Acetonitrile

Immunotoxicity

Description of key information

Limited immunotoxicity data are available for acetonitrile.  The reliability of these data is unclear.  The available data do not indicate a unique concern for immunotoxic effects of acetonitrile exposure.  In a 1999 review of these studies, the US EPA chose to withdraw use of the data for human risk assessment, stating: Inasmuch as (1) these hematological and hepatocellular effects were of questionable biological significance, (2) hematological parameters were unaffected in the NTP (1996) subchronic and chronic rat study (these parameters were not measured in the mouse portion of the study), and (3) hepatic vacuolization was not observed in the chronic mouse study, it was recommended that the RfD for ACN [based on these data] be withdrawn from IRIS.  Given these conclusions by EPA and questions that exist about the availability and reliability of the main Hazleton study from which the animals were taken, the Immunquest study was disregarded in this assessment.

Additional information

In an immunotoxicity study conducted for the US National Toxicology Program,(1983) reported that hematologic parameters including hematocrit, hemoglobin, erythrocyte counts and leukocyte counts were depressed in female mice after 10 days of exposure to 100, 200 or 400 ppm acetonitrile vapor. These changes were dose related, but statistically significant only in the 200 and 400 ppm groups. IgG levels were significantly decreased in all exposed groups in a dose-related manner. Lymphocyte proliferation to T-cell mitogens PHA and Con A were depressed, although these responses were not dose dependent. No exposure-related effects were apparent in delayed hypersensitivity response. Host resistance to transplantable PYB6 tumor challenge was not altered. These results were part of a 90 -day mouse inhalation study conducted by (1983) for the US National Toxicology Program. The study was repeated, the results were not published by NTP, and the study is not identified in the public NTP database. The reasons are not clear; but are considered to be an indication that NOAELs cannot be established based upon these study results.

In a study reported by Immunoquest (1984) and cited by EPA (1999), female mice were exposed to acetonitrile by inhalation at concentrations of 0, 100, 200 or 400 ppm, 6 hours/day, for 10 days during a 14 -day period. Serum IgG concentrations were significantly decreased in a concentration-dependent manner. Hematology parameters were significantly decreased, and thymic atrophy noted at the 200 and 400 ppm levels. Tests of B-cell function were similar to controls. The relationship of this study to that of(1983) above is not clear.

No effects were noted on lymphopoietic tissues in the subchronic or chronic NTP rat and mouse studies. No significant hematological changes were noted in rats; hematology parameters were not investigated in the NTP mouse studies.

In a 1999 review of these studies, the US EPA chose to withdraw use of the data for human risk assessment, stating:Inasmuch as (1) these hematological and hepatocellular effects were of questionable biological significance, (2) hematological parameters were unaffected in the NTP (1996) subchronic and chronic rat study (these parameters were not measured in the mouse portion of the study), and (3) hepatic vacuolization was not observed in the chronic mouse study, it was recommended that the RfD for ACN [based on these data] be withdrawn from IRIS.

 

Justification for classification or non-classification

No classification is proposed based on the limited data available and uncertainty regarding reliability.