Bellinger calculates a total loss of Last month, more research brought concerns about chemical exposure and brain health to a heightened pitch. The experts named 12 chemicals—substances found in both the environment and everyday items like furniture and clothing—that they believed to be causing not just lower IQs but ADHD and autism spectrum disorder.
Pesticides were among the toxins they identified. Landrigan had issued that same warning, unprompted, when I spoke to him the week before. For decades, chlorpyrifos, marketed by Dow Chemical beginning in , was the most widely used insect killer in American homes.
It paid the fine and, in , withdrew chlorpyrifos from household products. Landrigan has the credentials of some superhero vigilante Doctor America: a Harvard-educated pediatrician, a decorated retired captain of the U. Naval Reserve, and a leading physician-advocate for children's health as it relates to the environment. Chlorpyrifos is just one of 12 toxic chemicals Landrigan and Grandjean say are having grim effects on fetal brain development. Their new study is similar to a review the two researchers published in , in the same journal, identifying six developmental neurotoxins.
Only now they describe twice the danger: The number of chemicals that they deemed to be developmental neurotoxins had doubled over the past seven years.
Six had become Their sense of urgency now approached panic. The chemicals they called out as developmental neurotoxins in were methylmercury, polychlorinated biphenyls, ethanol, lead, arsenic, and toluene.
Grandjean and Landrigan note in their research that rates of diagnosis of autism spectrum disorder and ADHD are increasing, and that neurobehavioral development disorders currently affect 10 to 15 percent of births.
In perhaps their most salient paragraph, the researchers say that genetic factors account for no more than 30 to 40 percent of all cases of brain development disorders:.
Silent pandemic. When public health experts use that phrase—a relative and subjective one, to be deployed with discretion—they mean for it to echo.
When their paper went to press in the journal The Lancet Neurology , the media responded with understandable alarm:. When I first saw these headlines, I was skeptical. With each of these substances, the question is just how much exposure does it take to cause real damage. They kill insects by the same mechanism that sarin gas kills people, causing nerves to fire uncontrollably.
But like asbestos, they are still legally used in U. I found that the real issue was not this particular group of 12 chemicals. Most of them are already being heavily restricted. This dozen is meant to illuminate something bigger: a broken system that allows industrial chemicals to be used without any significant testing for safety. Federal health officials, prominent academics, and even many leaders in the chemical industry agree that the U.
Yet parties on various sides cannot agree on the specifics of how to change the system, and two bills to modernize testing requirements are languishing in Congress. In order to process even basic information, billions of chemical signals are constantly being carried between neurons. The undertaking is so onerous that even though your brain is not moving like, say, the powerful muscles in your legs , it uses around 10 times more calories per pound than the rest of you.
Most of that industrious brain and its 86 billion neurons were created in a matter of months. During the first few weeks of gestation, when your mother knew you only as morning sickness and you were a layer of cells huddled in one corner of her uterus, those cells lined up, formed a groove, and then closed to form a tube.
One end of that tube eventually became your tiny spinal cord. The rest expanded to form the beginnings of your brain. For a brain to develop properly, neurons must move to precise places in a precise sequence.
They do so under the direction of hormones and chemical neurotransmitters like acetylcholine. The process is an intricate, fast-paced dance on a very tiny scale. Each nerve cell is about one hundredth of a millimeter wide, so it has to travel its own width 25, times just to move an inch—which some neurons in the cortex must. At any point, that cell can be knocked off course.
Some of the neurotoxins Grandjean and Landrigan discuss have the potential to disrupt this journey, in a slight or serious fashion. By the third trimester, the surface of the brain begins folding itself into wrinkled peaks and valleys, the gyri and sulci that make a brain look like a brain. Specific areas of that cortex learn to process specific aspects of sensation, movement, and thought, and that starts in the uterus. The nature-nurture duality begins at conception.
