The Toxicity of Dimethylamine in F-344 Rats and B6C3F1 Mice following a 1-Year Inhalation Exposure

Buckley, Lorrene A.; Morgan, Kevin T.; Swenberg, James A.; James, R. Arden; Hamm, Thomas E.; Barrow, Craig S.

doi:10.1093/toxsci/5.2.341

Cited by 20 publications

(40 citation statements)

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“…Further degenerative changes such as vacuolation, nuclear pyknosis, and frank necrosis of sensory cells results in an atrophic epithelium. when mice were exposed to dinethylamine (20) and rats to dimethylethylamine (unpublished data) there was complete loss of sensory cells, with only the basal and sustentacular cells remaining (Plates 2 and 3). After exposure to other chemicals including zinc oxide (unpublished data), 3-methylfuran (25), methyl bromide (27), diethylnitrosamine, dimethylnitrosamine (4), or 3FMP (unpublished data), complete desquamation of the olfactory epithelium occurs, with only basal cells remaining (Plate 4).…”

Section: Degenerationmentioning

confidence: 91%

“…A logical consequence of the destruction of sensory cells is atrophy of the nerve bundles in the lamina propria (Plate 5) and, indeed, this is seen after treatment with acetaldehyde (12), formaldehyde (41), and dimethylamine (20). However, 3FMP (35), 3-methylfuran (25), and 3-methylindole (34) cause complete necrosis of the olfactory epithelium and, yet, the nerve bundles are preserved.…”

Section: Degenerationmentioning

confidence: 99%

“…Changes common to many of these chemicals, as well as more specific responses, will be described in this paper. (25), and dimethylamine (20) are known to be metabolized.…”

Section: Introductionmentioning

confidence: 99%

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Nonneoplastic Changes in the Olfactory Epithelium. Experimental Studies

Gaskell¹

1990

Environmental Health Perspectives

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Interest in the olfactory mucosa has increased in recent years, since it has been shown to possess a considerable amount of cytochrome P-450-dependent monooxygenase activity and a wide variety of chemicals have been identified as olfactory toxins. Many chemicals induce lesions of a general nature in the olfactory mucosa, i.e., inflammation, degeneration, regeneration, and proliferation, whereas others cause more specific effects.Changes in the olfactory mucosa with reference to chemicals that initiate them are reviewed in this paper. Studies with 3-trifluoromethyl pyridine (3FMP) illustrate some of these general changes and show the importance of examining the olfactory mucosa at early time periods. The earliest damage seen by light microscopy was 6 hr after a single inhalation exposure to 3FMP, and by day 3, early regenerative changes were observed. Changes were seen by electron microscopy 30 min after an oral dose, and the primary site of toxicity appeared to be the Bowman's glands.Although atrophy of nerve bundles in the lamina propria would be the expected consequence of severe necrosis of the sensory cells, this is not always the case. Exposure to irritants such as acetaldehyde, formaldehyde, and dimethylamine results in nerve bundle atrophy, but with chemicals such as 3FMP, 3-methylindole, and 3-methylfuran-which are activated by mixed-function oxidases-the nerve bundles remain intact. Future work, including metabolism studies, will provide more information on the mode of action of these chemicals.

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Section: Degenerationmentioning

confidence: 91%

Section: Degenerationmentioning

confidence: 99%

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Nonneoplastic Changes in the Olfactory Epithelium. Experimental Studies

Gaskell¹

1990

Environmental Health Perspectives

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“…6, 2004 MURINE OLFACTORY RESPONSES TO ALACHLOR 721 gland hyperplasia and massive intracellular accumulation of an eosinophilic material (Figure 1). Such accumulations of eosinophilic material have previously been reported in response to advanced age and inhaled compounds (Buckley et al, 1985;Wolf et al, 1995;Genter and Ali, 1998), but not as a consequence of systemically administered compounds. These observations are consistent with previous findings that mice appear to be resistant to the olfactory mucosal carcinogenicity of alachlor (U.S. EPA, 1985), and extend previous observations to demonstrate that alachlor-related histological changes can develop.…”

