Table 3.

Chemical structure descriptors that were significantly negatively correlated with iPSC-derived cardiomyocyte bioactivity phenotypes after exposure to PFAS

Descriptor IDa	Phenotype(s)	N of Donorsb	N of Subst.c	Descriptor Meaning
Atoms
SGR10004	[-] Chronotrope	11	56	Fluorine (≥ 5 fluorine atoms present)
	Asystole	4
SGR10013	[-] Chronotrope	7	56	Any carbon
	Asystole	5
SGR10022	[-] Chronotrope	8	56	sp3 Carbon
	Asystole	5
SGR10029	[-] Chronotrope	10	56	Any non-carbon
	Asystole	4
	Cytotoxicity	2
SGR10043	[-] Chronotrope	12	56	Tetrasubstituted sp3 carbon
	Asystole	4
	Cytotoxicity	1
SGR10068d	[+] Chronotrope	1	9	Oxygen with two heavy atom substitutions
SGR10032d	[+] Chronotrope	2	3	Methyl-group
Atom Pairs
SGR10521	[-] Chronotrope	11	54	Two halogens, 3 bonds away (≥ 4 occurrences)
	Asystole	3
SGR10553	[-] Chronotrope	12	53	Two halogens, 4 bonds away (≥ 4 occurrences)
	Asystole	3
SGR10583	[-] Chronotrope	10	44	Two halogens, 5 bonds away (≥ 4 occurrences)
	Asystole	4
	Cytotoxicity	2
SGR10786d	[+] Chronotrope	5	8	OH-mediated intramolecular hydrogen-bonds
SGR10112d	[+] Chronotrope	4	7	Two oxygens, 3 bonds away
SGR10199d	[+] Chronotrope	2	3	Two oxygens, 5 bonds away
Bioavailability
SGR10261, SGR10780	[-] Chronotrope	13	56	F-C-F group (≥ 3 occurrences)
	Asystole	4
SGR10805	[-] Chronotrope	6	51	X-C-X moiety (X = O, N, or F)
	Asystole	3
SGR10633, SGR10708d	[+] Chronotrope	1	17	Primary alkyl bonded to O, N,S, or P atoms
SGR10275, SGR10295d	[+] Chronotrope	1	12	Primary alcohol
SGR10169d	[+] Chronotrope	1	8	Dialkyl ether
SGR10795d	Cytotoxicity	1	4	Primary carbon bonded to 2 fluorines
	Asystole	1
SGR10290d	[+] Chronotrope	5	3	Ethylene glycols and their mono-ethers
SGR10418, SGR10493, SGR10684, SGR10736 d	[+] Chronotrope	2	3	Secondary alcohol
SGR10354d	[+] Chronotrope	5	2	Isopropanol moiety
SGR10668d	[+] Chronotrope	3	2	Methoxy or methylamino group
Functional Groups
SGR10009 SGR10205	[-] Chronotrope	11	56	Fluorine bonded to aliphatic carbon (≥ 5 occurrences)
	Asystole	4
SGR10308	[-] Chronotrope	10	56	Potential hydrogen-bond acceptors (≥ 6 occurrences)
	Asystole	4
	Cytotoxicity	2
SGR10829	[+] Chronotrope	1	55	Potential hydrogen-bond donors
SGR10428	[-] Chronotrope	11	54	1,2-Dihalogenated ethyl (≥ 4 occurrences)
	Asystole	3
SGR10092	[-] Chronotrope	10	53	1,1,2,2-Tetrafluorinated ethyl
	Asystole	3
SGR10797	[-] Chronotrope	6	50	-CF2- or -O-CF- moiety
	Asystole	3
SGR10057	[-] Chronotrope	9	47	1,2,3-Trifluorinated propyl (≥ 6 occurrences)
	Asystole	3
SGR10072, SGR10761d	[+] Chronotrope	1	14	Hydroxyl attached to sp3 carbon
SGR10203d	[+] Chronotrope	1	8	Ether
SGR10153d	[+] Chronotrope	1	7	Sulfur bonded to 3 heavy atoms
SGR10109d	[+] Chronotrope	2	3	CH-OH moiety
SGR10343d	[-] Chronotrope	1	3	Any primary amine
SGR10289d	[+] Chronotrope	5	2	Ethylene glycol diol
SGR10587, SGR10099, SGR10703d	[+] Chronotrope	3	2	Sulfonamide
	Asystole	2
Topology
SGR10704d	Cytotoxicity	11	2	Polyether motifs as in PEGs
	[+] Chronotrope	2
SGR10749d	[+] Chronotrope	5	2	1,2-disubstituted ethanol

^a Saagar descriptors that were significantly correlated with iPSC-derived cardiomyocyte phenotypes can be found in Table S18. Correlation coefficients and corresponding q-values for the donors and phenotypes with significant (q < 0.1) associations can be found in Table S19

^b Number of donors with significant (q < 0.1) associations from a total of 16 tested

^c Number of PFAS with significant (q < 0.1) associations from a total of 56 tested

^d Saagar descriptors with corresponding structural features for each PFAS, highlighting the region that describes the particular Saagar descriptor can be found in Fig. S7