By age two, almost all of the billions of brain cells that you will ever have are in their places. Except in the hippocampus and one or two other tiny regions, the brain does not grow new brain cells throughout your life. When brain cells die, they are gone. So its initial months of formation, when the brain is most vulnerable, are critical. Federal health officials are aware of this risk. There are a few products containing permethrin that are licensed for use in cats mostly flea collars and flea powders.
Figure 4. Permethrin toxicosis may occur after accidental use of a canine spot-on product on a cat. The toxic effects of permethrin are caused by alteration of the kinetics of voltage-dependent sodium channels in nerve membranes, which causes repetitive discharges or membrane depolarisation.
Some pyrethroids may also inhibit GABA receptors. This inhibits the GABAa-receptormediated chloride ion influx, the physiological function of which is to induce presynaptic inhibition.
Loss of this inhibition can lead to hyperexcitability of nervous tissue; this may be the mechanism by which these compounds produce convulsions. In mammals, permethrin is rapidly biotransformed and detoxified by ester hydrolysis or oxidation. As a result, it is of relatively low toxicity in most mammals. Dermal exposure is the most common route in cats but although there is probably some dermal absorption some permethrin may be ingested via grooming.
The feline liver is relatively inefficient at glucuronide conjugation leading to slow excretion and accumulation of permethrin metabolites and may be the reason for the common occurrence of toxicity in cats.
Signs of permethrin toxicosis usually start within 1—3 hours but are sometimes delayed up to 36 hours. The duration of effects is generally 1—3 days, but can be longer, although these data were derived from cases before the use of lipid emulsion. Common signs of permethrin poisoning include vomiting, diarrhoea, hypersalivation, thirst, ataxia, incoordination, dilated pupils, tachycardia, hyperexcitability, hyperaesthesia, hyperthermia, tachypnoea, tremor, twitching, muscle weakness and fasciculations, convulsions and respiratory distress as a result of weakness of respiratory muscles.
Rarer effects include hallucinations, temporary blindness, hypothermia possibly caused by poor drying after washing , cardiac arrhythmias and cardiac arrest. Prolonged seizure activity could result in cerebral oedema, irreversible brain damage and myoglobinuria-induced nephropathy Richardson, Dermal exposure to permethrin products may also cause local irritation and alopecia, possibly caused by the solvent vehicle.
After ingestion, permethrin is rapidly absorbed and so emetics and activated charcoal are unlikely to be of use. Dermal exposure is common in cats and in these cases they should be washed with copious amounts of lukewarm water and detergent permethrin is not water-soluble. The use of hot water should be avoided as this increases dermal perfusion and may result in increased dermal absorption.
Cats with long hair may need to have exposed areas clipped. Care should be taken to dry the animal well. A decrease in body temperature may exacerbate effects, because there is an inverse relationship between sodium influx and temperature Whittem, Following decontamination the cat should be collared to prevent grooming and should be isolated from other animals to prevent cross-contamination.
Thereafter, treatment is essentially symptomatic and supportive, with the aim of controlling CNS effects. Care should be taken to maintain hydration and body temperature. Pyrexia as a result of increased muscular activity may cause cerebral oedema leading to continued convulsions.
Cooling measures should be used carefully, as a low body temperature may lead to increased toxicity. Diazepam may be of use to control increased muscular activity twitching, fasciculation or convulsions , but it is often ineffective in severe cases. Methocarbamol is commonly used Volmer et al, ; Richardson, ; Hansen, If injectable methocarbamol is unavailable, oral tablets can be crushed, mixed with saline and given rectally Table 1. A randomised, controlled clinical trial in cats with permethrin toxicity compared cats treated with and without lipid infusion.
The study used a specially designed and validated system describing six clinical stages of poisoning. The study found that cats treated with lipid infusion improved earlier than cats that did not receive lipid Peacock et al, Early use of lipid infusion is recommended if the exposure is thought to be significant, the cat has significant neurological signs, or it is failing to respond to other therapies.
