Acute Respiratory Exposure of Human Volunteers to Octamethylcyclotetrasiloxane (D4): Absence of Immunological Effects

Looney, R. John; Frampton, Mark W.; Byam, Jerome; Kenaga, C.; Speers, Donna M.; C, Cox; Mast, Richard; Klykken, Paal C.; Morrow, Paul E.; Utell, Mark J.

doi:10.1006/toxs.1998.2484

Cited by 8 publications

(8 citation statements)

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“…If D 4 exposures were repeated in either case at a frequency shorter than the fat half-life, the net result would be accumulation in the fat tissues, because the input would exceed the elimination output. These results were not evident from previous human exposure studies, because the target tissue disposition was not accurately determined (17,18). Utell et al (17) exposed human volunteers to 129-137 mg D 4 ; the lungs only captured 10% of D 4 exposure by inhalation (13 mg out of 129-137 mg of inhaled D 4 ).…”

Section: Discussionmentioning

confidence: 93%

“…The model was first calibrated using previously reported data on tissue distribution in female rats after single and repeated IV administrations of 14 C-D 4 (1). We validated the predicted results in rats and in humans after inhalation exposure using published independent data (12,17,18). We then used the validated model to predict the pharmacokinetics of D 4 as leached from saline-filled breast implants in women.…”

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confidence: 99%

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Bioavailability of octamethylcyclotetrasiloxane (D(4)) after exposure to silicones by inhalation and implantation.

Luu

Hutter

2001

Environ Health Perspect

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We developed a physiologically based pharmacokinetic (PBPK) model to predict the target organ doses of octamethylcyclotetrasiloxane (D(4)) after intravenous (IV), inhalation, or implantation exposures. The model used (14)C-D(4) IV disposition data in rats to estimate tissue distribution coefficients, metabolism, and excretion parameters. We validated the model by comparing the predicted blood and tissues concentrations of D(4) after inhalation to experimental results in both rats and humans. We then used the model to simulate D(4) kinetics after single and/or repeated D(4) exposures in rats and humans. The model predicted bioaccumulation of D(4) in fatty tissues (e.g., breast), especially in women. Because of its high lipid solubility (Log P(oct/water) = 5.1), D(4) persisted in fat with a half life of 11.1 days after inhalation and 18.2 days after breast implant exposure. Metabolism and excretion remained constant with repeated exposures, larger doses, and/or different routes of exposure. The accumulation of D(4) in fatty tissues should play an important role in the risk assessment of D(4) especially in women exposed daily to multiple personal care products and silicone breast implants.

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Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

Bioavailability of octamethylcyclotetrasiloxane (D(4)) after exposure to silicones by inhalation and implantation.

Luu

Hutter

2001

Environ Health Perspect

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“…A number of tests to speci cally evaluate the potential impact of D 4 on the mammalian immune system have been completed. No effects on the immune system occurred when rats were exposed repeatedly to a very high concentration of D 4 vapors (Klykken et al 1999) or when humans were exposed for 1 hour to the industrial hygiene guideline concentration of 10 ppm (Looney et al 1998). In addition, the metabolism and toxicokinetics of this material in mammalian systems has recently begun to be elucidated (Varaprath et al 1998(Varaprath et al , 1999(Varaprath et al , 2000Plotzke et al 1995Plotzke et al , 1996Plotzke et al , 2000Salyers et al 1996;Seaton et al 1997;Utell et al 1998).…”

Section: Figurementioning

confidence: 99%

“…D 4 has been extensively studied for its toxic effects in microorganisms, cell cultures, and animals. Some studies in humans also have been performed (Utell et al 1998;Looney et al 1998). Based on laboratory tests for acute toxicity, D 4 was found to have low toxicity by oral ingestion, prolonged skin contact, or upon inhalation of its vapor or its aerosol form.…”

