National Toxicology Program

National Toxicology Program
http://ntp.niehs.nih.gov/go/ts-10949-y

Testing Status of Acrylamide - 10949-Y

 

CASRN: 79-06-1

Formula: C3-H5-N-O

Synonyms/Common Names

  • 2-Propenamide

Known Uses

Polyacrylamides and dye intermediate Flocculants. Waste and water treatment. Paper and pulp industry (NLM/Dialog 1991). Associated with tobacco: reported either as a natural component of tobacco, pyrolysis product (in tobacco smoke), or additive for one or more types of tobacco products.

Chemical Properties

Toxicity Effects (HSDB)

Nomination Background

Short-Term Toxicity

  • 14 days (Dosed-Feed)  (C20313B)  Completed 
    • Rats: F344 (NCTR); Mice: B6C3F1/NCTR BR (C57BL/6N x C3H/HEN MTV-)
    • Dose: R&M: 0, 7.4, 18.5, 37, 74, 185, or 370 mg/acrylamide/kg bw.
  • 14 days (Dosed-Water)  (C20313)  Completed 
    • Rats: F344 (NCTR); Mice: B6C3F1/NCTR BR (C57BL/6N x C3H/HEN MTV-)
    • Dose: R&M: 0, 0.14, 0.35, 0.70, 1.41, 3.52, or 7.03 mM.
  • 90 days (Dosed-Feed)  (C20313B)  Completed 
    • Rats: F344 (NCTR); Mice: B6C3F1/NCTR BR (C57BL/6N x C3H/HEN MTV-)
    • Dose: R: 0, 18.5, 37, 74, or 185 mg/kg M: 0, 18.5, 37, 74, 185, or 370 mg/kg.
  • 90 days (Dosed-Water)  (C20313)  Completed 
    • Rats: F344 (NCTR); Mice: B6C3F1/NCTR BR (C57BL/6N x C3H/HEN MTV-)
    • Dose: R&M: 0, 0.14, 0.35, 0.70, 1.41, or 3.52 mM.

Long-Term Carcinogenicity

  • 2 years (Dosed-Water)  (C20313)  Report Complete 
    • TR-575 (NIH Number: 11-5917)  (Peer Review Approval 04/05/2011A )
      Toxicology and Carcinogenesis Studies of Acrylamide (CASRN 79-06-1) in F344/N Rats and B6C3F1 Mice (Feed and Drinking Water Studies)
    • Rats: F344 (NCTR); Mice: B6C3F1/NCTR BR (C57BL/6N x C3H/HEN MTV-)
    • Carcinogenesis Results
      • Male Rats Clear Evidence 
      • Female Rats Clear Evidence 
      • Male Mice Clear Evidence 
      • Female Mice Clear Evidence 
    • Dose: R&M: 0, 0.0875, 0.175, 0.35, or 0.70 mM.

Special Studies

  • Absorption Disposition Metabolism Elimination (Gavage)  (S0008)  Completed 
    • Citation: Miller MJ, Carter DE, Sipes IG. Pharmacokinetics of acrylamide in Fisher-344 rats. Toxicol Appl Pharmacol. 1982 Mar 30;63(1):36-44.Pubmed Abstract
    • Male Rats: F344/N
  • Mechanisms (Dosed-Feed; Dosed-Water; Gavage; Intraperitoneal Injection)  (S0866)  Completed 
    • Citation: Doerge DR, Young JF, McDaniel LP, Twaddle NC, Churchwell MI. Toxicokinetics of acrylamide and glycidamide in B6C3F1 mice. Toxicol Appl Pharmacol. 2005 Feb 1;202(3):258-67.Pubmed Abstract
    • Citation: Manière I, Godard T, Doerge DR, Churchwell MI, Guffroy M, Laurentie M, Poul JM. DNA damage and DNA adduct formation in rat tissues following oral administration of acrylamide. Mutat Res. 2005 Feb 7;580(1-2):119-29.Pubmed Abstract
    • Male and Female Rats: F344 (NCTR); Male and Female Mice: B6C3F1/NCTR BR (C57BL/6N x C3H/HEN MTV-); Male and Female Rats: F344 (NCTR); Male and Female Mice: B6C3F1/NCTR BR (C57BL/6N x C3H/HEN MTV-); Male and Female Mice: Tg.Lac1/C57BL/6 (Big Blue); Male and Female Rats: F344 (NCTR); Male and Female Mice: B6C3F1/NCTR BR (C57BL/6N x C3H/HEN MTV-); Male and Female Rats: F344 (NCTR); Male and Female Mice: B6C3F1/NCTR BR (C57BL/6N x C3H/HEN MTV-); Male and Female Mice: Tg.Lac1/C57BL/6 (Big Blue)
  • Other (Intraperitoneal Injection)  (S0772)  Completed 
    • Citation: Miller MS, Miller MJ, Burks TF, Sipes IG. Altered retrograde axonal transport of nerve growth factor after single and repeated doses of acrylamide in the rat. Toxicol Appl Pharmacol. 1983 Jun 15;69(1):96-101.Pubmed Abstract
    • Male Rats: Sprague Dawley; Male Mice: Swiss CD-1
  • Other (Dosed-Feed)  (S0773)  Completed 
    • Citation: Miller MJ, Miller MS, Burks TF, Sipes IG. A simple, sensitive method for detecting early peripheral nerve dysfunction in the rat following acrylamide treatment. Neurotoxicology. 1984 Summer;5(2):15-23.Pubmed Abstract
    • Male Rats: Sprague Dawley