Section: The Olfactory Mucosa Of Untreated Apcmentioning

confidence: 56%

Strain-Specific Effects of Alachlor on Murine Olfactory Mucosal Responses

2004

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Chloracetanilide herbicides are multisite carcinogens in rodents. Progression of alachlor-induced olfactory tumors in rats is accompanied by cytoplasmic accumulation and nuclear localization of β-catenin, suggesting activation of Wnt signaling. Female CD-1 mice were resistant to alachlorinduced olfactory carcinogenesis. The current studies were performed to determine whether Apc Min/+ mice, which have activated Wnt signaling due to mutation of the second allele of Apc, would be susceptible to alachlor olfactory carcinogenesis. Female and male Apc Min/+ mice, as well as Apc +/+ littermates received alachlor in the diet (260 mg/kg/d) for up to 3 months. Female A/J and C57BL/6J wild-type mice were also treated (for 10 and 14 months, respectively), as these strains vary in sensitivity to many respiratory tract insults. No olfactory mucosal tumors were observed in any of the mice, although alachlor-treated Apc Min/+ mice developed histological changes similar to those in alachlor-treated rats. Alachlor-treated A/J mice developed pronounced intracellular accumulation of amorphous eosinophilic material in the olfactory mucosa, foci of respiratory-like metaplasia, and hyperplasia of nasal mucus glands. A similar but less intense response was seen in C57BL/6J mice. Mice and rats had equivalent levels of the putative bioactivating enzyme (CYP2A) in olfactory mucosa, and mice had induced hepatic CYP3A and CYP2B enzymes with alachlor treatment, which may increase alachlor elimination. These studies extend previous observations by describing alachlor-induced olfactory mucosal changes in mice and suggest that hepatic metabolic enzyme induction may be responsible for resistance of mice to alachlor-induced olfactory carcinogenesis.

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“…An increase in the abundance of intracytoplasmic eosinophilic globules in the respiratory and olfactory epithelia was also observed at significantly high incidences in the groups exposed to CMP. The exact nature and chemical composition of this eosinophilic material has not yet been determined, but it is conceivable that these globules represent a proteinaceous material secreted and accumulated in these cells [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] . These findings might be closely related to the administration of CMP by the inhalation route.…”

Section: Discussionmentioning

confidence: 99%

Chronic Ihhalation Toxicity and Carcinogenicity Studies of 3-Chloro-2-methylpropene in BDF1 Mice.

Katagiri¹,

Takeuchi²,

Mine³

et al. 2000

INDUSTRIAL HEALTH

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Chronic toxicity and carcinogenicity studies of 3-chloro-2-methylpropene (CMP), which has been widely used as an insecticide and chemical intermediate, were carried out in BDF1 mice. CMP was administered to mice in groups of 50 male and 50 female mice by the inhalation route 5 days per week for 104 weeks at doses of 0, 50, 100 or 200 ppm. Male and female mice in the CMPexposed groups had decreased body weight but no noticeable clinical signs when compared with the control group. Dose-related increases in the incidences of gastric mucosal hyperplasia and squamous cell papilloma were observed in both sexes, and squamous cell carcinoma was observed in only one male mouse in the 100 ppm group. An increased incidence of Harderian gland adenoma in female mice was also recognized. In the nasal cavity, eosinophilic exudate associated with atrophy of olfactory epithelia, respiratory metaplasia of olfactory epithelia and olfactory gland, and eosinophilic changes in respiratory and olfactory epithelia were increased in both sexes.

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The Toxicity of Dimethylamine in F-344 Rats and B6C3F1 Mice following a 1-Year Inhalation Exposure

Cited by 20 publications

References 0 publications

Nonneoplastic Changes in the Olfactory Epithelium. Experimental Studies

Nonneoplastic Changes in the Olfactory Epithelium. Experimental Studies

Strain-Specific Effects of Alachlor on Murine Olfactory Mucosal Responses

Chronic Ihhalation Toxicity and Carcinogenicity Studies of 3-Chloro-2-methylpropene in BDF1 Mice.

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