The New Screening Levels
The May 2024 U.S. Environmental Protection Agency (EPA) regional screening levels (RSLs) include more stringent screening levels for 1-methylnapthalene in residential soil, industrial soil, and tap water, as well as new RSLs for residential air and industrial air (USEPA 2024a). The RSLs are based on EPA’s new provisional peer-reviewed toxicity values (PPRTVs) for 1-methylnaphthalene, released in March 2024, which include chronic and subchronic reference doses, chronic and subchronic reference concentrations (RfC), and a screening oral slope factor (OSF) (USEPA 2024b).
Where It Started
EPA’s database of potentially relevant studies informing the new PPRTVs for 1-methylnaphthalene is limited. Typically, PPRTVs are developed when data are insufficient to support a more definitive toxicity value (such as one derived by the EPA Integrated Risk Information program), and therefore are less certain than higher tier values.
Key Changes
- Introduction of Provisional Chronic RfC (p-RfC)
An important change to the 1-methylnaphthalene RSLs is the introduction of the PPRTV provisional chronic RfC (p-RfC), in that no RfC for 1-methylnaphthalene was previously included in the RSLs. EPA used the p-RfC to derive new residential air and industrial air RSLs for 1-methylnaphthalene (3.1 x 10-3 µg/m3 and 1.3 x 10-2 µg/m3, respectively). The chronic p-RfC, 3 × 10−6 mg/m3, is based on the subchronic point of departure in Kim et al. (2020), in which mucous cell hyperplasia was observed in the nasopharyngeal tissues of rats (USEPA 2024b, p. 35). EPA states that confidence in the chronic p-RfC for 1-methylnaphthalene is low due to the limitations of the study and the availability of only one study in the database (USEPA 2024b, p. 39).
- Update to Provisional Oral Slope Factor
EPA’s provisional 1-methylnaphthalene OSF increased from 2.0 x 10-2 to 5.10 x 10-2 per mg/kg-day. Thus, a 1 mg/kg increase in exposure is expected to increase cancer risk by 5 percent, or an additional 51 people in 1,000. For the updated p-OSF, EPA relied on an oral cancer bioassay for 1-methylnaphthalene (Murata et al. 1993), which EPA acknowledged as having “several limitations.” One such limitation is the possibility that volatilization of the test substance from the feed caused the observed lung tumors; historical control data were unavailable. Incidence of tumors was elevated only in males, and no concentration-response relationship was observed. Given these limitations, EPA only derived a provisional OSF. The 2008 p-OSF is slightly lower (i.e., less stringent) than the updated value; 2.0 x 10-2 per mg/kg-day is equivalent to an increased cancer risk of about 2 percent for every 1 mg/kg of exposure. The 2008 p-OSF was based on another cancer bioassay that dosed animals with 2-methylnaphthalene (Murata et al. 1997). There was no statistically significant increase in lung adenomas in either male or female mice fed 2-methylnaphthalene (Murata et al. 1997). Other toxicity reviews of both methylnaphthalenes (e.g., Lin et al. 2009) concluded the overall available evidence indicated a lack of carcinogenic potential.
What is the Impact?
The May 2024 RSL updates reduce residential soil, industrial soil, and tap water RSLs, as well as the risk-based soil screening level (SSL), for 1-methylnaphthalene by two orders of magnitude or more. Though cancer risk previously drove the residential soil, industrial soil, and tap water RSLs and risk-based SSL, the updates to the noncancer toxicity values cause all RSLs to now be based on noncancer points of departure. Further, 1-methylnapthalene RSLs for residential air and industrial air have now been introduced.
Conclusion
Integral scientists are at the forefront of regulatory toxicology developments. Our health scientists, including Claire Hamaji, MPH, and Heather Lynch, MPH, DABT, can help you navigate rapidly changing regulations.
References
Kim, Y.S., M.J. Lee, D.S. Seo, T.H. Kim, M.H. Kim, and C.H. Lim. 2020. Thirteen-week inhalation toxicity study of 1-methylnaphthalene in F344 rats. Toxicological Research 36:13–20. http://dx.doi.org/10.1007/s43188-019-00009-1.
Lin C.Y., A.M. Wheelock, D. Morin, et al. 2009. Toxicity and metabolism of methylnaphthalenes: Comparison with naphthalene and 1-nitronaphthalene. Toxicology 260(1–3):16–27. doi:10.1016/j.tox.2009.03.002.
Murata, Y., A. Denda, H. Maruyama, and Y. Konishi. 1993. Chronic toxicity and carcinogenicity studies of 1-methylnaphthalene in B6C3F1 mice. Toxicol. Sci. 21: 44–51. http://dx.doi.org/10.1093/toxsci/21.1.44.
Murata, Y., A. Denda, H. Maruyama, D. Nakae, M. Tsutsumi, T. Tsujiuchi, and Y. Konishi. 1997. Chronic toxicity and carcinogenicity studies of 2-methylnaphthalene in B6C3F1 mice. Fundam. Appl. Toxicol. 36:90–93. http://dx.doi.org/10.1006/faat.1996.2283.
USEPA. 2024a. Regional screening levels (RSLs) - Generic tables; Tables as of May 2024. Available at: https://www.epa.gov/risk/regional-screening-levels-rsls-generic-tables.
USEPA. 2024b. Provisional peer-reviewed toxicity values for methylnaphthalene,1-. EPA/690/R-24/017F. U.S. Environmental Protection Agency, Washington, DC. 101 pp.
