Reference SummaryRoe FJ, J Environ Pathol Toxicol 1979 Jan-Feb;2(3):799-819

Title

 Safety evaluation of toothpaste containing chloroform. I. Long-term studies in mice.

Authors

 Roe FJ; Palmer AK; Worden AN; Van Abbe NJ

Journal

 J Environ Pathol Toxicol

Volume

 2

Issue

 3

Year

 1979

Pages

 799-819

Abstract

 In three experiments, chloroform was administered to mice by gavage in a toothpaste base or in arachis oil, in doses up to 60 mg/kg/d on 6 days/wk for 8 wks. Control groups were left untreated or given vehicle only. In general, there were more survivors in chloroform-treated groups than in the controls. In the case of the males of three strains (C57BL, CBA and CF/1), treatment was associated with no adverse affect on the incidence of any type of neoplasm or any other parameter. In the males but not the females of a fourth strain (ICI) and in doses of 60 mg/kg/d but not of 17 mg/kg/d, exposure to chloroform in toothpaste base as a vehicle was associated with increased incidence of epithelial tumours of the kidney. A more pronounced effect of the same kind was seen in mice given 60 mg CHCl3/kg/d in an archis oil vehicle. This treatment was also associated with a higher incidence and severity of non-neoplastic renal disease. The mechanisms underlying the peculiar strain- and sex-specific susceptibility of ICI male mice to develop renal tumours when exposed to chloroform remain obcure; spontaneous renal tumours were also seen in vehicle control mice and possible ways in which this tendency may be enhanced by chloroform treatment are discussed. At the dose levels tested, namely 113 and 400 times average human exposure levels from the use of toothpaste (with 3.5 percent chloroform content), no adverse affect was seen in the liver and there was no increased incidence of liver tumours even in the higher liver tumour susceptible CBA strain. At the 17 mg CHCl3/kg/d level, equivalent to 113 times average human exposure from toothpaste use, no excess of renal tumours was seen even in males of the peculiarly susceptible ICI strain.

Links

 J:101462 – MGI References
422936 – National Library of Medicine/PubMed

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
Swiss Forestomach tumor
  • toothpaste (control)
 Forestomach

0
Swiss Forestomach tumor
  • chloroform
  • toothpaste (control)
 Forestomach

0 - 1.92
Swiss Kidney - Cortex adenoma
  • chloroform
  • toothpaste (control)
 Kidney - Cortex

9.62
Swiss Kidney - Renal tubule carcinoma
  • chloroform
  • toothpaste (control)
 Kidney - Renal tubule

3.85 - 5.77
Swiss Kidney - Renal tubule carcinoma
  • chloroform
  • eucalyptol
  • toothpaste (control)
 Kidney - Renal tubule

0 - 1.92
Swiss Kidney - Renal tubule carcinoma Kidney - Renal tubule

0
Swiss Kidney - Renal tubule carcinoma
  • toothpaste (control)
 Kidney - Renal tubule

0
Swiss Kidney - Renal tubule carcinoma
  • chloroform
  • peppermint
  • toothpaste (control)
 Kidney - Renal tubule

0
Swiss Kidney adenoma Kidney

0 - 1.92
Swiss Kidney adenoma
  • toothpaste (control)
 Kidney

0 - 3.85
Swiss Kidney adenoma
  • chloroform
  • toothpaste (control)
 Kidney

13.46
Swiss Kidney adenoma
  • chloroform
  • eucalyptol
  • toothpaste (control)
 Kidney

0
Swiss Kidney adenoma
  • chloroform
  • peppermint
  • toothpaste (control)
 Kidney

0 - 1.92
Swiss Kidney tumor
  • toothpaste (control)
 Kidney

0 - 3.85
Swiss Kidney tumor
  • chloroform
  • toothpaste (control)
 Kidney

0 - 17.31
Swiss Kidney tumor Kidney

0 - 1.92
Swiss Kidney tumor
  • chloroform
  • eucalyptol
  • toothpaste (control)
 Kidney

