Environmental Engineering Reference
In-Depth Information
nasoturbinate or the maxilloturbinate of 1,4-dioxane-treated rats. These rats received 1% 1,4-diox-
ane (1500 mg/kg per day) in the drinking water for eight days, followed by a single gavage dose of
10, 100, or 1000 mg/kg 12 h prior to sacrii ce. Archived tissues from the NCI (1978) bioassay were
reexamined to determine the primary sites for tumor formation in the nasal cavity following chronic
exposure in rats. Histopathology and cell proliferation were determined for specii c sites in the nasal
cavity that were related to tumor formation. This evaluation was performed in rats that were exposed
to drinking water containing 1% 1,4-dioxane (1500 mg/kg per day) for two weeks.
1,4-Dioxane and its metabolite 1,4-dioxane-2-one did not affect in vitro DNA repair in primary
hepatocyte cultures (Goldsworthy et al., 1991). In vivo DNA repair was also unaffected by acute
gavage exposure or ingestion of 1,4-dioxane in the drinking water for a one- or two-week period.
Hepatocyte cell proliferation was not affected by acute gavage exposure, but was increased approxi-
mately twofold following drinking-water exposure for 1-2 weeks. A i ve-day drinking-water exposure
to 1% 1,4-dioxane (1500 mg/kg per day) did not increase the activity of palmitoyl CoA or the liver-to-
body-weight ratio, suggesting that peroxisome proliferation does not play a role in the hepatocarcino-
genesis of 1,4-dioxane. Nannelli et al. (2005) also reported a lack of hepatic palmitoyl CoA induction
following 10 days of exposure to 1.5% 1,4-dioxane in the drinking water (2100 mg/kg per day).
Treatment of rats with 1% (1500 mg/kg per day) 1,4-dioxane for eight days did not alter DNA
repair in nasal epithelial cells (Goldsworthy et al., 1991). The addition of a single gavage dose of up
to 1000 mg/kg 12 h prior to sacrii ce also did not induce DNA repair. Reexamination of tissue sec-
tions from the NCI (1978) bioassay suggested that the majority of nasal tumors were located in the
dorsal nasal septum or the nasoturbinate of the anterior portion of the dorsal meatus (Goldsworthy
et al., 1991). The location of these tumors is consistent with the possibility that inhalation of droplets
of drinking water may be responsible for nasal lesions observed following chronic exposure to
1,4-dioxane. No histopathological lesions were observed in nasal sections of rats exposed to drink-
ing water containing 1% 1,4-dioxane (1500 mg/kg per day) for two weeks, and no increase was
observed in cell proliferation at the sites of highest tumor formation in the nasal cavity.
Sweeney et al. (2008) performed a l uorescent dye experiment to determine whether drinking
water directly contacts nasal tissues under bioassay study conditions. Rats (i ve per group) were
exposed to drinking water containing 0 or 0.5% 1,4-dioxane along with a l uorescent dye tracer.
The animals were sacrii ced approximately 24 h after the start of exposure, and the nasal cavity
was examined by l uorescence microscopy. An additional animal was given two gavage doses of
water containing dye (30 min between doses) and was sacrii ced 5 h later, in order to evaluate the
potential for systemic delivery to nasal tissues. Fluorescent dye was readily detectable in the oral
and nasal cavities of rats following drinking-water exposure. The dye was observed in several sec-
tions of the anterior third of the nose of each rat (nasal vestibule, maxillary turbinates, and dorsal
nasoturbinates) and was occasionally detected in the ethmoid turbinate region and nasopharynx.
No l uorescence was detected in the nasal cavity of the rat that received a gavage exposure. These
results suggest that drinking water directly contacts nasal tissues under bioassay study conditions
and may be responsible for the nasal lesions and tumors observed following chronic exposure to
1,4-dioxane.
Female Sprague Dawley rats (3-9 per group) were given 0, 168, 840, 2550, or 4200 mg/kg 1,4-
dioxane by corn oil gavage in two doses at 21 and 4 h prior to sacrii ce (Kitchin and Brown, 1990).
DNA damage (single-strand breaks measured by alkaline elution), ornithine decarboxylase (ODC)
activity, reduced glutathione content, and CYP content were measured in the liver. Serum ALT
activity and liver histopathology were also evaluated. No changes were observed in hepatic reduced
glutathione content or ALT activity. Light microscopy revealed minimal to mild vacuolar degenera-
tion in the cytoplasm of hepatocytes from three of i ve rats from the 2550 mg/kg dose group. No
histopathological lesions were seen in any other dose group, including rats given the highest dose of
4200 mg/kg. 1,4-Dioxane caused 43% and 50% increases in DNA single-strand breaks at dose
levels of 2550 and 4200 mg/kg, respectively. CYP content was also increased at the two highest-
dose levels (25% and 66%, respectively). ODC activity was increased approximately two-, i ve-, and
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