(VCCEP) Tier 1 Pilot Submission for BENZENE - Tera

Table 6.4: Summary of Subchronic Inhalation Toxicity
Effect NOAEL/LOAEL Study Comments
Mortality Rat LOAEL (M,F) =
200 ppm
Hematological
alterations
Oral
Mouse LOAEL (M) =
100 ppm
Mouse LOAEL (M, F)
= 300 ppm
Rat LOAEL (M) = 88
ppm
Rat LOAEL (F) = 300
ppm
Rat NOAEL (M, F) =
30 ppm
Mouse NOAEL (F) =
30 ppm
Mouse LOAEL (M) =
10 ppm
Mouse LOAEL (F) =
100 ppm
Mouse NOAEL (M) =
3.1 ppm
Benzene VCCEP Submission 85
March 2006
Maltoni et al.,
1983,1985
Rosenthal and
Snyder, 1987
Cronkite et al., 1989
Wolf et al., 1956
Ward et al., 1985
Baarson et al., 1984
Seidel et al., 1989
Li et al., 1992
In general, mortality in
subchronic studies is
secondary to the
hematotoxicity.
Due to depressed cell
immunity after tumor
cell inoculation, not
directly induced
mortality.
Subchronic oral studies have been conducted in both mice and rats over a dose range (NTP,
1986; Huff et al., 1989). In the NTP study, rats and mice were treated with 0, 18, 36, 71, 143,
286, and 429mg/kg/day (actual volume in corn oil; nominal concentrations were, 0, 25, 50, 100,
200, 400, and 600mg/kg) 5 days/week for 17 weeks. Five additional animals/sex/group were
administered 0, 143, and 429mg/kg/day for 60 days. Hematological analyses were performed
at 60 days and after 17 weeks; necropsies were performed on all rats, and spleens were
evaluated histopathologically. No compound-related deaths were observed in rats or mice.
Body-Weight Effects: In the rat, body-weight depression was observed at 143mg/kg and
higher (14%–22% decrease). In the mouse, body-weight depression was observed at
71 mg/kg/day and higher (4%–10% decrease).
Hematological Effects: In the rat, dose-related leukopenia was observed in both sexes.
Lymphoid depletion in spleen was seen in males and females at 143 and 429 mg/kg for 60
days, and at 429mg/kg for 120 days. Increased extramedullary hematopoiesis was seen in
males and females at 429mg/kg for 120 days. In mice, dose related leukopenia and
lymphocytopenia were seen in males at and above 36mg/kg, and in females at 286 and
429mg/kg.