The effects of subchronic acrylamide exposure on gene expression, neurochemistry, hormones, and histopathology in the hypothalamus–pituitary–thyroid axis of male Fischer 344 rats

Bowyer, John F.; Latendresse, John R.; Delongchamp, Robert R.; Muskhelishvili, Levan; Warbritton, Alan; Thomas, M. Joy; Tareke, Eden; McDaniel, L. Patrice; Doerge, Daniel R.

doi:10.1016/j.taap.2008.02.028

Cited by 47 publications

(32 citation statements)

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“…Three publications have used internal dosimetry simulations from PBPK models for risk assessment of neurotoxicity and cancer in an effort to reduce uncertainty in extrapolating across dose and species from animal toxicity testing to humans exposed to AA in the diet (Doerge et al, 2008;Tardiff et al, 2010;DeWoskin et al, 2013).…”

Section: Use Of Pbpk Modelling For Human Cancer and Neuropathy Risk Amentioning

confidence: 99%

“…Dose-response analysis of these data by Doerge et al (2008) provided BMDL 10 values of 0.65 mg/kg b.w. per day for males and 0.60 mg/kg b.w.…”

Section: Dose-response Assessmentmentioning

confidence: 99%

“…This caused Watzek et al (2012a) to assume that small amounts of AA may be formed endogenously. Tareke et al (2009) reported the formation of AA when the amino acid asparagine was incubated with hydrogen peroxide and another study has shown that Hb adducts of AA are increased in mice treated with compounds known to induce free radicals (Tareke et al, 2008). The CONTAM Panel noted that methodological deficiencies in the Tareke et al (2008Tareke et al ( , 2009 studies precluded conclusions regarding endogenous formation.…”

mentioning

confidence: 99%

“…Tareke et al (2009) reported the formation of AA when the amino acid asparagine was incubated with hydrogen peroxide and another study has shown that Hb adducts of AA are increased in mice treated with compounds known to induce free radicals (Tareke et al, 2008). The CONTAM Panel noted that methodological deficiencies in the Tareke et al (2008Tareke et al ( , 2009 studies precluded conclusions regarding endogenous formation. As an alternative to the endogenous formation of AA, the possibility should be considered that adducts of AA with cysteine in dietary proteins are present in food and feed, which may be absorbed from the GI tract after proteolytic degradation and subsequently excreted in urine.…”

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confidence: 99%

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Scientific Opinion on acrylamide in food

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2015

EFS2

292

170

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EFSA was asked to deliver a scientific opinion on acrylamide (AA) in food. AA has widespread uses as an industrial chemical. It is also formed when certain foods are prepared at temperatures above 120 °C and low moisture, especially in foods containing asparagine and reducing sugars. The CONTAM Panel evaluated 43 419 analytical results from food commodities. AA was found at the highest levels in solid coffee substitutes and coffee, and in potato fried products. Mean and 95th percentile dietary AA exposures across surveys and age groups were estimated at 0.4 to 1.9 µg/kg body weight (b.w.) per day and 0.6 to 3.4 µg/kg b.w. per day, respectively. The main contributor to total dietary exposure was generally the category 'Potato fried products (except potato crisps and snacks)'. Preferences in home-cooking can have a substantial impact on human dietary AA exposure. Upon oral intake, AA is absorbed from the gastrointestinal tract and distributed to all organs. AA is extensively metabolised, mostly by conjugation with glutathione but also by epoxidation to glycidamide (GA). Formation of GA is considered to represent the route underlying the genotoxicity and carcinogenicity of AA. Neurotoxicity, adverse effects on male reproduction, developmental toxicity and carcinogenicity were identified as possible critical endpoints for AA toxicity from experimental animal studies. The data from human studies were inadequate for dose-response assessment. The CONTAM Panel selected BMDL 10 values of 0.43 mg/kg b.w. per day for peripheral neuropathy in rats and of 0.17 mg/kg b.w. per day for neoplastic effects in mice. The Panel concluded that the current levels of dietary exposure to AA are not of concern with respect to non-neoplastic effects. However, although the epidemiological associations have not demonstrated AA to be a human carcinogen, the margins of exposure (MOEs) indicate a concern for neoplastic effects based on animal evidence. © European Food SUMMARYFollowing a request from the European Commission, the Panel on Contaminants in the Food Chain (CONTAM Panel) was asked to deliver a scientific opinion on acrylamide (AA) in food. The Panel developed the draft scientific opinion which underwent a public consultation from 1 July 2014 to 15 September 2014. The comments received and how they were taken into account when finalising the scientific opinion were published in an EFSA Technical Report (EFSA, 2015).AA is a low molecular weight, highly water soluble, organic compound. It is used inter alia as an industrial chemical and in the production of polyacrylamides. Heightened concerns about exposure to AA arose in 2002 when it was discovered that it forms when certain foods are prepared at temperatures usually above 120 °C and low moisture. It forms, at least in part, due to a Maillard reaction between certain amino acids, such as asparagine, and reducing sugars. However, several other pathways and precursors have also been proposed to contribute to AA formation. AA forms in numerous baked or fried carbohydrate-rich f...

