Toxicological Review for 2-Methylnaphthalene (CAS No. 91-57-6 ...

Grimes and Young (1956) reported that urinary excretion was qualitatively similar among
rabbits, guinea pigs, and mice given 2-methylnaphthalene by gavage or by intraperitoneal injection, but
did not provide quantitative details.
3.5. PHYSIOLOGICALLY-BASED TOXICOKINETIC (PBTK) MODELING
No human or animal PBTK models were identified for 2-methylnaphthalene.
PBTK rat and mouse models have been developed for naphthalene (Ghanem and Shuler,
2000; NTP, 2000; Quick and Shuler 1999; Sweeney et al., 1996; Willems et al., 2001). The models
were designed for oral, inhalation, intraperitoneal, and intravenous exposure and are based on diffusion
rates and tissue partitioning coefficients as well as in vivo data for distribution, metabolism, and toxicity.
The models assume that naphthalene is metabolized only in the liver and lungs to naphthalene oxide (the
1,2-epoxide of naphthalene) and naphthalene oxide is metabolized only in the liver and lungs by
epoxide hydrolase (to dihydrodiols) or glutathione transferase (to glutathione conjugates).
The PBTK models for naphthalene in rodents are inadequate for predicting the toxicokinetics of
2-methylnaphthalene. An integral feature of the naphthalene models is the metabolism of naphthalene
exclusively to naphthalene oxide. In contrast, only 15-20% of 2-methylnaphthalene undergoes ring
epoxide formation, and 3 different isomers are produced (Melancon et al., 1982; Teshima et al., 1983).
Therefore, the models for naphthalene would not adequately predict the toxicokinetics of 80-85% of
the metabolites of 2-methylnaphthalene.
15