Formaldehyde production promoted by rat nasal cytochrome P-450-dependent monooxygenases with nasal decongestants, essences, solvents, air pollutants, nicotine, and cocaine as substrates

Journal Article · Tue Feb 01 04:00:00 EST 1983 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(83)90225-9· OSTI ID:5761779

Dahl, A R; Hadley, W M

To identify compounds which might be metabolized to formaldehyde in the nasal cavity, 32 potential substrates for cytochrome P-450-dependent monooxygenases were screened with rat nasal and, for comparison, liver microsomes. Tested substrates included 6 nasal decongestants, cocaine, nicotine, 9 essences, 3 potential air pollutants, and 12 solvents. Each test substrate, with the possible exception of the air pollutants, contained one or more N-methyl, O-methyl, or S-methyl groups. Eighteen of the tested materials were metabolized to produce formaldehyde by nasal microsomes. Five substrates, namely, the solvents HMPA and dimethylaniline, cocaine, and the essences dimethyl anthranilate and p-methoxyacetophenone, were metabolized to produce formaldehyde at rates exceeding 1000 pmol/mg microsomal protein/min by nasal microsomes. Eight substrates, including four nasal decongestants, nicotine, and an extract of diesel exhaust particles, were metabolized to produce formaldehyde at rates of 200 to 1000 pmol/mg microsomal protein/min. Five other substrates were metabolized to formaldehyde at detectable rates. The results indicate that a variety of materials which often come in contact with the nasal mucosa can be metabolized to formaldehyde by nasal enzymes. The released formaldehyde may influence the irritancy of inhaled compounds and has been suggested to play a role in the tumorigenicity of some compounds.

• Research Organization: Inhalation Toxicology Research Institute, Albuquerque, New Mexico
• OSTI ID: 5761779
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 67:2; ISSN TXAPA
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AIR POLLUTION
ALDEHYDES
ALKALOIDS
AMINES
ANESTHETICS
ANIMALS
ANTIDEPRESSANTS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
AZOLES
BIOSYNTHESIS
BODY
BODY AREAS
CENTRAL NERVOUS SYSTEM AGENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
COCAINE
DRUGS
ENZYMES
EXHAUST GASES
FACE
FLUIDS
FORMALDEHYDE
GASEOUS WASTES
GASES
HEAD
HETEROCYCLIC COMPOUNDS
INHALATION
INTAKE
MAMMALS
METABOLISM
NICOTINE
NOSE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
OXYGENASES
PARASYMPATHOLYTICS
PARASYMPATHOMIMETICS
POLLUTANTS
POLLUTION
PSYCHOTROPIC DRUGS
PYRIDINES
PYRROLES
PYRROLIDINES
RATS
RESPIRATORY SYSTEM
RODENTS
SYNTHESIS
VERTEBRATES
WASTES