. 2020 Sep 28;61(9):852–871. doi: 10.1002/em.22408

TABLE 3.

Point‐of‐departure (PoD) estimates for inhalation gene mutation studies and the corresponding permitted daily exposure (PDE) values

Study	Data set	Species and strain	Group size	Tissue	Endpoint	Exposure concentration	Frequency and duration	CI ^a BMDL (ppm)	CI BMD ^a (ppm)	Total UF ^b	PDE (ppt) from CI BMDL	PDE (ppt) from CI BMD
Manjanatha et al. (2017)	2	Mouse, big blue B6C3F1	10	LU	cII	0, 100, and 200 ppm	6 hr/day, 5 days/week; 8 weeks	8.1	20	3,162 ^c	2,547	6,409
Manjanatha et al. (2017)	3	Mouse, big blue B6C3F1	10	LU	cII	0, 100, 200 ppm	6 hr/day, 5 days/week; 12 weeks	25	35	1,581 ^d	15,924	22,407
Parsons et al. ( 2013 )	1	Mouse—big blue B6C3F1	10	LU	K‐ras	0, 10, 50, 100, and 200 ppm	6 hr/day, 5 days/week; 4 weeks	0.29	2.1	3,162 ^c	92	670
Parsons et al. ( 2013 )	2	Mouse—big blue B6C3F1	10	LU	K‐ras	0, 10, 50, 100, and 200 ppm	6 hr/day, 5 days/week; 4 weeks	0.19	1.2	3,162 ^c	60	375
Recio et al. (2004)	1	Mouse, B6C3F1	6	BM	lacI	0, 25, 50, 100, and 200 ppm	6 hr/days, 5 days/week; 48 weeks	5.5	15	316 ^e	17,505	47,344
Recio et al. (2004)	2	Mouse, B6C3F1	6	TE	lacI	0, 25, 50, 100, and 200 ppm	6 hr/day, 5 days/week; 48 weeks	0.09	0.45	316 ^e	285	1,434
van Sittert et al. (2000)	1	Rat—Lewis	6–8	SL	Hprt	0, 50, 100, and 200 ppm	6 hr/day, 5 days/week; 4 weeks	9	20	3,162 ^c	2,790	6,212
Walker et al. (1997)	1	Mouse, B6C3F1	7–9	SL	Hprt	0, 50, 100, and 200 ppm	6 hr/day, 5 days/week; 4 weeks	4	6.4	3,162 ^c	1,203	2,013

Note: Inhalation studies that reported variability of the data (SD or SEM) were used for PDE consideration are bolded. For reference (italicized), the PDE for inhalation studies that did not report variability were derived by dividing the BMDL by 5 (see the text).

Abbreviations: BM, bone marrow; CI, continuous inhalation; cII, cII mutation; Hprt, hprt mutation; lacI, lacI mutation; K‐ras, K‐ras mutation; LU, lung cells; SL, splenic lymphocytes; SP, splenocytes; TE, testes.

^{^a}

Modeled BMD and BMDL are adjusted to 24 hr/day and 7 days/week continuous exposure (see the text).

^{^b}

Total UF—total uncertainty factor based on F1 for interspecies toxicokinetic, F2 for inter‐individual variability, F3 for study duration, and F4 for effect severity (see the text).

^{^c}

Total UF based on F1 (TD only) 3.16, F2 10, F3 10, and F4 10.

^{^d}

Total UF based on F1 (TD only) 3.16, F2 10, F3 5, and F4 10.

^{^e}

Total UF based on F1 (TD only) 3.16, F2 10, F3 1, and F4 10.