Biomonitoring Summary

Nitrobenzene

CAS No. 98-95-3

General Information

Nitrobenzene is a synthetic aromatic chemical made from benzene and used to manufacture aniline, which is in turn, is used to make some types of polyurethanes. Nitrobenzene is also used in the synthesis of other chemicals, including pesticides, dyes, and explosives and as a solvent in petroleum refining. Less common or discontinued applications include use in shoe polish, special lubricating oils, and as an almond flavoring. Environmental sources for nitrobenzene include emissions from its production or use and the atmospheric chemical reaction of benzene with nitrogen oxides. Nitrobenzene was detected infrequently at low levels in ambient air taken in urban, rural and waste disposal areas in the 1970s and 1980s (IPCS, 2003). Nitrobenzene was rarely detected in surface and industrial effluent water and was not detected in soil and sediment specimens obtained from selected locations in the United States (IPCS, 2003).

The general population can be exposed infrequently to nitrobenzene in contaminated air and water. Workers may be exposed to nitrobenzene during its use or production. Nitrobenzene is absorbed after dermal, inhalational, or oral exposure and then metabolized to various intermediates. About 10 to 20 percent of a dose is eliminated in the urine as p-nitrophenol, which is used in biological monitoring of occupational exposures. A smaller fraction of a dose is eliminated in urine as p-aminophenol (Astier, 1992; IARC, 1996). The nitroreduced metabolites of nitrobenzene may mediate some toxic effects (e.g., methemoglobinemia or carcinogenicity) (IPCS, 2003).

Human health effects from nitrobenzene at low environmental doses or at biomonitored levels from low environmental exposures are unknown. People having accidental exposures to large amounts of nitrobenzene have developed methemoglobinemia, hemolytic anemia, and toxic hepatitis (IARC, 1996). In animals treated with high doses of nitrobenzene, methemoglobinemia, testicular atrophy and reduced sperm counts, and increased liver and kidney weights were observed (NTP, 2002). In animals exposed to high concentrations of nitrobenzene in air, multiple tumors were observed, depending on gender, including lung, thyroid, mammary gland, liver, and kidney tumors (Cattley et al., 1994; NTP, 2002). Nitrobenzene is classified by IARC as a possible human carcinogen and by NTP as reasonably anticipated to be human carcinogen. The U.S. EPA has established environmental standards for nitrobenzene. Workplace standards and guidelines for nitrobenzene have been established by OSHA and ACGIH, respectively. The ACGIH recommends biological exposure indices to monitor workplace exposure. Information about external exposure (ie., environmental levels) and health effects is available from ATSDR at https://www.atsdr.cdc.gov/toxprofiles/index.asp.

Biomonitoring Information

Levels of nitrobenzene in blood reflect recent exposure. In the NHANES 2003-2004 and 2005-2006 subsamples, nitrobenzene was not detected. Finding a measureable amount of nitrobenzene in blood does not imply that the level of nitrobenzene causes an adverse health effect. Biomonitoring studies of blood nitrobenzene can provide physicians and public health officials with reference values so that they can determine whether or not people have been exposed to higher levels of nitrobenzene than levels found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.

References

Astier A. Simultaneous high-performance liquid chromatographic determination of urinary metabolites of benzene, nitrobenzene, toluene, xylene and styrene. J Chromatogr 1992;573(2):318-22.

Cattley RC, Everitt JI, Gross EA, Moss OR, Hamm TE Jr, Popp JA. Carcinogenicity and toxicity of inhaled nitrobenzene in B6C3F1 mice and F344 and CD rats. Fundam Appl Toxicol 1994;22(3):328-40. Erratum in: Fundam Appl Toxicol 1995;25(1):159.

International Agency for Research on Cancer (IARC). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 65. Printing Processes and Printing inks, Carbon black and Some Nitro Compounds. Summary of Data Reported and Evaluation 1996 [online]. Available at URL: http://monographs.iarc.fr/ENG/Monographs/vol65/volume65.pdf. 8/3/12

International Programme on Chemical Safety-INCHEM (IPCS). Environmental Health Criteria 230. Nitrobenzene. 2003 [online]. Available at URL: http://www.inchem.org/documents/ehc/ehc/ehc230.htm. 8/3/12

National Toxicology Program (NTP). Report on Carcinogens Background Document for Nitrobenzene. 2002 [online]. Available at URL: https://ntp.niehs.nih.gov/ntp/newhomeroc/roc11/NBPub.pdf. 8/3/12