Epidemiologic Notes and Reports An Evaluation of the
Immunotoxic Potential of Isobutyl Nitrite
Initial epidemiologic studies indicated that the use of
inhalant
drugs, such as amyl nitrite, isobutyl nitrite (IBN), and butyl
nitrite, may be a risk factor for acquired immunodeficiency
syndrome
(AIDS) (1,2). Because the immunotoxic potential of these drugs was
unknown, CDC undertook an immunotoxicologic evaluation of one of
the
most commercially available inhalants--IBN.
Balb/c mice were exposed to IBN at vapor concentrations of 20,
50,
and 300 parts per million (ppm) for 6.5 hours a day, 5 days a week,
for 3, 7, 13, or 18 weeks. At selected intervals, mice exposed to
either 50 or 300 ppm of IBN were removed from the exposure chambers
and tested for immunocompetency by the following assays: 1)
antibody-producing cells were counted by localized hemolysis in gel
assay (Jerne Plaque Assay) (3) 4 days after the mice had been
immunized intraperitoneally with sheep erythrocytes; 2) radiometric
skin testing with PPD (purified protein derivative) was performed
21
days after immunization with Freund's complete adjuvant (4); 3) the
lymphocyte blast transformation (LBT) assay was performed by using
splenic lymphocytes stimulated at several concentrations of the
following mitogens: phytohemagglutinin, concanavalin A, pokeweed
mitogen, or lipopolysaccharide. Each assay was performed on at
least
10 (five male, five female) exposed animals and 10 control animals
each time, and, except for the skin testing, assays for each animal
were done in replicates of three (plaque assay) or four (LBT).
In addition to the immunocompetency testing, all animals were
weighed weekly; their spleens, thymuses, and livers were weighed at
necropsy, when hematologic measurements, including white-cell
counts,
red-cell counts, differential white-cell counts, and methemaglobin
levels, were also determined. Fifteen major organs were removed
and
processed for histologic and pathologic analysis.
None of the animals exposed to IBN showed any evidence of
immunotoxic reactions. Methemaglobinemia was noted in animals
exposed
to 300 ppm of IBN, and some evidence of thymic atrophy, possibly
stress-related, was found in this group. All detailed histologic
examinations have not been completed.
Reported by Immunology Section, Laboratory Investigations Br, Div
of
Respiratory Disease Studies; Chronic Toxicology Section,
Experimental
Toxicology Br, Div of Biomedical and Behavioral Sciences, National
Institute of Occupational Safety and Health; AIDS Activity and Div
of
Host Factors, Center for Infectious Diseases; Office of the
Director,
Center for Environmental Health, CDC.
Editorial Note
Editorial Note: Aliphatic nitrites, such as IBN, are commercially
available as room odorizers but are commonly used as inhalant
"street"
drugs. The results of the present study, as well as the occurrence
of
AIDS among populations not commonly using inhalant nitrites,
suggests
that these drugs are not responsible for the basic immune defects
characteristic of AIDS.
Although the data obtained in this study indicate that IBN was
not
immunotoxic for mice, these drugs do have toxic effects. They have
been shown to be mutagenic in vitro (5) and are highly flammable.
Reported side effects include: dizziness, headache, tachycardia,
syncope, hypotension, and increased intraocular pressure; nitrites
have also been associated with methemoglobinemia and, rarely,
sudden
death (6). Nitrite inhalants do not appear to be implicated as a
cause of the immunosuppression seen in AIDS, but their role as a
cofactor in some of the illnesses found in this syndrome has not
been
ruled out.
References
Goedert JJ, Neuland CY, Wallen WC, et al. Amyl nitrite may
alter
T lymphocytes in homosexual men. Lancet 1982;1:412-6.
Marmor M, Friedman-Kien AE, Laubenstein L, et al. Risk factors
for Kaposi's sarcoma in homosexual men. Lancet 1982;1:1083-7.
Luster MI, Dean JH, Moore JA. Evaluation of immune functions
in
toxicology. In: Hayes W, ed. Methods in toxicology. New
York:
Raven Press, 1982, pp 516-86.
Quinto I. Mutagenicity of alkylnitrites in the Salmonella
test.
Boll Soc Ital Biol Sper. 1980;56:816-20.
Bruckner JV, Peterson RG. Toxicology of aliphatic and aromatic
hydrocarbons. In: National Institute on Drug Abuse (research
monograph no. 15). In: Sharp CW, Brehm ML, eds. Review of
inhalants: euphoria to dysfunction. Washington, D.C.:
Government Printing Office, 1977;124-63.
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