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 |
Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
---|---|---|---|---|---|
Swiss | Forestomach tumor |
|
Forestomach |
0 |
|
Swiss | Forestomach tumor |
|
Forestomach |
0 - 1.92 |
|
Swiss | Kidney - Cortex adenoma |
|
Kidney - Cortex |
9.62 |
|
Swiss | Kidney - Renal tubule carcinoma |
|
Kidney - Renal tubule |
3.85 - 5.77 |
|
Swiss | Kidney - Renal tubule carcinoma |
|
Kidney - Renal tubule |
0 - 1.92 |
|
Swiss | Kidney - Renal tubule carcinoma | Kidney - Renal tubule |
0 |
||
Swiss | Kidney - Renal tubule carcinoma |
|
Kidney - Renal tubule |
0 |
|
Swiss | Kidney - Renal tubule carcinoma |
|
Kidney - Renal tubule |
0 |
|
Swiss | Kidney adenoma | Kidney |
0 - 1.92 |
||
Swiss | Kidney adenoma |
|
Kidney |
0 - 3.85 |
|
Swiss | Kidney adenoma |
|
Kidney |
13.46 |
|
Swiss | Kidney adenoma |
|
Kidney |
0 |
|
Swiss | Kidney adenoma |
|
Kidney |
0 - 1.92 |
|
Swiss | Kidney tumor |
|
Kidney |
0 - 3.85 |
|
Swiss | Kidney tumor |
|
Kidney |
0 - 17.31 |
|
Swiss | Kidney tumor | Kidney |
0 - 1.92 |
||
Swiss | Kidney tumor |
|
Kidney |
0 - 1.92 |
|
Swiss | Kidney tumor |
|
Kidney |
0 - 1.92 |
|
Swiss | Kidney tumor - benign | Kidney |
0 - 1.92 |
||
Swiss | Kidney tumor - benign |
|
Kidney |
0 - 3.85 |
|
Swiss | Kidney tumor - benign |
|
Kidney |
3.85 - 13.46 |
|
Swiss | Kidney tumor - benign |
|
Kidney |
0 |
|
Swiss | Kidney tumor - benign |
|
Kidney |
0 - 1.92 |
|
C57BL | Kidney tumor - benign |
|
Kidney |
0 |
|
C57BL | Kidney tumor - benign |
|
Kidney |
0 |
|
CBA | Kidney tumor - benign |
|
Kidney |
0 |
|
CBA | Kidney tumor - benign |
|
Kidney |
0 |
|
CF-1 | Kidney tumor - benign |
|
Kidney |
0 |
|
CF-1 | Kidney tumor - benign |
|
Kidney |
0 |
|
Swiss | Kidney tumor - benign |
|
Kidney |
1.92 |
|
Swiss | Kidney tumor - benign |
|
Kidney |
5.77 |
|
C57BL | Kidney tumor - malignant |
|
Kidney |
0 |
|
C57BL | Kidney tumor - malignant |
|
Kidney |
0 |
|
CBA | Kidney tumor - malignant |
|
Kidney |
0 |
|
CBA | Kidney tumor - malignant |
|
Kidney |
0 |
|
CF-1 | Kidney tumor - malignant |
|
Kidney |
3.85 |
|
CF-1 | Kidney tumor - malignant |
|
Kidney |
1.92 |
|
Swiss | Kidney tumor - malignant |
|
Kidney |
0 |
|
Swiss | Kidney tumor - malignant |
|
Kidney |
5.77 |
|
Swiss | Kidney tumor - malignant | Kidney |
0 |
||
Swiss | Kidney tumor - malignant |
|
Kidney |
0 |
|
Swiss | Kidney tumor - malignant |
|
Kidney |
17.31 |
|
Swiss | Leukocyte lymphoma |
|
Leukocyte |
5.77 - 26.92 |
|
Swiss | Leukocyte lymphoma |
|
Leukocyte |
5.77 - 15.38 |
|
Swiss | Leukocyte lymphoma | Leukocyte |
9.62 - 26.92 |
||
Swiss | Leukocyte lymphoma |
|
Leukocyte |
9.62 - 13.46 |
|
Swiss | Leukocyte lymphoma |
|
Leukocyte |
21.25 - 25 |
|
C57BL | Leukocyte lymphoma |
|
Leukocyte |
19.23 |
|
C57BL | Leukocyte lymphoma |
|
Leukocyte |
13.46 |
|
CBA | Leukocyte lymphoma |
|
Leukocyte |
3.85 |
|
CBA | Leukocyte lymphoma |
|
Leukocyte |
0 |
|
CF-1 | Leukocyte lymphoma |
|
Leukocyte |
11.54 |
|
CF-1 | Leukocyte lymphoma |
|
Leukocyte |
11.54 |
|
Swiss | Leukocyte lymphoma |
|
Leukocyte |
15.38 |
|
Swiss | Leukocyte lymphoma |
|
Leukocyte |
15.38 |
|
Swiss | Liver hepatoma |
|
Liver |
1.92 |
|
Swiss | Liver tumor |
|
Liver |
0 - 26.92 |
|
Swiss | Liver tumor |
|
Liver |
0 - 15.38 |
|