0 - 1.92
Swiss Kidney tumor
  • chloroform
  • peppermint
  • toothpaste (control)
 Kidney

0 - 1.92
Swiss Kidney tumor - benign Kidney

0 - 1.92
Swiss Kidney tumor - benign
  • toothpaste (control)
 Kidney

0 - 3.85
Swiss Kidney tumor - benign
  • chloroform
  • toothpaste (control)
 Kidney

3.85 - 13.46
Swiss Kidney tumor - benign
  • chloroform
  • eucalyptol
  • toothpaste (control)
 Kidney

0
Swiss Kidney tumor - benign
  • chloroform
  • peppermint
  • toothpaste (control)
 Kidney

0 - 1.92
C57BL Kidney tumor - benign
  • toothpaste (control)
 Kidney

0
C57BL Kidney tumor - benign
  • chloroform
  • toothpaste (control)
 Kidney

0
CBA Kidney tumor - benign
  • toothpaste (control)
 Kidney

0
CBA Kidney tumor - benign
  • chloroform
  • toothpaste (control)
 Kidney

0
CF-1 Kidney tumor - benign
  • toothpaste (control)
 Kidney

0
CF-1 Kidney tumor - benign
  • chloroform
  • toothpaste (control)
 Kidney

0
Swiss Kidney tumor - benign
  • Arachis Oil
 Kidney

1.92
Swiss Kidney tumor - benign
  • Arachis Oil
  • chloroform
 Kidney

5.77
C57BL Kidney tumor - malignant
  • toothpaste (control)
 Kidney

0
C57BL Kidney tumor - malignant
  • chloroform
  • toothpaste (control)
 Kidney

0
CBA Kidney tumor - malignant
  • toothpaste (control)
 Kidney

0
CBA Kidney tumor - malignant
  • chloroform
  • toothpaste (control)
 Kidney

0
CF-1 Kidney tumor - malignant
  • toothpaste (control)
 Kidney

3.85
CF-1 Kidney tumor - malignant
  • chloroform
  • toothpaste (control)
 Kidney

1.92
Swiss Kidney tumor - malignant
  • toothpaste (control)
 Kidney

0
Swiss Kidney tumor - malignant
  • chloroform
  • toothpaste (control)
 Kidney

5.77
Swiss Kidney tumor - malignant Kidney

0
Swiss Kidney tumor - malignant
  • Arachis Oil
 Kidney

0
Swiss Kidney tumor - malignant
  • Arachis Oil
  • chloroform
 Kidney

17.31
Swiss Leukocyte lymphoma
  • toothpaste (control)
 Leukocyte

5.77 - 26.92
Swiss Leukocyte lymphoma
  • chloroform
  • toothpaste (control)
 Leukocyte

5.77 - 15.38
Swiss Leukocyte lymphoma Leukocyte

9.62 - 26.92
Swiss Leukocyte lymphoma
  • chloroform
  • eucalyptol
  • toothpaste (control)
 Leukocyte

9.62 - 13.46
Swiss Leukocyte lymphoma
  • chloroform
  • peppermint
  • toothpaste (control)
 Leukocyte

21.25 - 25
C57BL Leukocyte lymphoma
  • toothpaste (control)
 Leukocyte

19.23
C57BL Leukocyte lymphoma
  • chloroform
  • toothpaste (control)
 Leukocyte

13.46
CBA Leukocyte lymphoma
  • toothpaste (control)
 Leukocyte

3.85
CBA Leukocyte lymphoma
  • chloroform
  • toothpaste (control)
 Leukocyte

0
CF-1 Leukocyte lymphoma
  • toothpaste (control)
 Leukocyte

11.54
CF-1 Leukocyte lymphoma
  • chloroform
  • toothpaste (control)
 Leukocyte

11.54
Swiss Leukocyte lymphoma
  • Arachis Oil
 Leukocyte

15.38
Swiss Leukocyte lymphoma
  • Arachis Oil
  • chloroform
 Leukocyte

15.38
Swiss Liver hepatoma
  • chloroform
 Liver

1.92
Swiss Liver tumor
  • toothpaste (control)
 Liver

0 - 26.92
Swiss Liver tumor
  • chloroform
  • toothpaste (control)
 Liver

0 - 15.38
Swiss Liver tumor Liver

5.77 - 19.23
Swiss Liver tumor
  • chloroform
  • eucalyptol
  • toothpaste (control)
 Liver