Genetic Toxicology

  • Chromosome Aberrations  (549305)  Completed 
    • Mice
    •  Positive (Nonstandard Protocol) 
  • Comet Assay  (G10949C)  Completed 
    • Mice
  • In Vitro Cytogenetics (CA/SCE)  (279150)  Completed 
    • Sister Chromatid Exchange Positive 
    • Chromosome Aberrations Positive 
  • Drosophila  (675731)  Completed 
    • Citation: Foureman, P., Mason, J.M., Valencia, R., Zimmering, S. Chemical Mutagenesis Testing in Drosophila. X. Results of 70 coded compounds tested for the National Toxicology Program. Environ. Molec. Mutagen. Vol. 23 (1994) 208-227
    • Reciprocal Translocation/Sex-Linked Recessive Lethal Negative 
  • Micronucleus  (A75648)  Completed 
    • Citation: Witt KL, Livanos E, Kissling GE, Torous DK, Caspary W, Tice RR, Recio L. Comparison of flow cytometry- and microscopy-based methods for measuring micronucleated reticulocyte frequencies in rodents treated with nongenotoxic and genotoxic chemicals. Mutat Res. 2008 Jan 8;649(1-2):101-13. Epub 2007 Aug 11.
    • Mice: B6C3F1
    • Male Positive 
    • Female NA 
  • Micronucleus  (A97370)  Completed 
    • Citation: Witt KL, Livanos E, Kissling GE, Torous DK, Caspary W, Tice RR, Recio L. Comparison of flow cytometry- and microscopy-based methods for measuring micronucleated reticulocyte frequencies in rodents treated with nongenotoxic and genotoxic chemicals. Mutat Res. 2008 Jan 8;649(1-2):101-13. Epub 2007 Aug 11.
    • Rats: Fischer 344
    • Male Equivocal 
    • Female NA 
  • Micronucleus  (F12535)  Completed 
    • Citation: Ghanayem BI, Witt KL, Kissling GE, Tice RR, Recio L. Absence of acrylamide-induced genotoxicity in CYP2E1-null mice: evidence consistent with a glycidamide-mediated effect. Mutat Res. 2005 Oct 15;578(1-2):284-97.
    • Mice: 129 Sv/Ev
    • Female Positive 
  • Micronucleus  (F75142)  Completed 
    • Citation: Ghanayem BI, Witt KL, Kissling GE, Tice RR, Recio L. Absence of acrylamide-induced genotoxicity in CYP2E1-null mice: evidence consistent with a glycidamide-mediated effect. Mutat Res. 2005 Oct 15;578(1-2):284-97.
    • Mice: 129 Sv/Ev
    • Female Negative 
  • Micronucleus  (F75648)  Completed 
    • Citation: Witt KL, Livanos E, Kissling GE, Torous DK, Caspary W, Tice RR, Recio L. Comparison of flow cytometry- and microscopy-based methods for measuring micronucleated reticulocyte frequencies in rodents treated with nongenotoxic and genotoxic chemicals. Mutat Res. 2008 Jan 8;649(1-2):101-13. Epub 2007 Aug 11.
    • Mice: B6C3F1
    • Male Positive 
  • Micronucleus  (F97370)  Completed 
    • Citation: Witt KL, Livanos E, Kissling GE, Torous DK, Caspary W, Tice RR, Recio L. Comparison of flow cytometry- and microscopy-based methods for measuring micronucleated reticulocyte frequencies in rodents treated with nongenotoxic and genotoxic chemicals. Mutat Res. 2008 Jan 8;649(1-2):101-13. Epub 2007 Aug 11.
    • Rats: Fischer 344
    • Male Negative 
  • Micronucleus  (G10949)  Completed 
    • Mice: C57BL/6
    • Male Positive 
  • Micronucleus  (G10949D)  Completed 
    • Mice
  • Salmonella  (440483)  Completed 
    • Citation: Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K, Speck W. Salmonella mutagenicity tests: III. Results from the testing of 255 chemicals. Environ Mutagen. 1987;9 Suppl 9:1-109.
    •  Negative 
  • Salmonella  (965355)  Completed 
    • Citation: Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K, Speck W. Salmonella mutagenicity tests: III. Results from the testing of 255 chemicals. Environ Mutagen. 1987;9 Suppl 9:1-109.
    •  Weakly Positive 
  • Sister Chromatid Exchanges  (549305)  Completed 
    • Mice
    • Sister Chromatid  Positive 

