Acrylamide does not induce tumorigenesis or major defects in mice in vivo

Abstract

Chronic administration of acrylamide has been shown to induce thyroid tumors in rat. In vitro acrylamide also causes DNA damage, as demonstrated by the comet assay, in various types of cells including human thyroid cells and lymphocytes, as well as rat thyroid cell lines. In this work, mice were administered acrylamide in their drinking water in doses comparable with those used in rats, i.e., around 3-4 mg/kg per day for mice treated 2, 6, and 8 months. Some of the mice were also treated with thyroxine (T 4 ) to depress the activity of the thyroid. Others were treated with methimazole that inhibits thyroid hormone synthesis and consequently secretion and thus induces TSH secretion and thyroid activation. These moderate treatments were shown to have their known effect on the thyroid (e.g. thyroid hormone and thyrotropin serum levels, thyroid gland morphology.). Besides, T 4 induced an important polydipsia and degenerative hypertrophy of adrenal medulla. Acrylamide exerted various discrete effects and at high doses caused peripheral neuropathy, as demonstrated by hind-leg paralysis. However, it did not induce thyroid tumorigenesis. These results show that the thyroid tumorigenic effects of acrylamide are not observed in another rodent species, the mouse, and suggest the necessity of an epidemiological study in human to conclude on a public health policy.

Scientific Opinion on acrylamide in food

“…over 8 months did not result in tumours in the organs inspected histopathologically (pituitary, thyroid, and adrenal glands, reproductive tract) (Jin et al, 2008).…”

“…Treatment of female CD1 rats (20 animals) with AA in the drinking water (leading to a daily oral dose of 3-4 mg/kg b.w.) over 8 months did not result in tumours in the organs inspected histopathologically (pituitary, thyroid, and adrenal glands, reproductive tract) (Jin et al, 2008).…”

“…The motor protein kinesin is another example for a protein targeted by AA since microtubule-binding of kinesin, an element of microtubule motility in neurons, spermatids etc., was inhibited by 100 µM AA (Sickles et al, 2007), GA being more potent than AA. Kinesin-mediated microtubule motility is can be inhibited by both AA and GA in vitro (Friedman et al, 2008).…”

“…Kinesin-mediated microtubule motility is can be inhibited by both AA and GA in vitro (Friedman et al, 2008). …”

“…Furthermore, distinct changes in expression patterns of testicular soluble guanylate caclase (sGC) heterodimers were observed in AA-treated rats. Friedman et al (2008) suggested that inhibition of nuclear kinesin is responsible for AA-induced clastogenicity and aneuploidy in isolated rat testicular cells. Two kinesin motors, KIFC5A and KRP2, which are responsible for spindle assembly and disassembly of kinetochore microtubules, were inhibited by AA.…”