9.62 - 23.08
Swiss Liver tumor
  • chloroform
  • peppermint
  • toothpaste (control)
 Liver

25 - 26.92
C57BL Liver tumor - benign
  • toothpaste (control)
 Liver

3.85
C57BL Liver tumor - benign
  • chloroform
  • toothpaste (control)
 Liver

0
CBA Liver tumor - benign
  • toothpaste (control)
 Liver

67.31
CBA Liver tumor - benign
  • chloroform
  • toothpaste (control)
 Liver

55.77
CF-1 Liver tumor - benign
  • toothpaste (control)
 Liver

7.69
CF-1 Liver tumor - benign
  • chloroform
  • toothpaste (control)
 Liver

9.62
Swiss Liver tumor - benign
  • toothpaste (control)
 Liver

11.54
Swiss Liver tumor - benign
  • chloroform
  • toothpaste (control)
 Liver

17.31
Swiss Liver tumor - benign Liver

7.69
Swiss Liver tumor - benign
  • Arachis Oil
 Liver

13.46
Swiss Liver tumor - benign
  • Arachis Oil
  • chloroform
 Liver

13.46
C57BL Liver tumor - malignant
  • toothpaste (control)
 Liver

0
C57BL Liver tumor - malignant
  • chloroform
  • toothpaste (control)
 Liver

0
CBA Liver tumor - malignant
  • toothpaste (control)
 Liver

3.85
CBA Liver tumor - malignant
  • chloroform
  • toothpaste (control)
 Liver

0
CF-1 Liver tumor - malignant
  • toothpaste (control)
 Liver

0
CF-1 Liver tumor - malignant
  • chloroform
  • toothpaste (control)
 Liver

0
Swiss Liver tumor - malignant
  • toothpaste (control)
 Liver

1.92
Swiss Liver tumor - malignant
  • chloroform
  • toothpaste (control)
 Liver

0
Swiss Liver tumor - malignant Liver

0
Swiss Liver tumor - malignant
  • Arachis Oil
 Liver

3.85
Swiss Liver tumor - malignant
  • Arachis Oil
  • chloroform
 Liver

1.92
Swiss Lung tumor
  • toothpaste (control)
 Lung

4.81 - 39.23
Swiss Lung tumor
  • chloroform
  • toothpaste (control)
 Lung

3.85 - 40.38
Swiss Lung tumor Lung

42.31 - 46.15
Swiss Lung tumor
  • chloroform
  • eucalyptol
  • toothpaste (control)
 Lung

34.62 - 57.69
Swiss Lung tumor
  • chloroform
  • peppermint
  • toothpaste (control)
 Lung

