Octamethylcyclotetrasiloxane

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Reference 2

Reference Type:

publication

Title:

Quantitative Exposure of Humans to an Octamethylcyclotetrasiloxane (D4) Vapor

Author:

Utell et al.

Year:

1998

Bibliographic source:

Toxicol. Sci. 44, 206-213

Materials and methods

Type of study / information:

Type of experience: Human

Endpoint addressed:

basic toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Pharmacokinetics of D4 vapor in humans

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Octamethylcyclotetrasiloxane

EC Number:

209-136-7

EC Name:

Octamethylcyclotetrasiloxane

Cas Number:

556-67-2

Molecular formula:

C8H24O4Si4

IUPAC Name:

2,2,4,4,6,6,8,8-octamethyl-1,3,5,7,2,4,6,8-tetroxatetrasilocane

Method

Details on study design:

Respiratory intake and uptake of D4 were measured in 12 healthy volunteers (25 - 49 years) on two occasions. Subjects inhaled 10 ppm D4 (122 µg/l) or air (control) during a 1-h exposure via a mouthpiece in a double-blind, randomized fashion. Inspiratory and expiratory D4 concentrations were continuously measured. Exhaled air and plasma D4 levels were measured before, during and after exposures. Individual D4 uptakes were measured under steady-state conditions during three rest periods (10, 20, and 10 min, respectively) alternating with two 10-min exercise periods.

Exposure assessment:

measured

Results and discussion

Results:

Mean D4 intake was 137 +/- 25 mg (SD) and the mean deposition efficiency was  equivalent to 0.74/(1 + 0.45 VE) where VE is the minute ventilation. No changes in lung function were induced. Plasma measurement of D4 gave a mean peak value of 79 +/- 5 ng/g (SEM) and indicated a rapid nonlinear blood clearance. Using lung volume and respiratory surface area estimates based on functional residual capacity measurements a model was developed and determined that the effective mass transfer coefficient for D4 was 5.7 x 10-5 cm/s from lung air to blood. In an additional eight subjects D4 deposition at resting ventilations were compared with mouthpiece and nasal breathing. Mean deposition was similar for the two exposure protocols, averaging 12 % after correction for exposure system losses.

Applicant's summary and conclusion

Conclusions:

In a human clinical study (reliability score 2), the respiratory intake and uptake of D4 were measured in 12 healthy volunteers following exposure to 10 ppm for 1 hour. Mean D4 intake was 137 +/- 25 mg (SD). Plasma measurement of D4 gave a mean peak value of 79 +/- 5 ng/g (SEM) and indicated a rapid nonlinear blood clearance.