home edit2 whole TSD November 2002 PDF format - OEHHA

Table 2:
Methylene chloride-induced benign mammary tumors incidence in F344/N rats.
Dose (ppm)
Benign mammary tumors
males 1 female 2
0 1/50 (2%) 5/50 (10%)
1000 1/50 (2%) 11/50 (22%)
2000 4/50 (8%) 13/50 (26%)
4000 9/50 (18%) * 23/50 (46%) *
Historical Control
(Fibroadenoma)
a. Laboratory
0% 16%
b. NTP
3% 28%
1
Fibroadenoma, adenoma, or fibroma.
2
Fibroadenoma or adenoma.
* (p < 0.001), Fisher exact test.
In B6C3F 1 mice, exposure to methylene chloride by inhalation (NTP, 1986; Mennear et al., 1988) was
associated with an increased incidence and multiplicity of alveolar and bronchiolar tumors (adenoma and
carcinoma) in the lungs of both sexes. The incidence and multiplicity of liver tumors were also increased
in both sexes. Male mice had an increased incidence of hepatocellular carcinomas and of adenomas or
carcinomas (combined) at the high exposure level, while female mice had dose-related increases in
hepatocellular adenoma and hepatocellular carcinoma (Table 3). The survival in both male and female
high dose groups was significantly (p < 0.001, trend test) decreased as compared to controls.
Table 3: Methylene chloride-induced neoplasms incidence in B6C3F 1 mice
Dose (ppm) Alveolar /Bronchiolar Adenomas(A) or
Carcinomas(C) or combined
Male
Female
0 A: 3/50(6%) 2/50(4%)
C: 2/50(4%) 1/50(2%)
A, C 5/50(10%) 3/50(6%)
2000 A: 19/50(38%)* 23/48(48%)*
C: 10/50(20%) 13/48(27%)*
A, C 27/50(54%)* 30/48(63%)*
4000 A: 24/50 (48%)* 28/48(58%)*
C: 28/50(56%) * 29/48(60%)*
A, C 40/50(80%)* 41/48(85%)*
Historical control
a. Laboratory
A: -- --
C: -- --
A, C 31% 10%
b. NTP A: -- --
C: -- --
A, C 17% 7%
* Fisher Exact Test (p < 0.001).
Hepatocellular Adenomas or
Carcinomas or combined
Male
Female
10/50(20%) 2/50(4%)
13/50(26%) 1/50(2%)
22/50(44%) 3/50(6%)
14/49(29%) 6/48(13%)
15/49(31%) 11/48(23%)*
24/49(49%) 16/48(33%) *
14/49(29%) 22/48(46%)
26/49(53%) 32/48(67%)*
33/49(67%) 40/48(83%)*
13% 1%
15% 4%
28% 5%
10% 4%
21% 5%
30% 8%
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