Appendix D - Dossier (PDF) - Tera

date: 20–JUL–2005
5. Toxicity Substance ID: 71–43–2
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Type: other: Study on absorption of environmental contaminants in
low–level exposure by pharmacokinetic analysis.
Remark: A dynamic generating toxic gas system and a nose–only
exposure system were used for the pharmacokinetic study of
inhaled environmental contaminants such as benzene, toluene,
xylene, ethylbenzene, chlorobenzene, styrene,
isopropylbenzene, tetrachloroethylene, nonane, and
methylcyclohexane in the male guinea pig. The change of
these substances in blood with time was detd. simultaneously
by solid phase microextn. (SPME)–gas chromatog. (GC). The
fraction of absorption of benzene at low (121 microgram/m3)
exposure was 4.8 times higher than that at high (12.1 mg/m3)
exposure. The pharmacokinetics of these substances was
evaluated by using linear compartment models. More styrene
was absorbed than tetrachloroethylene at low exposure. The
metabolic elimination of these compds. at various exposure
concns. was extrapolated by using estd. pharmacokinetic
parameters. The results showed that the exposure concns. in
gas for all chems. were equal, and the differences in
absorption quantities and metabolic elimination rates may be
simultaneously considered in evaluation of potential risk
assessment. The fundamental data used for risk assessment
were presented.
Source: ExxonMobil Biomedical Sciences Inc. Annadale, New Jersey
14–FEB–2002 (480)
Type: other: Development of liquid chromatography–electrospray
ionization–tandem mass spectrometry methods for determination
of urinary metabolites of benzene in humans.
Remark: To investigate the ways in which different levels of
exposure affect the metabolic activation pathways of benzene
in humans, and to examine the relationship between urinary
metabolites and other biological markers, we have developed
two sensitive and specific liquid chromatography–tandem mass
spectrometry (LC–MS/MS) assays for quantitation of the
benzene metabolites trans,transmuconic acid (t,t–MA),
S–phenylmercapturic acid (S–PMA), hydroquinone (HQ),
catechol (CAT), and for estimation of
1,2,4–trihydroxybenzene (BT). In our first assay, urinary
S–PMA and t,t–MA were measured simultaneously by liquid
chromatography–electrospray ionization–tandem mass
spectrometry–selected reaction monitoring (LC–ESI–MS/MS–SRM)
in the negative ionization mode. In this assay, the
metabolites [13C6]–S–PMA and [13C6]–t,t–MA were used as
internal standards. The efficacy of this specific assay was
evaluated in human urine specimens from 28 smokers and 18
nonsmokers serving as the benzene–exposed and nonexposed
groups, respectively. The coefficient of variation (CV) of
analyses on different days (n = 8) for S–PMA was 7% for
samples containing 9.4 micrograms/L urine, and for t,t–MA
was 10% for samples containing 0.07 mg/L. The mean levels of
S–PMA and t,t–MA in smokers were 1.9–fold (p = 0.02) and
2.1–fold (p = 0.03) higher, respectively, than those in
nonsmokers.
Appendix D: Benzene SIDS Dossier
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