HEALTH EFFECTS OF HEXANE
What studies reveal about hexane and the human body
The harmful health effects of n-hexane have been studied for many years. Numerous studies suggest that adverse neurological, respiratory, developmental, and reproductive effects are among the health issues related to exposure to n-hexane. The following studies will provide more information regarding the toxic effects of n-hexane.
What are Hexane Metabolites and how are they formed?
When Hexane enters a human or animalโs body, the liver tries to eliminate it as it is foreign to the organism. But because n-hexane is not miscible in water, the liver has to turn it into other molecules to allow its elimination in the urine. There are biological reactions called the โmetabolic pathwayโ that occur as the body breaks down the hexane molecule to produce what is called a โMetabolite.โ Various enzymes present in the liver convert the hexane through a series of oxidative steps that leads to the formation of several metabolites including 2,5-hexanedione (2,5-HD). This metabolite has been shown to cause the chronic toxicity of hexane.
How the toxicological studies help to understand the impact of hexane on human health?
The metabolic pathway is often similar between rats and humans. It is the reason why rodents are a model of choice for toxicological studies. For n-hexane however, rats have a capacity to turn n-hexane into a non-toxic metabolite which doesnโt exist for humans. That is the reason why toxicological studies on rats systematically underestimate the toxicity of n-hexane compared to the one found for humans.
Today, to overcome that difficulty, nearly all scientists assess the n-hexane toxicity by exposing rodents directly to 2,5-hexanedione (also named by the generic name gamma-diketone), the human toxic metabolite. Other scientists follow pyrrole adducts, a toxic compound which derives from 2,5-hexanedione for the same purpose.
The following compilation of the toxicological studies related to n-hexane, 2,5-hexanedione, pyrrole and gamma-diketone allows to better understand and evaluate the toxic effects of n-hexane on human health.
Key studies on n-hexane toxicity
Neurological damages
The nervous system is the main target of n-hexane toxicity.
Its neurotoxic potential was first documented in occupationally exposed humans in their workplace in the sixties and then confirmed in experimental animals.
In countries such as France, Italy or Germany, n-hexane has been classified as an occupational neurotoxic since the seventies.
Repeated exposure to n-hexane damages nerves and causes their degeneration. The typical symptoms are numbness and reduced sensitivity in the feet and hands, followed by loss of distal reflexes and weakness of the intrinsic muscles in the legs and arms, leading to peripherical sensory polyneuritis or polyneuropathies. Patients can lose their capacity to walk.
Repeated exposure to n-hexane also damages the optical nerves and causes vision impairment.
The toxicity of 2,5-hexanedione can be exacerbated by a preexisting pathology which reduces the bodyโs capacity to eliminate this toxin. Due to the 2,5-hexanedione ingested with their food, people with type 2 diabetes or uremia develop polyneuropathies like those found in occupationally exposed people.
Recent tests on mice show that even low dosages of 2,5-HD (2,5 or 5 mg/kg body weight/day) significantly damage the brain of overweight or obese animals and cause cognitive impairment when non-exposed obese mice have the same performance than control animals on the Morris Water Maze test (MWM).
The toxicity of the 2,5-hexanedione can be exacerbated by age. People over sixty develop a โcryptogenicโ polyneuropathy, a pathology like the one of occupationally exposed workers without any known occupational exposure. There is a high probability this pathology is due to the accumulation of n-hexane ingested from food and the reduced capacity of the aged body to deal with it.
Parkinson’s disease
N-hexane is suspected to be linked to Parkinsonโs disease, a neurological disease of which the incidence doubled in the last 50 years. This disease, which used to be an old age pathology, now touches people in their thirties.
In 2003, Canesi et al showed that people with Parkinsonโs disease contaminated with a similar quantity of n-hexane and 2,5-hexanedione in their blood than a control group, had less capacity to eliminate it in their urine. The paper concluded that this lower ability to eliminate the 2,5-Hexanedione might be the reason why some people develop the Parkinson when others donโt.
Zhang et al. (2018) recently identified on rat model how the 2,5-hexandione can damage the brain cells which produce the dopamine.
Reproductive and endocrine disruptor effects
N-hexane and its toxic 2,5-hexanedione are reprotoxic in both male and female humans, laboratory animals and in vitro in explant tissue culture. N-hexane particularly reduces the fertility of both men and women. It can also affect embryos before birth (Cheng et al. 2012 and 2015). A recent literature review concludes that N-hexane and metabolite 2,5-HD should be classified as reprotoxin and endocrine disruptors.
The French ANSES classified n-hexane and 2,5-HD as presumed endocrine disruptors.