National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/18983

Target Organs and Levels of Evidence for GMM-11

Toxicology Studies of Dichloroacetic Acid (CASRN 79-43-6) in Genetically Modified (FVB Tg.AC Hemizygous) Mice (Dermal and Drinking Water Studies) and Carcinogenicity Studies of Dichloroacetic Acid in Genetically Modified [B6.129-Trp53tm1Brd (N5) Haploinsufficient] Mice (Drinking Water Studies)

Chemical (Study Title)
CASRN
Peer Review Date Primary Uses Route/Exposure Levels Study Laboratory
Water disinfection model (Dichloroacetic acid)
79-43-6
09/27/2005 Breakdown product of drinking water disinfectants, astringent, use in treatment of lactic acidosis, keratolytic agent (Merck 1989) special initiative using the transgenic mouse model for method development. 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. Topical Application 0, 31.25, 125, or 500 mg/kg Battelle Columbus Laboratory

Levels of evidence information for Carcinogenesis and Genetic Toxicology Studies in Tg.AC Hemizygous Mice in the Dermal Studies of Dichloroacetic Acid
  Male Tg.AC Hemizygous Mice Female Tg.AC Hemizygous Mice
  26 Weeks 39 Weeks 26 Weeks 39 Weeks
Neoplastic Lesions None
  • Skin (site of application): squamous cell papilloma 0/10 0/10 2/10 8/10
None
  • Skin (site of application): squamous cell papilloma 0/10 0/10 0/10 6/10
Non-Neoplastic Lesions
  • Kidney: nephropathy
  • Liver: hepatocyte cytoplasmic vacuolization; increased severity of hepatocyte cytoplasmic vacuolization
  • Skin (site of application): epidermal hyperkeratosis; epidermal hyperplasia
  • Kidney: nephropathy
  • Liver: hepatocyte cytoplasmic vacuolization; increased severity of hepatocyte cytoplasmic vacuolization
  • Skin (site of application): epidermal hyperkeratosis; epidermal hyperplasia
  • Liver: hepatocyte cytoplasmic vacuolization; increased severity of hepatocyte cytoplasmic vacuolization
  • Skin (site of application): epidermal hyperkeratosis; epidermal hyperplasia
  • Liver: hepatocyte cytoplasmic vacuolization; increased severity of hepatocyte cytoplasmic vacuolization
  • Skin (site of application): epidermal hyperkeratosis; epidermal hyperplasia




Chemical (Study Title)
CASRN
Peer Review Date Primary Uses Route/Exposure Levels Study Laboratory
Water disinfection model (Dichloroacetic acid)
79-43-6
09/27/2005 Breakdown product of drinking water disinfectants, astringent, use in treatment of lactic acidosis, keratolytic agent (Merck 1989) special initiative using the transgenic mouse model for method development. 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. Dosed-Water
0, 500, 1000, or 2000 mg/L
Battelle Columbus Laboratory

Levels of evidence information for Carcinogenesis and Genetic Toxicology Studies in Tg.AC Hemizygous Mice in the Drinking Water Studies of Dichloroacetic Acid
  Male Tg.AC Hemizygous Mice Female Tg.AC Hemizygous Mice
  26 Weeks 41 Weeks 26 Weeks 41 Weeks
Neoplastic Lesions
  • Lung: alveolar/bronchiolar carcinoma 0/15 0/15 1/15 0/15
  • Lung: alveolar/bronchiolar adenoma 1/10 2/10 7/10 3/10
  • Lung: alveolar/bronchiolar carcinoma 0/15 1/15 0/15 1/15
  • Lung: alveolar/bronchiolar adenoma 0/10 0/10 0/10 2/10
Non-Neoplastic Lesions
  • Liver: hepatocyte cytoplasmic vacuolization; increased severity of hepatocyte cytoplasmic vacuolization
  • Liver: hepatocyte cytoplasmic vacuolization; increased severity of hepatocyte cytoplasmic vacuolization
  • Liver: hepatocyte cytoplasmic vacuolization; increased severity of hepatocyte cytoplasmic vacuolization
  • Liver: hepatocyte cytoplasmic vacuolization; increased severity of hepatocyte cytoplasmic vacuolization

Levels of evidence information for Carcinogenesis and Genetic Toxicology Studies in p53 Haploinsufficient Mice in the Drinking Water Studies of Dichloroacetic Acid
  Male p53 Haploinsufficient Mice Female p53 Haploinsufficient Mice
  26 Weeks 41 Weeks 26 Weeks 41 Weeks
Levels of Evidence No Evidence No Evidence No Evidence No Evidence
Neoplastic Lesions None None None None
Non-Neoplastic Lesions
  • Liver: hepatocyte cytoplasmic vacuolization; increased severity of hepatocyte cytoplasmic vacuolization
  • Liver: hepatocyte cytoplasmic vacuolization; increased severity of hepatocyte cytoplasmic vacuolization
  • Liver: hepatocyte cytoplasmic vacuolization; increased severity of hepatocyte cytoplasmic vacuolization
  • Liver: hepatocyte cytoplasmic vacuolization; increased severity of hepatocyte cytoplasmic vacuolization
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.