Reference SummaryDunnick JK, Toxicology 2003 Feb 1;183(1-3):221-34
Title |
Carcinogenic potential of o-nitrotoluene and p-nitrotoluene. |
Authors |
Dunnick JK; Burka LT; Mahler J; Sills R |
Journal |
Toxicology |
Volume |
183 |
Issue |
1-3 |
Year |
2003 |
Pages |
221-34 |
Abstract |
The potential of o-nitrotoluene and p-nitrotoluene to cause cancer in mammalian species was studied in male and female F344/N rats and B6C3F1 mice. These chemicals are on the EPA list of high production chemicals and there is potential for human exposure (High Production Volume Chemical List (2000) http://oaspub.cpa.gov/opptintr/chemrtk/volchall.htm.). o-Nitrotoluene, administered in the feed for up to 2 years, caused clear evidence for cancer at multiple sites in rats and mice. Male rats, receiving o-nitrotoluene in the feed ( approximately 0, 25, 50, or 90 mg/kg per day), developed treatment-related mesotheliomas, subcutaneous skin neoplasms, mammary gland fibroadenomas, and liver neoplasms. By 2 years, mesotheliomas, skin, liver, mammary gland and liver tumors also occurred in 'stop-study' male rats that received o-nitrotoluene at 125 or 315 mg/kg per day for only the first 3 months of study. These 'stop-studies' showed that the critical events leading to tumor formation occurred after 3 months of dosing, and these events were irreversible and eventually led to cancer at multiple sites. o-Nitrotoluene given in the feed to female rats ( approximately 0, 30, 60, or 100 mg/kg per day) and to male and female mice ( approximately 0, 150, 320, or 700 mg/kg per day) also caused a carcinogenic response. In female rats, treatment-related subcutaneous skin neoplasms and mammary gland fibroadenomas occurred. Hemangiosarcomas and carcinomas of the large intestine (cecum) were seen in treated male and female mice. In contrast to o-nitrotoluene, p-nitrotoluene given in the feed over approximately the same exposure levels caused only equivocal evidence of carcinogenic activity in male rats (subcutaneous skin neoplasms); some evidence of carcinogenic activity in female rats (clitoral gland neoplasms); equivocal evidence of carcinogenic activity in male mice (lung neoplasms); and no evidence of carcinogenic activity in female mice. Differences in the o-nitrotoluene and p-nitrotoluene carcinogenic activity may be due to differences in the metabolism of the parent compound to carcinogenic metabolites. |
Links |
J:81076 – MGI References 12504353 – National Library of Medicine/PubMed |
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| (C57BL/6 x C3H)F1 | Blood vessel hemangiosarcoma |
|
(Unspecified organ) |
0 - 6.67 |
|
| (C57BL/6 x C3H)F1 | Blood vessel hemangiosarcoma |
|
(Unspecified organ) |
3.39 - 28.33 |
|
| (C57BL/6 x C3H)F1 | Blood vessel hemangiosarcoma |
|
(Unspecified organ) |
5.08 - 100 |
|
| (C57BL/6 x C3H)F1 | Blood vessel hemangiosarcoma |
|
Muscle - Striated - Skeletal |
observed |
|
| (C57BL/6 x C3H)F1 | Blood vessel hemangiosarcoma |
|
Muscle - Striated - Skeletal |
observed |
|
| (C57BL/6 x C3H)F1 | Blood vessel hemangiosarcoma |
|
Subcutis |
observed |
|
| (C57BL/6 x C3H)F1 | Blood vessel hemangiosarcoma |
|
Subcutis |
observed |
|
| (C57BL/6 x C3H)F1 | Blood vessel hemangiosarcoma |
|
Peritoneum - Mesentery |
observed |
|
| (C57BL/6 x C3H)F1 | Blood vessel hemangiosarcoma |
|
Peritoneum - Mesentery |
observed |
|
| (C57BL/6 x C3H)F1 | Intestine - Large Intestine - Cecum carcinoma |
|
Intestine - Large Intestine - Cecum |
0 |
|
| (C57BL/6 x C3H)F1 | Intestine - Large Intestine - Cecum carcinoma |
|
Intestine - Large Intestine - Cecum |
0 - 20 |
|
| (C57BL/6 x C3H)F1 | Intestine - Large Intestine - Cecum carcinoma |
|
Intestine - Large Intestine - Cecum |
1.69 - 15 |
|
| (C57BL/6 x C3H)F1 | Liver tumor |
|
Liver |
15.25 |
|
| (C57BL/6 x C3H)F1 | Liver tumor |
|
Liver |
15.25 - 66.1 |
|
| (C57BL/6 x C3H)F1 | (Unspecified organ) neoplasm |
|
(Unspecified organ) |
0 |
|
| (C57BL/6 x C3H)F1 | (Unspecified organ) neoplasm |
|
(Unspecified organ) |
observed |
|
| (C57BL/6 x C3H)F1 | (Unspecified organ) neoplasm |
|
(Unspecified organ) |
0 - observed |