reaction mass of ethylbenzene and m-xylene and p-xylene

Immunotoxicity

Description of key information

An 28-day inhalation study in female rats specifically designed to detect immunological effects (according to the EPA OPPTS 870.7800 guideline) is available (WIL Research Laboratories Inc., 2004; Li et al., 2007). No adverse effects were found on the functional ability of the humoral immune system at exposure concentrations of ethylbenzene up to 500 ppm.

Additional information

A 28-day inhalation study in female rats specifically designed to detect immunological effects (according to the EPA OPPTS 870.7800 guideline) has already briefly been mentioned in the section for repeated dose toxicity (WIL Research Laboratories Inc., 2004; Li et al., 2007). 10 animals/dose were exposed 7 d/week at 25, 100, 500 ppm. Cyclophosphamide was used as positive control substance given by ip injection in saline over 4 consecutive days. After immunization with sheep red blood cells IgM antibodies and splenic antibody-forming cells were determined. Hematology was carried out and specifically spleen and thymus weights were measured. No adverse effects were found on the functional ability of the humoral immune system at exposure concentrations of ethylbenzene up to 500 ppm. The positive control substance, cyclophosphamide, performed as expected exhibiting a decrease in spleen and thymus weights, a decrease in spleen cell numbers and a decrease in IgM Antibody Forming Cell Response.  

 

The negative findings in the study specifically designed for immunotoxicity testing are corroborated by the results of standard repeated dose studies: no adverse effects were observed in bone marrow, lymph nodes, spleen, and thymus in the 2-year bioassay in rats and mice by inhalation up to 750 ppm (NTP, 1999), in the 13-week inhalation study in rats and mice up to 1000 ppm including hematology in rats (NTP, 1992), or in the 13-week oral gavage study in rats at doses up to 750 mg/kg bw/d including (organs such as liver, kidneys, adrenals, testes, epididymes, ovaries, uterus, spleen, brain, heart, thymus) and hematology (Mellert et. al., 2007).

Justification for classification or non-classification

Based on the absence of immune system effects in a 28 day inhalation toxicity study in rats, no classification for immune system effects is warranted for ethylbenzene.