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Appendix D - Dossier (PDF) - Tera

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date: 20–JUL–2005<br />

5. Toxicity Substance ID: 71–43–2<br />

______________________________________________________________________________<br />

Reduced tumor resistance mediated via T–lymphocytes was<br />

observed in 9 out of 10 male C57Bl/6J mice exposed to 100<br />

ppm benzene (320 mg/m³) for a total of 100 days (6 hr/d, 5<br />

d/w, 20 weeks) and challenged with 10.00 polyoma<br />

virus–induced tumor cells/mouse. These mice developed tumors<br />

that were lethal. Lethal tumor incidences in air controls<br />

and mice exposed to 10 or 30 ppm benzene concentrations were<br />

3/10 or less.<br />

Source: German Rapporteur<br />

Flag: Risk Assessment<br />

06–JUL–2005 (960)<br />

Species: mouse Sex: male<br />

Strain: other: C57Bl/6<br />

Route of administration: inhalation<br />

Exposure period: 5 d prior to infection, additional subgroup with<br />

postinfectional exposure on 7 d<br />

Frequency of treatment: 6 h/d,<br />

Post exposure period: 7 d<br />

Doses: 10, 30, 100, 300 ppm followed by infection with<br />

Listeria monocytogenes<br />

NOAEL: 10 ppm<br />

Method: other<br />

Method: Host resistence test, 5–7 animals/group<br />

Result: Continuous exposure to concentrations as low as 30 ppm (96<br />

mg/m³) of benzene resulted in a delay in immune response of<br />

T–cells and macrophages after induction of bacterial<br />

infection in C57BL/6 mice (Rosenthal and Snyder 1985).<br />

Preexposure of male C57Bl/6J mice (5–7 animals/group) to<br />

benzene at 10, 30, 100, or 300 ppm for 5 days followed by<br />

infection with Listeria monocytogenes with continuous<br />

exposure on 7 days or without continuouing the exposure<br />

increased the bacterial counts in mice of the 300 ppm group<br />

of the preexposure group and in mice at 30, 100, and 300 ppm<br />

of the continuous exposure groups on day 4, but not days 1<br />

or 7. Nucleated cells, lymphocytes, T– and B–lymphocytes and<br />

monocytic/macrophagic cells per spleen increased from day 1<br />

to day 7 of infection in air control groups. Significant<br />

depressions of the mentioned cell types except the<br />

monocytic/macrophagic cells were observed in each exposure<br />

regimens at 30 ppm or higher concentrations from day 1<br />

through day 7 of bacterial infection.<br />

Source: German Rapporteur<br />

Flag: Risk Assessment<br />

06–JUL–2005 (959)<br />

<strong>Appendix</strong> D: Benzene SIDS <strong>Dossier</strong><br />

– 384/957 –

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