Acute and genetic toxicity of 1-nitropyrene and its fate after single oral doses to rats
The mammalian acute and genetic toxicity of 1-nitropyrene (NP) was studied because this and other nitroarenes are highly mutagenic toward bacteria and have been identified in emissions from combustion processes. A suspension of NP did not cause observable signs of acute toxicity and was not lethal when administered to male and female rats at single oral doses as high as 5.0 g/kg. Histological examination of stomach, intestine, lung, heart, spleen, pancreas, adrenal, and kidney from rats euthanized at 4 and 14 d after treatment revealed no detectable differences from control rats. Urine and feces were collected for 4 d after treatment with 5.0 g/kg. About 70% of the dose was present in the feces as NP, and about 2% was present as the reduced metabolite 1-aminopyrene (AP). Sulfate and glucuronide conjugates of AP were present in small amounts (<1%) in the urine, showing that at least some of the dose was absorbed. Bone marrow cells from female rats given NP orally at 0.5, 1.5, and 5.0 g/kg showed a slight dose-related increase in the frequency of sister chromatid exchanges. Both NP and AP showed low mutagenicity in Chinese hamster ovary cells in vitro. Evidence of reductive metabolism of NP in rats raises concern about the potential exposure of humans to this compound. However, the weak in vivo and in vitro genetic toxicity of NP at high dose levels in mammalian systems suggests that the potential hazard may not be as high as predicted from bacterial mutagenicity data.
- Research Organization:
- Lovelace Inhalation Toxicology Research Inst., Albuquerque, NM
- DOE Contract Number:
- AC04-76EV01013
- OSTI ID:
- 6429272
- Journal Information:
- J. Toxicol. Environ. Health; (United States), Journal Name: J. Toxicol. Environ. Health; (United States) Vol. 10; ISSN JTEHD
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AROMATICS
BIOLOGICAL EFFECTS
BODY
BONE MARROW CELLS
CELL CULTURES
CHROMOSOMAL ABERRATIONS
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
DOSE-RESPONSE RELATIONSHIPS
FEMALE GENITALS
GENETIC EFFECTS
GONADS
HAMSTERS
HYDROCARBONS
MAMMALS
METABOLITES
MUTAGEN SCREENING
MUTATIONS
NITRO COMPOUNDS
ORAL ADMINISTRATION
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OVARIES
PYRENE
RATS
RODENTS
SCREENING
SISTER CHROMATID EXCHANGES
SOMATIC CELLS
TOXICITY
VERTEBRATES