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Consequently, an in\u2010depth analysis was performed to determine if PCPs containing AMP pose an elevated risk in humans under the intended use conditions. Animal studies have shown that at high doses, oral AMP exposure could lead to liver steatosis; thus, this study focused on hepatotoxicity. Our assessment revealed that the derived margin of exposure (MoE) values for AMP\u2010containing PCPs were above 100, indicating that dermal exposure to AMP is unlikely to present an elevated risk of hepatotoxicity. Further, mode of action (MOA) analysis was conducted to elucidate the potential mechanisms underlying the observed hepatotoxicity in animal studies. Our analysis proposed that AMP interferes with the CDP\u2010choline pathway in hepatocytes via the inhibition of one or more enzymes integral to the pathway and\/or the replacement of choline in the assembly of the phospholipid unit. Ultimately, these events halt the lipid export via very low\u2010density lipoproteins, which can subsequently develop into fatty liver accompanied by hepatotoxicity and other pathological changes if AMP exposure persists at sufficiently high doses. MOA analysis corroborated that dermal exposure to AMP expected from use of PCPs is highly unlikely to result in toxicologically significant systemic concentrations of AMP and thus hepatotoxicity. We concluded that dermal exposure to AMP in PCPs is not anticipated to result in an increased risk of hepatotoxicity.<\/jats:p>","DOI":"10.1002\/jat.4308","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T22:09:47Z","timestamp":1645654187000},"page":"1873-1889","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dose and exposure route analyses inform relationships between liver steatosis and 2\u2010amino\u20102\u2010methyl\u20101\u2010propanol: Implications for hazard characterization"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7558-7860","authenticated-orcid":false,"given":"Lindsey","family":"Garnick","sequence":"first","affiliation":[{"name":"Cardno ChemRisk  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Bates","sequence":"additional","affiliation":[{"name":"Cardno ChemRisk  Blue Ash Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey","family":"Massarsky","sequence":"additional","affiliation":[{"name":"Cardno ChemRisk  Aliso Viejo California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela","family":"Spencer","sequence":"additional","affiliation":[{"name":"ANGUS Chemical Company  Mundelein Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanka","family":"Sura","sequence":"additional","affiliation":[{"name":"ANGUS Chemical Company  Buffalo Grove Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew D.","family":"Monnot","sequence":"additional","affiliation":[{"name":"Cardno ChemRisk  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Maier","sequence":"additional","affiliation":[{"name":"Cardno ChemRisk  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1680401"},{"key":"e_1_2_8_3_1","unstructured":"Angus Chemical Company (n.d.\u2010a)AMP\u201095\u2122; TDS No. 50.002\u2010E3 032719."},{"key":"e_1_2_8_4_1","unstructured":"Angus Chemical Company (n.d.\u2010b)AMP\u2010Ultra\u2122 PC; TDS No. 30.004\u2010E2 041921."},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2014.07.075"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(72)90166-4"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1091581809350932"},{"key":"e_1_2_8_8_1","unstructured":"Carney E.W. 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