Formaldehyde production promoted by rat nasal cytochrome P-450-dependent monooxygenases with nasal decongestants, essences, solvents, air pollutants, nicotine, and cocaine as substrates
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), Vol. 67:2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
COCAINE
METABOLISM
DRUGS
EXHAUST GASES
NICOTINE
AIR POLLUTION
BIOSYNTHESIS
FORMALDEHYDE
INHALATION
NOSE
OXYGENASES
POLLUTANTS
RATS
ALDEHYDES
ALKALOIDS
AMINES
ANESTHETICS
ANIMALS
ANTIDEPRESSANTS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
AZOLES
BODY
BODY AREAS
CENTRAL NERVOUS SYSTEM AGENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
ENZYMES
FACE
FLUIDS
GASEOUS WASTES
GASES
HEAD
HETEROCYCLIC COMPOUNDS
INTAKE
MAMMALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
PARASYMPATHOLYTICS
PARASYMPATHOMIMETICS
POLLUTION
PSYCHOTROPIC DRUGS
PYRIDINES
PYRROLES
PYRROLIDINES
RESPIRATORY SYSTEM
RODENTS
SYNTHESIS
VERTEBRATES
WASTES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)