Toxicological Review of n-Hexane (CAS No. 110-54-3) (PDF)

in fat would require more than 10 days of no further exposure.
Perbellini et al. (1990) used their approach to evaluate the likely impact on the biological
exposure index (BEI) of the 50 ppm threshold limit value (TLV) proposed for n-hexane for
1988–1989 by the American Conference of Governmental Industrial Hygienists (ACGIH, 2003).
As simulated by the model, urinary concentrations of 2,5-hexanedione ranged from 2.4 to
2.9 mg/L before the start of the first shift of the work week and from 3.3 to 4.3 mg/L on the
morning of the following work days. Fisher et al. (1997) used a generic human lactation PBTK
model that was developed using published human and animal PBTK model parameters to
simulate the transfer of 19 volatile chemicals, including n-hexane, from a nursing mother to her
infant during breast feeding. The model was used to estimate the amount of chemical that would
be transferred during a given nursing schedule, assuming resumed occupational exposure after
childbirth and maternity leave. Specifically, the five-compartment model of Ramsey and
Andersen (1984) was adapted by the incorporation of a milk compartment that changed in
volume in response to a nursing infant. For n-hexane, rodent tissue solubility and allometrically
scaled metabolic rate constants available in the published literature were used to estimate human
tissue metabolic parameters for the model. Blood:air and milk:air partition coefficients were
determined by running the model for a simulated maternal exposure at the TLV of 50 ppm
n-hexane. This simulation predicted the amount of chemical that would be ingested by an infant
over a 24-hour period. The amount of n-hexane ingested by an infant was 0.052 mg (Fisher et
al., 1997). The Fisher et al. (1997) model does not specifically address target tissues or
extrapolate between species or routes and has not been validated. n-Hexane levels in breast milk
have not been quantified for measured exposures to n-hexane. The authors suggested that the
absence of exposure and toxicokinetic data on lactational transfer of chemicals such as n-hexane
to nursing infants is a disadvantage of this model.
24