Swiss | Liver tumor | Liver |
5.77 - 19.23 |
||
Swiss | Liver tumor |
|
Liver |
9.62 - 23.08 |
|
Swiss | Liver tumor |
|
Liver |
25 - 26.92 |
|
C57BL | Liver tumor - benign |
|
Liver |
3.85 |
|
C57BL | Liver tumor - benign |
|
Liver |
0 |
|
CBA | Liver tumor - benign |
|
Liver |
67.31 |
|
CBA | Liver tumor - benign |
|
Liver |
55.77 |
|
CF-1 | Liver tumor - benign |
|
Liver |
7.69 |
|
CF-1 | Liver tumor - benign |
|
Liver |
9.62 |
|
Swiss | Liver tumor - benign |
|
Liver |
11.54 |
|
Swiss | Liver tumor - benign |
|
Liver |
17.31 |
|
Swiss | Liver tumor - benign | Liver |
7.69 |
||
Swiss | Liver tumor - benign |
|
Liver |
13.46 |
|
Swiss | Liver tumor - benign |
|
Liver |
13.46 |
|
C57BL | Liver tumor - malignant |
|
Liver |
0 |
|
C57BL | Liver tumor - malignant |
|
Liver |
0 |
|
CBA | Liver tumor - malignant |
|
Liver |
3.85 |
|
CBA | Liver tumor - malignant |
|
Liver |
0 |
|
CF-1 | Liver tumor - malignant |
|
Liver |
0 |
|
CF-1 | Liver tumor - malignant |
|
Liver |
0 |
|
Swiss | Liver tumor - malignant |
|
Liver |
1.92 |
|
Swiss | Liver tumor - malignant |
|
Liver |
0 |
|
Swiss | Liver tumor - malignant | Liver |
0 |
||
Swiss | Liver tumor - malignant |
|
Liver |
3.85 |
|
Swiss | Liver tumor - malignant |
|
Liver |
1.92 |
|
Swiss | Lung tumor |
|
Lung |
4.81 - 39.23 |
|
Swiss | Lung tumor |
|
Lung |
3.85 - 40.38 |
|
Swiss | Lung tumor | Lung |
42.31 - 46.15 |
||
Swiss | Lung tumor |
|
Lung |
34.62 - 57.69 |
|
Swiss | Lung tumor |
|
Lung |
36.54 - 38.46 |
|
C57BL | Lung tumor - benign |
|
Lung |
1.92 |
|
C57BL | Lung tumor - benign |
|
Lung |
5.77 |
|
CBA | Lung tumor - benign |
|
Lung |
19.23 |
|
CBA | Lung tumor - benign |
|
Lung |
9.62 |
|
CF-1 | Lung tumor - benign |
|
Lung |
13.46 |
|
CF-1 | Lung tumor - benign |
|
Lung |
17.31 |
|
Swiss | Lung tumor - benign |
|
Lung |
7.69 |
|
Swiss | Lung tumor - benign |
|
Lung |
11.54 |
|
Swiss | Lung tumor - benign | Lung |
5.77 |
||
Swiss | Lung tumor - benign |
|
Lung |
5.77 |
|
Swiss | Lung tumor - benign |
|
Lung |
3.85 |
|
C57BL | Lung tumor - locally invasive |
|
Lung |
1.92 |
|
C57BL | Lung tumor - locally invasive |
|
Lung |
1.92 |
|
CBA | Lung tumor - locally invasive |
|
Lung |
5.77 |
|
CBA | Lung tumor - locally invasive |
|
Lung |
5.77 |
|
CF-1 | Lung tumor - locally invasive |
|
Lung |
3.85 |
|
CF-1 | Lung tumor - locally invasive |
|
Lung |
1.92 |
|
Swiss | Lung tumor - locally invasive |
|
Lung |
0 |
|
Swiss | Lung tumor - locally invasive |
|
Lung |
1.92 |
|
Swiss | Lung tumor - locally invasive | Lung |
0.96 |
||
Swiss | Lung tumor - locally invasive |
|
Lung |
1.92 |
|
Swiss | Lung tumor - locally invasive |
|
Lung |
1.92 |
|
Swiss | Lung tumor - malignant | Lung |
0 - 15.38 |
||
Swiss | Lung tumor - malignant |
|
Lung |
0 - 10 |
|
Swiss | Lung tumor - malignant |
|
Lung |
0 - 9.62 |
|
Swiss | Lung tumor - malignant |
|
Lung |
9.62 - 11.54 |
|
Swiss | Lung tumor - malignant |
|
Lung |
5.77 - 13.46 |
|
C57BL | Lung tumor - malignant |
|
Lung |
0 |
|
C57BL | Lung tumor - malignant |
|
Lung |
0 |
|
CBA | Lung tumor - malignant |
|
Lung |
0 |
|
CBA | Lung tumor - malignant |
|
Lung |
0 |
|
CF-1 | Lung tumor - malignant |
|
Lung |
0 |
|
CF-1 | Lung tumor - malignant |
|
Lung |
3.85 |
|
Swiss | Lung tumor - malignant |
|
Lung |
1.92 |
|
Swiss | Lung tumor - malignant |
