**3.2 Genotoxicity, carcinogenicity and mutagenicity**

When the nervous systems of humans and animals are exposed to excessive quantities of ACR, α, β unsaturated carbonyl molecule with strong chemical activity, it can cause cancer and neurotoxicity [23]. ACR and its metabolites have been shown to be both genotoxic and carcinogenic in various studies [24, 25]. When ACR enters the body, it is oxidised and transformed into the genotoxic metabolite glycidamide (GA) [26]. ACR is ingested in the digestive system and transported to the liver at a rate of 4 mol ACR per 1 mol haemoglobin, where it is processed and destroyed by two distinct routes. The carcinogenic action of ACR, which is metabolised to GA in the liver by CYP2E1, has a mutagenic effect in the brain, kidneys, lungs, uterus, and testis in several organisms that includes experimental animals as well [27]. It was discovered that the genotoxic effect on DNA was mostly caused by GA, an ACR metabolite, rather than ACR itself [28]. The conversion of ACR to GA was found to be quite common in rats and mice, and it's mode of action included it's interaction with purine bases in the liver, renal, and pulmonary DNAs of rats and mice, causing genotoxic impacts [24, 25]. ACR also induced gene mutations and chromosomal defects in cultured mouse embryonic fibroblast cells, according to in vitro experiments [29, 30].

In this chapter, we have focused on neurotoxic effects caused by ACR in rats. ACR is predominantly known as a neurotoxin in humans. In this chapter, we are discussing ACR induced neurotoxicity in rat models where extensive studies have been done.