36.54 - 38.46
C57BL Lung tumor - benign
  • toothpaste (control)
 Lung

1.92
C57BL Lung tumor - benign
  • chloroform
  • toothpaste (control)
 Lung

5.77
CBA Lung tumor - benign
  • toothpaste (control)
 Lung

19.23
CBA Lung tumor - benign
  • chloroform
  • toothpaste (control)
 Lung

9.62
CF-1 Lung tumor - benign
  • toothpaste (control)
 Lung

13.46
CF-1 Lung tumor - benign
  • chloroform
  • toothpaste (control)
 Lung

17.31
Swiss Lung tumor - benign
  • toothpaste (control)
 Lung

7.69
Swiss Lung tumor - benign
  • chloroform
  • toothpaste (control)
 Lung

11.54
Swiss Lung tumor - benign Lung

5.77
Swiss Lung tumor - benign
  • Arachis Oil
 Lung

5.77
Swiss Lung tumor - benign
  • Arachis Oil
  • chloroform
 Lung

3.85
C57BL Lung tumor - locally invasive
  • toothpaste (control)
 Lung

1.92
C57BL Lung tumor - locally invasive
  • chloroform
  • toothpaste (control)
 Lung

1.92
CBA Lung tumor - locally invasive
  • toothpaste (control)
 Lung

5.77
CBA Lung tumor - locally invasive
  • chloroform
  • toothpaste (control)
 Lung

5.77
CF-1 Lung tumor - locally invasive
  • toothpaste (control)
 Lung

3.85
CF-1 Lung tumor - locally invasive
  • chloroform
  • toothpaste (control)
 Lung

1.92
Swiss Lung tumor - locally invasive
  • toothpaste (control)
 Lung

0
Swiss Lung tumor - locally invasive
  • chloroform
  • toothpaste (control)
 Lung

1.92
Swiss Lung tumor - locally invasive Lung

0.96
Swiss Lung tumor - locally invasive
  • Arachis Oil
 Lung

1.92
Swiss Lung tumor - locally invasive
  • Arachis Oil
  • chloroform
 Lung

1.92
Swiss Lung tumor - malignant Lung

0 - 15.38
Swiss Lung tumor - malignant
  • toothpaste (control)
 Lung

0 - 10
Swiss Lung tumor - malignant
  • chloroform
  • toothpaste (control)
 Lung

0 - 9.62
Swiss Lung tumor - malignant
  • chloroform
  • eucalyptol
  • toothpaste (control)
 Lung

9.62 - 11.54
Swiss Lung tumor - malignant
  • chloroform
  • peppermint
  • toothpaste (control)
 Lung

5.77 - 13.46
C57BL Lung tumor - malignant
  • toothpaste (control)
 Lung

0
C57BL Lung tumor - malignant
  • chloroform
  • toothpaste (control)
 Lung

0
CBA Lung tumor - malignant
  • toothpaste (control)
 Lung

0
CBA Lung tumor - malignant
  • chloroform
  • toothpaste (control)
 Lung

0
CF-1 Lung tumor - malignant
  • toothpaste (control)
 Lung

0
CF-1 Lung tumor - malignant
  • chloroform
  • toothpaste (control)
 Lung

3.85
Swiss Lung tumor - malignant
  • Arachis Oil
 Lung

1.92
Swiss Lung tumor - malignant
  • Arachis Oil
  • chloroform
 Lung

0
Swiss Mammary gland tumor
  • toothpaste (control)
 Mammary gland

0 - 3.85
Swiss Mammary gland tumor
  • chloroform
  • toothpaste (control)
 Mammary gland

0 - 3.85
Swiss Ovary hepatoma Ovary

0.96
Swiss Testis tumor
  • toothpaste (control)
 Testis

0
Swiss Testis tumor
  • chloroform
  • toothpaste (control)
 Testis

0 - 3.85
Swiss (Unspecified organ) neoplasm
  • toothpaste (control)
 (Unspecified organ)

3.85 - 19.23
Swiss (Unspecified organ) neoplasm
  • chloroform
  • toothpaste (control)
 (Unspecified organ)

1.92 - 7.69
Swiss (Unspecified organ) neoplasm (Unspecified organ)

2.88 - 32.69
Swiss (Unspecified organ) neoplasm
  • chloroform
  • eucalyptol
  • toothpaste (control)
 (Unspecified organ)

11.54 - 15.38
Swiss (Unspecified organ) neoplasm
  • chloroform
  • peppermint
  • toothpaste (control)
 (Unspecified organ)