|
Lung |
0 |
|
Swiss | Mammary gland tumor |
|
Mammary gland |
0 - 3.85 |
|
Swiss | Mammary gland tumor |
|
Mammary gland |
0 - 3.85 |
|
Swiss | Ovary hepatoma | Ovary |
0.96 |
||
Swiss | Testis tumor |
|
Testis |
0 |
|
Swiss | Testis tumor |
|
Testis |
0 - 3.85 |
|
Swiss | (Unspecified organ) neoplasm |
|
(Unspecified organ) |
3.85 - 19.23 |
|
Swiss | (Unspecified organ) neoplasm |
|
(Unspecified organ) |
1.92 - 7.69 |
|
Swiss | (Unspecified organ) neoplasm | (Unspecified organ) |
2.88 - 32.69 |
||
Swiss | (Unspecified organ) neoplasm |
|
(Unspecified organ) |
11.54 - 15.38 |
|
Swiss | (Unspecified organ) neoplasm |
|
(Unspecified organ) |
9.62 |
|
C57BL | (Unspecified organ) neoplasm |
|
(Unspecified organ) |
3.85 |
|
C57BL | (Unspecified organ) neoplasm |
|
(Unspecified organ) |
1.92 |
|
CBA | (Unspecified organ) neoplasm |
|
(Unspecified organ) |
1.92 |
|
CBA | (Unspecified organ) neoplasm |
|
(Unspecified organ) |
1.92 |
|
CF-1 | (Unspecified organ) neoplasm |
|
(Unspecified organ) |
7.69 |
|
CF-1 | (Unspecified organ) neoplasm |
|
(Unspecified organ) |
7.69 |
|
Swiss | (Unspecified organ) neoplasm |
|
(Unspecified organ) |
11.54 |
|
Swiss | (Unspecified organ) neoplasm |
|
(Unspecified organ) |
1.92 |
|
Swiss | (Unspecified organ) tumor |
|
(Unspecified organ) |
19.23 - 75 |
|
Swiss | (Unspecified organ) tumor |
|
(Unspecified organ) |
19.23 - 57.69 |
|
Swiss | (Unspecified organ) tumor | (Unspecified organ) |
26.92 - 76.92 |
||
Swiss | (Unspecified organ) tumor |
|
(Unspecified organ) |
67.31 - 69.23 |
|
Swiss | (Unspecified organ) tumor |
|
(Unspecified organ) |
65.38 - 71.15 |
|
C57BL | (Unspecified organ) tumor |
|
(Unspecified organ) |
30.77 |
|
C57BL | (Unspecified organ) tumor |
|
(Unspecified organ) |
23.08 |
|
CBA | (Unspecified organ) tumor |
|
(Unspecified organ) |
80.77 |
|
CBA | (Unspecified organ) tumor |
|
(Unspecified organ) |
63.46 |
|
CF-1 | (Unspecified organ) tumor |
|
(Unspecified organ) |
30.77 |
|
CF-1 | (Unspecified organ) tumor |
|
(Unspecified organ) |
42.31 |
|
Swiss | (Unspecified organ) tumor |
|
(Unspecified organ) |
46.15 |
|
Swiss | (Unspecified organ) tumor |
|
(Unspecified organ) |
38.46 |
|
Swiss | (Unspecified organ) tumor - malignant |
|
(Unspecified organ) |
7.69 - 53.85 |
|
Swiss | (Unspecified organ) tumor - malignant |
|
(Unspecified organ) |
13.46 - 28.85 |
|
Swiss | (Unspecified organ) tumor - malignant | (Unspecified organ) |
11.54 - 50 |
||
Swiss | (Unspecified organ) tumor - malignant |
|
(Unspecified organ) |
21.15 - 34.62 |
|
Swiss | (Unspecified organ) tumor - malignant |
|
(Unspecified organ) |
32.69 - 38.46 |
|
C57BL | (Unspecified organ) tumor - malignant |
|
(Unspecified organ) |
23.08 |
|
C57BL | (Unspecified organ) tumor - malignant |
|
(Unspecified organ) |
15.38 |
|
CBA | (Unspecified organ) tumor - malignant |
|
(Unspecified organ) |
7.69 |
|
CBA | (Unspecified organ) tumor - malignant |
|
(Unspecified organ) |
1.92 |
|
CF-1 | (Unspecified organ) tumor - malignant |
|
(Unspecified organ) |
21.15 |
|
CF-1 | (Unspecified organ) tumor - malignant |
|
(Unspecified organ) |
23.08 |
|
Swiss | (Unspecified organ) tumor - malignant |
|
(Unspecified organ) |
46.15 |
|
Swiss | (Unspecified organ) tumor - malignant |
|
(Unspecified organ) |
30.77 |