Safe human exposure limits for airborne linear siloxanes during spaceflight

Figures & data

Table 1. Chemical and physical properties of linear siloxanes.

	Hexamethyl-disiloxane (L2)	Octamethyl-trisiloxane (L3)	Decamethyl-tetrasiloxane (L4)	Dodecamethyl-pentasiloxane (L5)
Structure
Formula	C6–H18–O–Si2	C8–H24–O2–Si3	C10–H30–O3–Si4	C12–H36–O4–Si5
CAS Registry #	107-46-0	107-51-7	141-62-8	141-63-9
Molecular Weight	162.38	236.53	310.69	384.84
Physical State	Clear, colorless liquid	Clear, colorless liquid	Clear, colorless liquid	Clear, colorless liquid
Boiling Point (°C)	99	152	194	232
Melting Point (°C)	−66	−82	−68	−80
log Kow	4.2	4.8	5.4	6
Vapor pressure at 25°C (torr)	42	3.9	0.4	0.1
Saturated vapor concentration (ppm)^a	55 300	5131	530	130

Information obtained from NCBI PubChem: http://pubchem.ncbi.nlm.nih.gov/.

^aSaturated vapor concentration = (VP/760) × 10⁶.

Figure 1. Astronaut Jerry Linenger with personal hygiene items onboard the Russian Space Station MIR.

Table 2. Summary of previously published octamethyltrisiloxane (L3) SMAC values and the critical adverse effect (Henderson & James, 1994).

Octamethyltrisiloxane
1-hour SMAC	24-hour SMAC	7-day SMAC	30-day SMAC	180-day SMAC
400 ppm	200 ppm	100 ppm	20 ppm	4 ppm
Lethality	Hepatotoxicity	Hepatotoxicity	Hepatotoxicity	Hepatotoxicity
	Nephrotoxicity	Nephrotoxicity	Nephrotoxicity	Nephrotoxicity

Table 3. Summary of new studies.

Test article	Strain; number of animals	Exposure duration	Target exposure levels (ppm)	Results	NOAEL/BMDL	Reference
Acute
L2	F-344 rats 5/sex/dose	Single 4 hr	11 000, 14 000, 18 000	Death: 6/10 at 18 000 ppm, 2/10 at 14 000 ppm, 0/10 at 11 000 ppm; Local respiratory effects and neurological dysfunction at 18 000 and 14 000 ppm	11 000 ppm	DCC (1996)
L3	SD rats 5/sex/dose	Single 4 hr	2350	No adverse treatment-related effects	2350 ppm	DCC (2004a)
Subacute
L3	SD rats 10/sex/dose	6 hr/day 5 day/week 28 days (females) 29 days (males)	0, 800, 1600, 3200	Hepatic porphyrins in males at 1600 and 3200 ppm; Increased liver weights in males at 3200 ppm and in females at 800, 1600, and 3200 ppm^a	594 ppm (BMDL)	DCC (2007a)
L4	SD rats 10/sex/dose	6 hr/day 5 day/week 28 days (females) 29 days (males)	0, 400	No adverse treatment-related effects	400 ppm^e	DCC (2007b)
Subchronic
L2	F-344 rats 20/sex/dose	6 hr/day 5 day/week 13 weeks	0, 50, 200, 600, 1500, 5000	Male-specific hyaline casts at 600, 1500, and 5000 ppm^b	5000 ppm	DCC (1998, Cassidy (2001)
L2	SD rats 30/sex/dose	6 hr/day 7 day/week 146 days (F0 males) 138 days (F1 males)^c 163 days (F0 females) 159 days (F1 females)^c	0, 100, 400, 1600, 5000	Subtle neurological endpoints noted in offspring^c; Male-specific hyaline casts at 5000 ppm^b; Hepatic porphyrins, periportal inflammation, and bile duct hyperplasia at 5000 ppm in the F0 generation	1600 ppm	DCC (2006, DCC (2008)
L3	SD rats 10/sex/dose	6 hr/day 7 day/week 90 days	0, 95, 400, 3200	Hepatic porphyrins in males at 3200 ppm; Increased liver weight in males at 400 and 3200 ppm^a; Periportal inflammation in 10 males/1 female at 3200 ppm, 1 male/1 female at 400 ppm, 1 female at 95 ppm, and 1 male/1 female control^d	400 ppm	DCC (2010a)
L4	SD rats 10/sex/dose	6 hr/day 7 day/week 90 days	0, 70, 400	No adverse treatment-related effects	400 ppm^e	DCC (2010b)
Chronic
L2	F-344 rats 20/sex/dose	6 hr/day 5 day/week 24 months	0, 100, 400, 1600, 5000	Male-specific hyaline casts at 5000 ppm^b; Increased liver weights in males at 1500 and 5000 ppm^a; Leydig cell tumors in all males (including controls)^d	5000 ppm	DCC (2004b)

^aConsidered adaptive metabolic response, rather than adverse effect, due to lack of histopathological findings.

^bConsidered irrelevant to human risk assessment.

^cNASA does not consider developmental endpoints since astronauts are screened for pregnancy prior to flight, and conception is not expected during flight.

^dConsidered irrelevant to human risk assessment and not test article related.

^eHighest achievable vapor concentration.

Figure 2. Quantal-linear model rejected due to poor fit for 7-day SMAC endpoint (porphyrin).

Figure 3. Log-probit model selected as the best fit for potential hepatotoxicity due to porphyrin deposits for 7-day SMAC development.

Table 4. Summary of benchmark dose modeling output for 7-day SMAC development.

Model	Gamma	Logistic	Log-logistic	Log-probit	Multistage (2)	Multistage (3)	Probit	Weibull	Quantal-linear
p Value	0.3548	0.1298	0.4837	0.4854	0.4770	0.2683	0.1418	0.2667	0.1298
Scaled residual	−0.822	−1.054	−0.725	−0.677	−1.286	−1.189	−1.043	−1.09	0
AIC	26.562	28.704	25.804	25.773	25.857	27.801	28.690	27.610	30.708
BMDL	479.43	538.22	572.00	593.68	303.04	281.91	514.32	364.56	150.42

The value in bold is the value that resulted from the best-fitting model and selected for derivation of the SMAC.

Table 5. Summary of updated SMAC values for linear siloxanes and the critical adverse effect.

Linear siloxanes
1-hour SMAC	24-hour SMAC	7-day SMAC	30-day SMAC	180-day SMAC	1000-day SMAC
600 ppm	100 ppm	100 ppm	50 ppm	50 ppm	50 ppm
Pulmonary/neurotoxcity	Pulmonary/neurotoxcity	Hepatotoxicity	Hepatotoxicity	Hepatotoxicity	Hepatotoxicity

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