Rapid improvement can occur in cats with permethrin poisoning given intravenous lipids Haworth and Smart, ; Muentener et al, Ivermectin is an avermectin antiparasitic agent and dogs and less commonly cats may be exposed via ingestion of ivermectin directly often spilled or dropped by treated horses, for example ; from ingestion of the faeces of treated animals; or by parenteral exposure. Avermectins are thought to act in mammals by potentiating the release and binding of GABA-gated chloride channels in the CNS Snowden et al, , causing diffuse cerebellar and cerebral cortex dysfunction.
In mammals avermectins do not readily cross the blood—brain barrier, but some breeds such as collies and related breeds are particularly susceptible to ivermectin toxicosis. This codes for P-glycoprotein, which is present in the membrane of the blood—brain barrier and limits penetration of substances into the brain. Changes in expression of P-glycoprotein allow increased uptake of ivermectin into the brain Edwards, Susceptibility is only found in dogs that are homozygous for the mutation Mealey et al, The cause of blindness in ivermectin toxicity is not known, but both intracranial and retinal processes appear to be involved Kenny et al, All breeds develop the same clinical signs, but susceptible breeds show signs at lower doses than non-susceptible breeds.
Onset of ivermectin toxicosis may occur within 12 hours of oral exposure with signs progressing over the following 12—24 hours. Time to recovery varies with the severity of poisoning; in mild cases it may occur within 24 hours and in severe cases complete recovery may take 1—2 weeks, or sometimes longer. Coma can last several days Paul et al, ; Hopper et al, The earliest signs of ivermectin toxicosis are usually ataxia, depression, hypersalivation and dilated pupils.
There may be vomiting; confusion and disorientation; and sluggish or absent pupil reflexes. Severe intoxication is characterised by blindness, tremors, convulsions, hyperaesthesia, hyperreflexia, hypo- or hyperthermia, weakness, coma and paralysis.
Bradycardia and respiratory depression can also occur. Sudden-onset blindness can occur in the absence of severe clinical signs usually with only dilated pupils and mild drowsiness in non-susceptible dogs i.
Ivermectin-induced blindness can last days or weeks, with complete resolution of effects Kenny et al, Depending on the condition of the animal, the amount ingested and the time since ingestion, it may be appropriate to induce vomiting. Repeated dose activated charcoal may be helpful to enhance elimination and prevent reabsorption, as ivermectin is excreted in the faeces. Management thereafter is supportive, with monitoring of body temperature, hydration status and respiratory function.
Oxygen may be required in animals with respiratory depression and nutritional support in those with prolonged coma. Atropine has been used in the management of bradycardia Heit et al, Lipid emulsion in recommended, and has been used in numerous cases in companion animals with ivermectin toxicosis e. Clarke et al, ; Bates et al, ; Epstein and Hollingsworth, ; Kidwell et al, ; Jourdan et al, ; Becker et al, , particularly as benzodiazepines and barbiturates should be avoided as they enhance GABA-mediated inhibitory transmission at GABAa receptors and avermectin drugs enhance the effect of GABA Snowden et al, which can prolong recovery.
Anaesthetic agents that do not act primarily on GABA receptors should be used instead, such as propofol Snowden et al, The mechanisms of many of the substances causing neurological effects is unknown. Few have a specific antidote, therefore management in most cases is supportive, with the focus on controlling or preventing seizure activity. Intravenous lipid emulsion can be used in the management of poisoning with a number of common substances causing neurological effects, such as cannabis, tremorgenic mycotoxins, permethrin and ivermectin.
Sign up to The Veterinary Nurse's regular newsletters and keep up-to-date with the very latest clinical research and CPD we publish each month. Review Poisons affecting the neurological system. Box 1. Other potential toxicological causes of neurological effects in companion animals Any substance causing central nervous system CNS depression, e. Mechanisms of toxicity The mechanism of metaldehyde toxicosis in mammals is not clearly understood. Clinical effects Onset of signs of metaldehyde toxicosis may be very rapid, often within 30 minutes of ingestion, but may be delayed for up to 3 hours.
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