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Table 1:
Methylene chloride-induced tumor incidence in Sprague-Dawley rats.
Dose Cervical/salivary gland region Benign mammary tumors
(ppm) sarcomas in male rats Males
Females
0 1/93 (1%) 7/95 (7%) 79/96 (82%)
500 0/94 3/95 (3%) 81/95 (85%)
1500 5/91 (5.5%) 7/95 (7%) 80/96 (83%)
3500 11/88 (12.5) * 14/95 (15%) 83/97 (86%)
HLC 1 0-2% 10% 80%
1 historical laboratory control
*
p < 0.05, Fisher’s exact probability test
In another inhalation study at Dow (Nitschke et al., 1988a) 90 SD rats/sex were exposed to 0
(control), 50, 200, and 500 ppm methylene chloride, 6 hours/day, 5 days/week, for 20 (males) or 24
(females) months. Most of the animal husbandry conditions were similar to the previous rat study with
the exception that the animals were housed in conventional animal rooms overnight and during the
weekends instead of in the chamber rooms. Female rats kept in chambers 100% of the time were
reported to have higher incidence of mammary tumors than in conventional animal rooms (Nitschke et
al., 1988a). In this study there was a nonsignificant increase in the number of benign mammary tumors
per tumor bearing female rat. No other tumors were observed.
An inhalation study of Ela:Eng (Syr) Syrian hamsters (Burek et al., 1984) were performed under similar
experimental exposure conditions as the 1980 Dow SD rat study. In males, there were no exposurerelated
increases in mortality rates, although mortality was high at 24 months (82% in control, 85% in
the 3500 ppm exposed group ). In females, control animals had 100% mortality at 24 months which
was higher than any of the exposed groups (90.3% in the 3500 ppm exposed group). No exposurerelated
neoplasms or nonneoplastic lesions were observed.
The strongest evidence for the carcinogenicity of methylene chloride to rodents was provided by the
NTP inhalation bioassays (NTP, 1986; Mennear et al., 1988). Fifty F344 rats and B6C3F 1 mice of
both sexes/group were exposed to methylene chloride for 6 hours/day, 5 days/week for 102 weeks
(concentrations: 0, 1000, 2000, and 4000 ppm for rats; 0, 2000, and 4000 ppm for mice). Rats were
housed in cages in exposure chambers and remained in the chambers during nonexposure periods.
Under the conditions of the study, benign mammary tumors were induced in F344 rats, and the female
rats exhibited a dose-related response (p < 0.001) (Table 2). NTP interpreted the incidence of benign
mammary tumors in female rats as “clear evidence of carcinogenicity” and in male rats as “some
evidence of carcinogenicity”. An elevated incidence of leukemia was observed in the 2000 ppm and
4000 ppm exposed female rats but this was also observed in controls. NTP considered this to be
“equivocal”.
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