Factors associated with reduced fertility and implantation rates in females mated to acrylamide- treated rats

Sublet, Virginia; Zenick, Harold; Smith, Milton T.

doi:10.1016/0300-483x(89)90174-1

Cited by 34 publications

(22 citation statements)

References 13 publications

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“…Published studies from this laboratory, as well as others, have demonstrated a positive dose-response correlating an increasing percentage of resorptions per litter (an indication of dominant lethality), with escalating doses of AA (0-60 mg kg À1 day À1 ) administered intraperitoneally or by gavage [21,23,30]. The current dosage was chosen based on results from oral disposition studies conducted in our laboratory demonstrating enzyme saturation following daily gavage with AA at doses higher than 25 mg kg À1 day À1 .…”

Section: Comparison Of the Reproductive Toxicity Of Aa In Lean And Obmentioning

confidence: 96%

Diet-Induced Obesity in Male Mice Is Associated with Reduced Fertility and Potentiation of Acrylamide-Induced Reproductive Toxicity1

Ghanayem

Bai

Kissling

et al. 2010

Biology of Reproduction

176

127

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The prevalence of human obesity and related chronic disorders such as diabetes, cardiovascular diseases, and cancer is rapidly increasing. Human studies have shown a direct relationship between obesity and infertility. The objective of the current work was to examine the effect of diet-induced obesity on male fertility and the effect of obesity on susceptibility to chemical-induced reproductive toxicity. From 5 to 30 wk of age, genetically intact male C57Bl/6J mice were fed a normal diet or one in which 60% of the kilocalories were from lard. Obese mice exhibited significant differences in the mRNA of several genes within the testes in comparison to lean males. Pparg was increased 2.2-fold, whereas Crem, Sh2b1, Dhh, Igf1, and Lepr were decreased 6.7, 1.4, 3.2, 1.6, and 7.2-fold, respectively. The fertility of male mice was compared through mating with control females. Acrylamide (AA)-induced reproductive toxicity was assessed in obese or lean males treated with water or 25 mg AA kg(-1) day(-1) via gavage for 5 days and then mated to control females. Percent body fat and weight were significantly increased in mice fed a high-fat vs. a normal diet. Obesity resulted in significant reduction in plugs and pregnancies of control females partnered with obese vs. lean males. Serum leptin and insulin levels were each approximately 5-fold higher in obese vs. age-matched lean mice. Sperm from obese males exhibited decreased motility and reduced hyperactivated progression vs. lean mice. Treatment with AA exacerbated male infertility of obese and lean mice; however, this effect was more pronounced in obese mice. Further, females partnered with AA-treated obese mice exhibited a further decrease in the percentage of live fetuses, whereas the percentage of resorptions increased. This work demonstrated that diet-induced obesity in mice caused a significant reduction in male fertility and exacerbated AA-induced reproductive toxicity and germ cell mutagenicity.

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Section: Comparison Of the Reproductive Toxicity Of Aa In Lean And Obmentioning

confidence: 96%

Diet-Induced Obesity in Male Mice Is Associated with Reduced Fertility and Potentiation of Acrylamide-Induced Reproductive Toxicity1

Ghanayem

Bai

Kissling

et al. 2010

Biology of Reproduction

176

127

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“…However, it significantly depressed pup body weight at birth and weight gain during lactation through post-weaning . Sublet et al (1989) reported statistically significantly decreased sperm mobility in Long-Evans rats administered AA by gavage at dose levels of 45 mg/kg b.w. per day for 5 days, but suggested that this effect was not solely responsible for poorer reproductive performance.…”

Section: Discussionmentioning

confidence: 99%

“…Based upon the concordance of tumour sites between AA and GA, it can be concluded that carcinogenic activity of AA is due to its metabolic conversion to GA. (2012). These previous evaluations referred to several studies reporting on the reproductive and developmental toxicity of orally administered AA Sakamoto and Hashimoto, 1986;Smith et al, 1986;Working et al, 1987;Sublet et al, 1989;Chapin et al, 1995;Tyl et al, 2000a,b). AA did not significantly affect mating performance in female rats, e.g.…”

Section: Discussionmentioning

confidence: 99%

“…The male-mediated infertility was selected as the critical effect for acuteduration oral exposure (14 days or less), and a Minimal Risk Level was derived based on results of fertility testing of male rats administered AA by gavage for five days prior to one week mating sessions with untreated female rats (Sublet et al, 1989). PBPK modelling (Sweeney et al, 2010) and BMD analysis were performed to predict a HED of 0.31 mg/kg per day, that was divided by an uncertainty factor of 30 (3 for interspecies extrapolation using a PBPK model and 10 for human variability), resulting in an acute-duration oral Minimal Risk Level of 0.01 mg/kg per day.…”

Section: Previous Risk Assessmentsmentioning

confidence: 99%

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Scientific Opinion on acrylamide in food

Publication¹

2015

EFS2

334

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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“…2001) i mutagenne działanie akrylamidu na komórki rozrodcze (Dearfield i in. 1995;Sublet i in. 1989), zaleca się w ACGIH przyjęcie za wartość 8-h TLV--TWA dla frakcji wdychalnej i par stężenie akrylamidu wynoszące 0,03 mg/m 3 (ACGIH 2005).…”

Section: Istniejące Wartości Nds I Ich Podstawyunclassified

[b]Akrylamid.[/b] Dokumentacja proponowanych dopuszczalnych wielkości narażenia zawodowego

Sapota¹,

Skrzypińska-Gawrysiak²

2014

PiMOSP

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Factors associated with reduced fertility and implantation rates in females mated to acrylamide- treated rats

Cited by 34 publications

References 13 publications

Diet-Induced Obesity in Male Mice Is Associated with Reduced Fertility and Potentiation of Acrylamide-Induced Reproductive Toxicity1

Diet-Induced Obesity in Male Mice Is Associated with Reduced Fertility and Potentiation of Acrylamide-Induced Reproductive Toxicity1

Scientific Opinion on acrylamide in food

[b]Akrylamid.[/b] Dokumentacja proponowanych dopuszczalnych wielkości narażenia zawodowego

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