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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 />

4 h after treatment of HL60 cells with 50, 75 and 100 microM<br />

MUC. No increases in DNAPC levels were measured in HL60<br />

cells 4 h after treatment with the MUC metabolites<br />

6–hydroxy–trans,trans–2,4–hexadienal (HO–M–CHO),<br />

6–oxo–trans,trans–2,4–hexadienoic acid (CHO–M–COOH), or<br />

trans,trans–muconic acid (HOOC–M–COOH), each at 100 microM.<br />

Significant increases in DNAPC levels were obsd. 4 h after<br />

treatment with 500 and 1000 microM HO–M–CHO, but not<br />

CHO–M–COOH. No effect on DNAPC levels was obsd. 4 h after<br />

treatment with 100 microM for trans,trans–2,4–hexadienal,<br />

trans–2–hexenal, hexanal, trans,trans–2,4–hexadiene,<br />

glutaraldehyde, or acrolein. DNAPC induced by MUC and<br />

HO–M–CHO may be cytotoxic lesions, as increases in DNAPC<br />

levels by these compds. correlated with decreases in cell<br />

viability. Except for acrolein, compds. not inducing DNAPC<br />

at 100 microM also did not affect cell viability. These<br />

studies suggest that both aldehydic carbons of MUC<br />

contribute to DNAPC induction, and that the presence of<br />

alpha,beta–unsatd. double bonds conjugated with the aldehyde<br />

groups increases the ability of MUC to induce DNAPC relative<br />

to the satd. dialdehyde glutaraldehyde.<br />

Source: ExxonMobil Biomedical Sciences Inc. Annadale, New Jersey<br />

14–FEB–2002 (1026)<br />

Type: other: Benzene percutaneous absorption: dermal exposure<br />

relative to other benzene sources.<br />

Remark: Skin is one of several exposure routes whereby benzene, a<br />

widely distributed environmental contaminant that causes<br />

leukemia, enters the body, so accurate predictions of its<br />

percutaneous absorption are important for risk assessment.<br />

Determining benzene’s skin–exposure dose and subsequent<br />

absorption is difficult because it has a low boiling point<br />

and exists as both liquid and vapor. Industrial and<br />

environmental benzene is present as a contaminant in other<br />

vehicles/solvents, and its percutaneous absorption is in<br />

part dependent upon co–solvent volatility. Co–solvents such<br />

as benzene in toluene rapidly evaporate from skin, whereas<br />

benzene contaminant in water is retained on skin longer due<br />

to water’s lower volatility. Co–solvents can also affect<br />

benzene–skin partition coefficients; thus, permeability<br />

coefficients and percentage doses absorbed can vary<br />

many–fold. The exposure situation will determine<br />

percutaneous absorption, which, if low, can be overwhelmed<br />

by benzene intake from the food we eat and the air we<br />

breathe.<br />

Source: EXXON Biomedical Sciences East Millstone, NJ<br />

Reliability: (1) valid without restriction<br />

21–JUL–2000 (1246)<br />

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

– 792/957 –

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