Acrylamide: Induction of heritable translocations in male mice

Shelby, Michael D.; Cain, K.T.; Cornett, C.V.; Generoso, W.M.

doi:10.1002/em.2860090403

Cited by 88 publications

(40 citation statements)

References 15 publications

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“…The frequencies of dead implants per female are increased with both modes of exposure during the first three mating intervals, which represent sperm and late spermatids. This pattern of sensitivity is in accord with previous publications (Shelby et al, 1986(Shelby et al, , 1987Smith et al, 1986, Holland et al, 1999. The dominant lethal effects are illustrated in Fig.…”

Section: Statisticssupporting

confidence: 80%

“…Using flow cytometer-based analyses, it was demonstrated that the dose-response relationship for AA-induced micronuclei in mouse bone marrow cells was linear down to low single doses of 1-30 mg/kg AA applied by intraperitoneal (ip) injection (Abramsson-Zetterberg, 2003). In rodent germ cells, dominant lethal mutations and heritable translocations were induced by ip injection with AA in late spermatids and sperm (Adler, 1990;Shelby et al, 1986Shelby et al, , 1987Smith et al, 1986). Analysis of structural chromosome aberra-tions in one-cell embryos after paternal AA-treatment was performed using conventional and molecular techniques (Pacchierotti et al, 1994;Marchetti et al, 1997).…”

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confidence: 99%

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Heritable translocations induced by dermal exposure of male mice to acrylamide

Adler¹,

Gonda²,

Angelis³

et al. 2004

Cytogenet Genome Res

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Acrylamide (AA) is an important industrial chemical used mainly in the production of polymers. It can be absorbed through the skin. AA was shown to be a germ cell clastogen that entails a genetic risk for exposed workers. The genetic risk calculation was based on mouse heritable translocation test data obtained after acute intraperitoneal (ip) exposure (Adler et al., 1994). To obtain a correction factor between ip and dermal exposure, dominant lethal and heritable translocation tests were carried out with dermal exposure of male mice to AA. In the dominant lethal test, male (102/El × C3H/El)F₁ mice were exposed by dermal application to the shaved backs of 50 mg/kg AA per day on five consecutive days or to five daily ip injections of 50 mg/kg AA. One day after the end of exposure, the males were mated to untreated females of the same hybrid stock for four days and females were changed every four days for a total of five matings. Dominant lethal effects were found during matings 1–3. For ip exposure, these values were 81.7, 85.7 and 45.4%, respectively; for dermal exposure the corresponding values were 22.1, 30.6 and 16.5%, respectively. In the heritable translocation assay, male C3H/El mice were treated with five dermal exposures of 50 mg/kg AA and mated 1.5–8.5 days after the end of exposure to untreated female 102/El mice. Pregnant females were allowed to come to term and all offspring were raised to maturity. Translocation carriers among the F₁ progeny were selected by a sequential fertility testing and cytogenetic analysis including G-band karyotyping and M-FISH. A total of 475 offspring were screened and 41 translocation carriers were identified. The observed translocation frequency after dermal exposure was 8.6% as compared to 21.9% after similar ip exposure (Adler, 1990). The calculated ratio of ip vs. dermal exposure of 0.39 can be applied to obtain a more realistic calculation of genetic risk for dermally exposed workers.

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Section: Statisticssupporting

confidence: 80%

mentioning

confidence: 99%

Heritable translocations induced by dermal exposure of male mice to acrylamide

Adler¹,

Gonda²,

Angelis³

et al. 2004

Cytogenet Genome Res

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“…Favor and Shelby (2005) reviewed seven published studies that assessed the effectiveness of AA and GA in inducing transmitted reciprocal translocations or gene mutations in the mouse. Results indicated an increase in the frequency of translocation carriers in offspring following paternal exposure to AA or GA in spermatid and spermatozoa (Shelby et al, 1987;Adler, 1990;Adler et al, 1994Adler et al, , 2004Generoso et al, 1996). Even the dose of 50 mg AA/kg b.w.…”

Section: Genotoxicitymentioning

confidence: 99%

Scientific Opinion on acrylamide in food

Publication¹

2015

EFS2

329

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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“…The National Toxicology Program (NTP) has taken a prominent role in the identification of genetic hazards in the environment and in the acquisition ofdata that are used by regulatory agencies in assessing genetic risks to human health. For example, NTP-sponsored germ-cell mutagenesis studies have been responsible for the identification of acrylamide as a reproductive hazard (21)(22)(23), and dose-response and dose-rate data on ethylene oxide have been used by the EPA in their hazard assessment efforts. The evaluation of various aspects of germ-cell mutagenesis such as dose, dose rate, sex, and strain effects; investigations of mutation induction in cells such as oocytes and zygotes; and identification of models of human genetic diseases such as those for j-thalassemia (26,27) and carbonic anhydrase-2 deficiency (28) are among the contributions made to the understanding of mammalian germ-cell mutagenesis.…”

Section: The Human Health Issuementioning

confidence: 99%

Fertility, reproduction, and genetic disease: studies on the mutagenic effects of environmental agents on mammalian germ cells.

Shelby

Bishop

Mason

et al. 1993

Environ Health Perspect

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Because geneticaly based diseases have a major inpact on human health, the National Institute of Environmental Health Sciences (NIEHS) has conducted a research and testing program for more than a decade to address chemical induction of heritable genetic damage in the germ cells of mammals. Although most genetic disease results from preexisting mutations, a portion is due to the occurrence ofnew mutations. The supposition that exposure to mutagenic c s contributes to the occurrence of new mutations in the human population is strongly supported by the results from animal models. Such studies clearly demonstrate the potential ofemnironmental chemicals to induce mutations in both somatic and reproductive cells of mammals. This NIEHS program has become a leader in the identification ofgenetic hazards in the environment and in the acquisition of animal model data used by regulatory agencies in assessing genetic risks to human health.

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Acrylamide: Induction of heritable translocations in male mice

Cited by 88 publications

References 15 publications

Heritable translocations induced by dermal exposure of male mice to acrylamide

Heritable translocations induced by dermal exposure of male mice to acrylamide

Scientific Opinion on acrylamide in food

Fertility, reproduction, and genetic disease: studies on the mutagenic effects of environmental agents on mammalian germ cells.

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