9.62
C57BL (Unspecified organ) neoplasm
  • toothpaste (control)
 (Unspecified organ)

3.85
C57BL (Unspecified organ) neoplasm
  • chloroform
  • toothpaste (control)
 (Unspecified organ)

1.92
CBA (Unspecified organ) neoplasm
  • toothpaste (control)
 (Unspecified organ)

1.92
CBA (Unspecified organ) neoplasm
  • chloroform
  • toothpaste (control)
 (Unspecified organ)

1.92
CF-1 (Unspecified organ) neoplasm
  • toothpaste (control)
 (Unspecified organ)

7.69
CF-1 (Unspecified organ) neoplasm
  • chloroform
  • toothpaste (control)
 (Unspecified organ)

7.69
Swiss (Unspecified organ) neoplasm
  • Arachis Oil
 (Unspecified organ)

11.54
Swiss (Unspecified organ) neoplasm
  • Arachis Oil
  • chloroform
 (Unspecified organ)

1.92
Swiss (Unspecified organ) tumor
  • toothpaste (control)
 (Unspecified organ)

19.23 - 75
Swiss (Unspecified organ) tumor
  • chloroform
  • toothpaste (control)
 (Unspecified organ)

19.23 - 57.69
Swiss (Unspecified organ) tumor (Unspecified organ)

26.92 - 76.92
Swiss (Unspecified organ) tumor
  • chloroform
  • eucalyptol
  • toothpaste (control)
 (Unspecified organ)

67.31 - 69.23
Swiss (Unspecified organ) tumor
  • chloroform
  • peppermint
  • toothpaste (control)
 (Unspecified organ)

65.38 - 71.15
C57BL (Unspecified organ) tumor
  • toothpaste (control)
 (Unspecified organ)

30.77
C57BL (Unspecified organ) tumor
  • chloroform
  • toothpaste (control)
 (Unspecified organ)

23.08
CBA (Unspecified organ) tumor
  • toothpaste (control)
 (Unspecified organ)

80.77
CBA (Unspecified organ) tumor
  • chloroform
  • toothpaste (control)
 (Unspecified organ)

63.46
CF-1 (Unspecified organ) tumor
  • toothpaste (control)
 (Unspecified organ)

30.77
CF-1 (Unspecified organ) tumor
  • chloroform
  • toothpaste (control)
 (Unspecified organ)

42.31
Swiss (Unspecified organ) tumor
  • Arachis Oil
 (Unspecified organ)

46.15
Swiss (Unspecified organ) tumor
  • Arachis Oil
  • chloroform
 (Unspecified organ)

38.46
Swiss (Unspecified organ) tumor - malignant
  • toothpaste (control)
 (Unspecified organ)

7.69 - 53.85
Swiss (Unspecified organ) tumor - malignant
  • chloroform
  • toothpaste (control)
 (Unspecified organ)

13.46 - 28.85
Swiss (Unspecified organ) tumor - malignant (Unspecified organ)

11.54 - 50
Swiss (Unspecified organ) tumor - malignant
  • chloroform
  • eucalyptol
  • toothpaste (control)
 (Unspecified organ)

21.15 - 34.62
Swiss (Unspecified organ) tumor - malignant
  • chloroform
  • peppermint
  • toothpaste (control)
 (Unspecified organ)

32.69 - 38.46
C57BL (Unspecified organ) tumor - malignant
  • toothpaste (control)
 (Unspecified organ)

23.08
C57BL (Unspecified organ) tumor - malignant
  • chloroform
  • toothpaste (control)
 (Unspecified organ)

15.38
CBA (Unspecified organ) tumor - malignant
  • toothpaste (control)
 (Unspecified organ)

7.69
CBA (Unspecified organ) tumor - malignant
  • chloroform
  • toothpaste (control)
 (Unspecified organ)

1.92
CF-1 (Unspecified organ) tumor - malignant
  • toothpaste (control)
 (Unspecified organ)

21.15
CF-1 (Unspecified organ) tumor - malignant
  • chloroform
  • toothpaste (control)
 (Unspecified organ)

23.08
Swiss (Unspecified organ) tumor - malignant
  • Arachis Oil
 (Unspecified organ)

46.15
Swiss (Unspecified organ) tumor - malignant
  • Arachis Oil
  • chloroform
 (Unspecified organ)

30.77