Table 4.
Effect of route of exposure on the tumor nature by benzene in tested in the National Toxicology Program chronic rodent bioassays and those observed in short-term genetically modified bioassays.
| Sex | Route | Assay | Target tissue | Dosea | Responses | Resultb | Study |
|---|---|---|---|---|---|---|---|
| M | Gavage | 2-year | Zymbal gland | 0, 25, 50, 100 mg/kg | 0/43, 1/34, 4/40, 21/39 | + | NTP, 1986 |
| Lymphoma | 4/49, 9/48, 9/50, 15/49 | ||||||
| Lung | 10/49, 16/48, 19/50, 21/49 | ||||||
| Harderian gland | 0/49, 9/46, 13/49, 11/48 | ||||||
| Preputial gland | 0/21, 3/28, 18/29, 28/35 | ||||||
| F | Gavage | 2-year | Zymbal gland | 0, 25, 50, 100 mg/kg | 0/43, 0/32, 1/37, 3/31 | + | |
| Lymphoma | 5/49, 24/45, 24/50, 20/49 | ||||||
| Lung | 4/49, 5/42, 10/50, 13/49 | ||||||
| Ovary (mixed) | 0/47, 1/44, 12/49, 7/48 | ||||||
| Ovary (granulosa) | 1/47, 1/44, 6/49, 7/48 | ||||||
| Mammary (carcinoma) | 0/49, 2/45, 5/50, 10/49 | ||||||
| Mammary (carcinosarcoma) | 0/49, 0/45, 1/50, 4/49 | ||||||
| F | Topical | Tg.AC | Skin | 0, ≤400 μl/week | 77% in treated | + | Tennant et al., 1995 |
| M | 0, 300, 450 μl/week | 0/10, 0/10, 3/10 | ec | Holden et al., 1998 | |||
| F | 0/10, 1/10, 1/10 | ec | |||||
| F | 0, 400, 800, 1600 μl/week | 3/5, 7/10, 8/10, 10/10 | + | Spalding et al., 1999 | |||
| F | 0, 75, 150, 300, 450, 600, 750 μl/week | 0/19, 3/13, 3/14, 12/15, 14/14, 15/15, 15/15 | + | Tennant et al., 1999a | |||
| F | Leukemia (granulocytic) | 0, 450, 800 μl/week | 0/19, 4/14, 11/15 | + | Furst et al., 2000 | ||
| F | Gavage | Tg.AC | Forestomach | 0, 50, 100, 200 mg/kg | 15/20, 10/13, 19/19, 14/18 | − | Tennant et al., 1999a |
| M | Gavage | Trp53 | Sarcoma | 0, 100, 200 mg/kg | 0/29, 7/20, 16/39 | + | French et al., 2001a |
| Lymphoma | 0, 100, 200 mg/kg | 0/29, 1/20, 3/39 | ed | ||||
| Sarcoma | 100 mg/kg | 19/39 | + | Hulla et al., 2001 | |||
| M | Gavage | rasH2 | Lung | 0, 50, 100 mg/kg | not reported | + | Yamamoto et al., 1998a |
| F | Forestomach | ||||||
| M | Inhalation | Trp53 (C57BL/6) | Hematopoietic neoplasia (primarily lymphomas) | 0, 33, 100, 300 ppm | 9/24, 11/27, 9/25, 23/26, 6/24, 20/24, 24/24e | + | Kawasaki et al., 2009 |
| Trp53 (C3H/He) | 0, 100, 300 ppm | + |
a
Administered five times per week unless otherwise indicated.
b
+ positive; − negative; e equivocal.
c
In the report, male and female animals were pooled for the analysis. Reported as a positive response.
d
Not significantly increased but trend is consistent with increases seen by other investigators where benzene exposure occurred by inhalation (Boley et al., 2000).
e
Kawasaki et al. (2009) indicate that 25/24 (104.2%) of the mice developed hematopoietic neoplasia.