmental Protection Agency, half of the disinfectants that can effectively fight against new coronavirus are quaternary ammonium salts. Libin Xu, a biochemist at the University of Washington in the United States, is very concerned about this. He added that the public may know that quaternary ammonium salts can kill bacteria, but Xu’s study found that quaternary ammonium salts also disrupt key cellular pathways. < / P > < p > up to now, researchers have not reported that quaternary ammonium salts have systemic toxicity to human body. However, at least one regulator would like to know more about these compounds. The California Department of Public Health issued the covid-19 guidelines for schools on July 17, which clearly stipulates that disinfection products containing chemicals that cause asthma, including quaternary ammonium salts, should be avoided. “We recommend, as far as possible, the use of disinfectants that do not contain quaternary ammonium salts or other harmful chemicals,” the Ministry of Health said in a statement to C & en < / P > < p > quaternary ammonium compounds are composed of hundreds of compounds, which contain at least one positively charged nitrogen atom, usually linked to four alkyl or benzyl groups. In 1935, German pathologist Gerhard Domagk, a Nobel laureate, discovered their fungicidal properties. Domagk found that if only one of the groups carried by cationic nitrogen was a long-chain alkyl group, the compound could kill microorganisms. The positive charge of the molecule helps it attach to the negatively charged surfaces of bacteria and viruses. For bacteria, the long alkyl chain will be inserted into the lipid membrane on the surface, which will break the thin envelope and make the internal substances leak out. In the case of viruses, quaternary ammonium salts can destroy the protein and lipid structures that envelop their genetic material. Shortly after the discovery of this property of quaternary ammonium salts, doctors realized that adbac with 12 carbon alkyl chains could sterilize hands and instruments before surgery, and the compound entered the market under the name of zephirol (also known as benzalkonium chloride). By 1940, restaurants and dairy farms also used quaternary ammonium salt in disinfection of related equipment. < / P > < p > moreover, the role of these compounds is more than disinfection. The bactericidal properties of adbac make it an effective preservative in wood treatment and eye drops. Another quaternary ammonium salt, 1-16 alkyl pyridinium chloride (CPC), is used as an effective ingredient in slobber, nasal spray and throat lozenges. Some quaternary ammonium salts are also used as pesticides, such as paraquat and diquat. Other quaternary ammonium salts have become surfactants in detergents and shampoos, and also shine in oil and gas production. They are also found in drying paper and Fabric Softeners – they carry a positive charge that helps prevent the accumulation of static electricity on clothing. According to two public databases on consumer goods, quaternary ammonium compounds can be found in thousands of household products around the world. According to one estimate, the market value of quaternary ammonium salt will reach 963.7 million US dollars in 2019. Quaternary ammonium compounds entered the market before EPA began to regulate the production and sale of potentially hazardous chemicals under the toxic substances control act of 1976. This allows quaternary ammonium salts to be considered as chemicals already on the market and can be sold without safety assessment. Moreover, these compounds have passed extensive safety tests. Keith Hostetler, an expert at a toxicology consulting service, said EPA is currently working on a new risk assessment plan for quaternary ammonium compounds, which will be released for public consultation in 2021. < / P > < p > after learning that quaternary ammonium salt disinfectant was used in animal facilities at his university, hrubec began to look for data on the toxicity of the compound. Unfortunately, she did not find any studies on the reproductive or developmental toxicity of quaternary ammonium salts, but a Q & a published in nature made her find that she was not the only one who was disturbed by the chemical (nature 2008, DOI: 10.1038 / 453964a). < / P > < p > this article details Patricia Hunt’s experience. In 2005, hunt moved from Case Western Reserve University Medical School, which does not disinfect animal rooms with quaternary ammonium salts, to Washington State University, which uses quaternary ammonium salts. She noted that there was a significant decline in the fertility of mice at Washington State University, which used quaternary ammonium disinfectant for aerosol spray and cleaning after a parasite outbreak, which further reduced the fertility of mice. < / P > < p > after contacting hunt, hrubec examined his own reproductive records and realized that fertility had also declined since the school changed the disinfectant. Although Hunt had stopped studying the toxicity of quaternary ammonium salts at that time, hrubec decided to investigate further to understand the potential risks of these commonly used chemicals. “If quaternary ammonium is toxic to mice, it is likely to cause problems in humans as well,” she said < / P > < p > next, hrubec transferred the mice to a facility that did not use quaternary ammonium salt disinfectant, and the neural tube development defects of offspring animals disappeared. She followed up on these defects and found that even if the mother was not exposed to quaternary ammonium salts and only the father was exposed, the embryo still had neural tube defects (birth defects res.2017, DOI: 10.1002/bdr2.1064). < / P > < p > in the second study on reproductive capacity, hrubec compared sperm quality of male mice living in quaternary ammonium disinfection facilities with those living without quaternary ammonium salt（ Reprod.Toxicol .2016 DOI：10.1016 / j.reprotox.2015.10.006）。 Hrubec said the experiment mimicked people’s daily exposure to quaternary ammonium. She found that sperm counts and motility were reduced by about 25% and 10% in male mice living in a quaternized environment. However, the research of hrubec has been questioned by Hostetler. The latter believed that the dosage of quaternary ammonium salt fed to mice in this study far exceeded the daily exposure dose of human beings, and in subsequent experiments, it used the form of environmental exposure that could not be quantified. He also pointed out that EPA had evaluated the reproductive and developmental safety of adbac and ddac based on six studies in rats and rabbits conducted in 1989-1992. In these studies, no toxicity was found to the fetus or mother of experimental animals. Jamie DeWitt, a toxicologist at East Carolina University, agrees with Hostetler. DeWitt believes that it is necessary to truly assess the harm of specific chemicals to human health, and that the dose range similar to the actual human exposure should be used in the study, and the exposure mode that human may experience should be selected. But that doesn’t mean that hrubec’s research is ineffective: “it’s a good attempt,” she added She pointed out that hrubec’s and Hunt’s experience with quaternary ammonium salts reflects the first discovery of an endocrine disrupting chemical. “I think these papers are very good at starting to identify the hazards associated with quaternary ammonium compounds.” < / P > < p > after hrubec first published a study on the toxicity of quaternary ammonium salts in 2014, two researchers contacted her and started cooperation. They had their own research on quaternary ammonium salts before that. Gino cortipasi, a toxicologist at the University of California, Davis, has been studying diseases involving mitochondria, the energy factory of cells. Mitochondrial dysfunction can lead to excessive fatigue and can cause aging and most chronic diseases. Starting around 2010, cortopassi and his team conducted a large-scale, high-throughput screening campaign to find compounds that could enhance mitochondrial function and serve as new treatments for such diseases. They conducted five cell tests on 1600 compounds in the pharmakon Library of microsource discovery systems to see how these compounds affect various indicators of mitochondrial health, such as oxygen consumption and the synthesis of adenosine triphosphate, a molecule used to store energy. < / P > < p > the researchers found that 11 compounds could slow down these two processes. Six of them are quaternary ammonium salts, including adbac and CPC (environ).