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Section: Use Of Pbpk Modelling For Human Cancer and Neuropathy Risk Amentioning

confidence: 99%

“…Dose-response analysis of these data by Doerge et al (2008) provided BMDL 10 values of 0.65 mg/kg b.w. per day for males and 0.60 mg/kg b.w.…”

Section: Dose-response Assessmentmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Scientific Opinion on acrylamide in food

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2015

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292

170

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“…Previous studies have demonstrated that the GST-Pi mRNA gene expression increased significantly in hypophysis when rats were exposed to acrylamide at doses of 2.5 mg, 10 mg, and 50 mg/kg b.w. daily via drinking water (Bowyer et al, 2008). It could be stated that an increased GST-Pi mRNA gene expression in the AA group might be the reason for oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Amelioration of subchronic acrylamide toxicity in large intestine of rats byorganic dried apricot intake

Erdemli¹,

Doğan²,

Çiğremiş³

et al. 2015

Turk J Biol

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IntroductionAcrylamide (AA) is a carcinogenic chemical that causes cancer in many experimental animal organs after chronic exposure (Johnson et al., 1986). AA also has neurotoxic, mutagenic, and genotoxic effects in humans and experimental animals (Dearfield et al., 1995;LoPachin et al., 2003). Human nutrients that are prepared by cooking at high temperatures could cause high levels of AA formation. AA is a water soluble chemical and it is absorbed and distributed in animals and humans throughout the whole body. AA has been used in the industrial sector, including clarifying drinking water, treating municipal and industrial wastewaters, and in polyacrylamide gels in biotechnology laboratories since 1958 (IARC, 1995). Exposure to AA in humans may occur via ingestion, dermal contact, and inhalation of AA or AA-containing products such as processed food. AA is especially generated in carbohydrate-rich foods at 120 °C and higher by reacting with asparagines and sugar (Lindsay, 2002). The formation of AA in food involves Maillard reactions of asparagine and reducing sugars (Mottram et al., 2002). This fact is an important reason for acrylamide studies (Tareke et al., 2002) Apricot (Prunus armeniaca L.) has antioxidant properties due to its flavonoid and carotenoid content (Vardi et al., 2008). Apricot is one of the most important dietary sources of carotenoids and one among the Malatya apricot varieties, Kabaası, has the highest total carotenoid content (Akin et al., 2008). Flavonoids are primarily found in vegetables, fruits, red wine, green tea, and onions (Mansuri et al., 2014). Many agriculture products provide natural melatonin in the diet. Melatonin is a direct scavenger Abstract: Acrylamide (AA) has neurotoxic, mutagenic, and genotoxic effects in humans and experimental animals. Fruit consumption is important for human health, because fruits are the source of many nutrients such as vitamins, minerals, carotenoids, dietary fiber, and phytonutrients. Many agricultural products provide natural melatonin in the diet. At the onset of the study, rats were weighted and randomly divided into four groups each containing 10 rats as follows: group 1: control (fed with normal diet and normal drinking water); group 2: apricot (fed with a daily diet with 5% apricot and normal drinking water); group 3: AA (administered daily acrylamide at 500 µg/kg b.w. via drinking water and fed a normal diet); group 4: apricot-AA (administered daily acrylamide at 500 µg/kg b.w. via drinking water and fed with a diet with 5% apricot). The diet schedule was continued for 12 weeks. At the end of the study, samples of large intestine were collected for biochemical analyses. The highest lipid peroxidation (as malondialdehyde, MDA) levels were observed in the AA groups, but MDA levels decreased significantly (P < 0.05) with apricot intake. Glutathione peroxidase activity in the apricot-AA group was higher than in the other three groups (P < 0.05). Glutathione S-transferase (GST) enzyme activity increased significantly in the AA group as compared ...

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Juvenile rats do not exhibit elevated sensitivity to acrylamide toxicity after oral administration for 12 weeks

Takami

Imai

Cho

et al. 2011

J of Applied Toxicology

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Acrylamide (AA), a neurotoxic, testicular toxic, genotoxic and carcinogenic chemical, has been reported to be formed in processed food, and sensitivity to AA intoxication in childhood is a concern. In the present study, to clarify the general toxicological profile of AA in juvenile rats, subchronic toxicity was evaluated in F344 rats administered AA in the drinking water at 0 (control), 10, 20 and 40 ppm, presented to the dams (three per group) immediately after the birth of their litters, through lactation (3 weeks), and directly to the offspring in their drinking water after weaning for a further 9 weeks (12 weeks total). Treatment with AA caused a decrease in body weights in 20 and 40 ppm F(1) females, compared with the controls. Average AA intake throughout the treatment period for the 10, 20 and 40 ppm groups after weaning was equivalent to 1.0, 2.1 and 4.4 mg kg(-1) body weight per day, respectively, in males and 1.2, 2.5 and 4.9 mg kg(-1) body weight per day, respectively, in females. No toxicologically significant organ weight changes were observed. AA-induced histopathological changes were limited to focal degeneration and necrosis of the seminiferous epithelium in the testes and desquamated epithelium in the ducts of epididymides, noted only in 40 ppm males. Taken together with previous reports, juvenile rats are not necessarily more susceptible to AA-induced toxicity as compared with young adults.

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The effects of subchronic acrylamide exposure on gene expression, neurochemistry, hormones, and histopathology in the hypothalamus–pituitary–thyroid axis of male Fischer 344 rats

Cited by 47 publications

References 31 publications

Scientific Opinion on acrylamide in food

Scientific Opinion on acrylamide in food

Amelioration of subchronic acrylamide toxicity in large intestine of rats byorganic dried apricot intake

Juvenile rats do not exhibit elevated sensitivity to acrylamide toxicity after oral administration for 12 weeks

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