Organ Systems Toxicity

  • Dominant Lethal (Male) (Dosed-Feed)  (DLM005)  Completed 
    • Citation: Gutierrez-Espeleta, G.A., Hughes, L.A., Piegorsch, W., Shelby, M.D., and Generoso, W.M. Acrylamide: Dermal Exposure Produces Genetic Damage in Male Mouse Germ Cells. Fund. Appl. Tox. 18: 189-192 (1992).
    • Citation: Shelby, M.D., Cain, K.T., Hughes, L.A., Braden, P.W., and Generoso, W.M. Dominant lethal effects of acrylamide in male mice. Mutation Res. 173:35-40 (1986).
    • Male Mice: C3H X 101
    • Mice Male Positive 
  • Heritable Translocation Test (Dosed-Feed)  (HTM31)  Completed 
    • Citation: Shelby, M.D., Cain, K.T., Cornett, C.V., and Generoso, W.M. (1987) Acrylamide: Induction of heritable translocations in male mice. Environ. Mutagen. 9:363-368 (1987).
    • Male Mice: C3H X 101
    • Mice Male Positive 
  • Morphological Specific Locus (Dosed-Water)  (MSLM41)  Completed 
    • Citation: Russell, L.B., Hunsicker, P., Cacheiro, N.L.A., and Generoso, W.M. Induction of specific-locus mutations in the germ cells of the mouse by acrylamide monomer. Mutation Res. 262:101-107 (1991).
    • Male Mice: 101 X C3H
    • Mice Male Positive 
  • Phase 1: 3 and 6 months; phase 2: 12 and 24 months Neurotoxicology Assessment (Gavage)  (NTA20401)  Report Draft 
    • Male and Female Rats: F344 (NCTR)
    • Dose: In utero (GD 6-21); gavage: PND 1-21; wean: PND 22 -- drinking water.
  • Neurotoxicology Assessment (Gavage)  (NTA94001)  Completed 
    • Citation: Animal Neurobehavioral Test Battery in NTP Assessment In: Advances in Neurobehavioral Toxicology: Applications in Environmental & Occupational Health (Barry L. Johnson, ED.), Lewis Publishers, Inc. pp. 403-418 (1990).
    • Male Rats: F344/N
  • Preimplantation Zygote Effects (Dosed-Water)  (PZEF47)  Completed 
    • Citation: Rutledge, J.C., Generoso, W.M., Shourbaji, A., Cain, K.T., Gans, M., and Oliva, J. Developmental anomalies derived from exposure of zygotes and first-cleavage embryos to mutagens. Mutation Research 296: 167-177 (1992).
    • Female Mice: C3H X C57BL
    • Mice Female Positive 
  • 27 weeks Continuous Breeding (Legacy) (Dosed-Water)  (RACB90022)  Completed 
    • Citation: Final Report on the Reproductive Toxicity of Acrylamide in CD-1 Swiss Mice
    • Male and Female Mice: Swiss
    • Dose: 0,60,120,240,300,360 PPM; 0,10,30 PPM; 0,30 PPM; 0,3,10,30 PPM.
  • 6 to 20 GD Conventional Teratology (Gavage)  (TER88048)  Completed 
    • Citation: Teratologic Evaluation of Acrylamide Administered to Sprague-Dawley (CD) Rats on Gestational Days 6 through 20
    • Female Rats: Sprague Dawley
    • Rats Maternal Negative 
    • Rats Fetal Negative 
    • Dose: 0, 2.5, 7.5, 15 MG/KG/DAY.
  • 6 to 17 GD Conventional Teratology (Gavage)  (TER89049)  Completed 
    • Citation: Teratologic Evaluation of Acrylamide Administered to CD-1 Mice on Gestational Days 6 through 17
    • Female Mice: Swiss
    • Mice Maternal Positive 
    • Mice Fetal Positive 
    • Dose: 0, 3, 15, 45 MG/KG/DAY.
  • Total Reproductive Capacity (Dosed-Water)  (TRC98001)  Completed 
    • Citation: Bishop, JB, Morris, RW, Seely, JC, Hughes, LA, Cain, KT, Generoso, WM. Alterations in the Reproductive Patterns of Female Mice Exposed to Xenobiotics. Fund. and Appl. Tox. 40: 191-204 (1997).
    • Female Mice
    • Mice Female Negative 
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