Section: Figurementioning

confidence: 99%

Inhalation Toxicology of Octamethylcyclotetrasiloxane (D₄) Following a 3-Month Nose-Only Exposure in Fischer 344 Rats

et al. 2002

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Octamethylcyclotetrasiloxane (D4) is a low-molecular-weight cyclic siloxane used primarily in the synthesis of silicone polymers. The objective of the present study was to evaluate the subchronic toxicity of D4 following a 3-month nose-only inhalation exposure. Male and female Fischer 344 rats (20/sex/group) were exposed 6 h/day, 5 days/week for 3 months to vapor concentrations of 0, 35, 122, 488, and 898 ppm D4. Also, an additional 10 per sex in the control and high-exposure groups were allowed a 4-week recovery period to observe reversibility, persistence, or delayed occurrence of any potential adverse effects. Body weights and food consumption were monitored at least twice weekly over the course of exposures. Approximately 18 hours preceding euthanasia, animals were transferred into metabolism cages for urine collection, and were fasted. At necropsy, rats were anesthetized with pentobarbital and euthanized by exsanguination. Blood was collected for hematological and clinical biochemical analyses. Selected organ weights were measured and a complete set of tissues was taken for histopathological examination. A concentration-dependent increase in absolute and relative liver weight (488 to 898 ppm) and a significant decrease in ovarian weight (898 ppm) were observed in female rats. Exposure to D4 via nose-only inhalation (35 to 898 ppm) produced minor alterations in hematological and serum chemistry parameters that were considered either incidental and of little toxicological significance (hematology) or suggestive of metabolic adaptation/alteration (serum chemistry) in response to exposure-related hepatomegaly. There were no histopathological findings noted in the liver. Histopathological evidence indicated the primary target organs following D4 inhalation exposure to be components of the female reproductive tract. Reversible histopathological changes were observed in the ovary (hypoactivity) and vagina (mucification) of female rats in the high-dose group only (898 ppm). Although an increase in the incidence and severity of both macrophage accumulation, interstitial inflammation, and eosinophil infiltration was observed in the lungs of male and female rats exposed to D4, the toxicological significance is uncertain as other inhalation studies at similar concentrations failed to show these effects. In summary, nose-only inhalation of a high concentration of D4 resulted in reversible histopathological changes in the female rat reproductive tract. Lower concentrations did not elicit these same effects.

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“…Siloxanes are used widely in consumer products, such as paints, cosmetics, and household products, as well as in medical products. Recently, however, various studies have pointed out that some siloxanes may have endocrine disrupting properties and effects on reproduction, which may cause concern regarding their effects on humans and the environment [ 21 , 22 , 23 ]. The first step related to a hazard assessment is to collect and generate information on the intrinsic properties of the ingredients and determine the toxicological endpoints, including taking the use pattern and routes of exposure into account.…”

Section: Introductionmentioning

confidence: 99%

Health Risk Assessment on Hazardous Ingredients in Household Deodorizing Products

Lee

Kim

Lee

et al. 2018

IJERPH

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The inhalation of a water aerosol from a humidifier containing disinfectants has led to serious lung injuries in Korea. To promote the safe use of products, the Korean government enacted regulations on the chemicals in various consumer products that could have adverse health effects. Given the concern over the potential health risks associated with the hazardous ingredients in deodorizing consumer products, 17 ingredients were analyzed and assessed according to their health risk on 3 groups by the application type in 47 deodorizing products. The risk assessment study followed a stepwise procedure (e.g., collecting toxicological information, hazard identification/exposure assessment, and screening and detailed assessment for inhalation and dermal routes). The worst-case scenario and maximum concentration determined by the product purpose and application type were used as the screening assessment. In a detailed assessment, the 75th exposure factor values were used to estimate the assumed reasonable exposure to ingredients. The exposed concentrations of seven ingredients were calculated. Due to limitation of toxicity information, butylated hydroxyl toluene for a consumer’s exposure via the dermal route only was conducted for a detailed assessment. This study showed that the assessed ingredients have no health risks at their maximum concentrations in deodorizing products. This approach can be used to establish guidelines for ingredients that may pose inhalation and dermal hazards.

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Acute Respiratory Exposure of Human Volunteers to Octamethylcyclotetrasiloxane (D4): Absence of Immunological Effects

Cited by 8 publications

References 20 publications

Bioavailability of octamethylcyclotetrasiloxane (D(4)) after exposure to silicones by inhalation and implantation.

Bioavailability of octamethylcyclotetrasiloxane (D(4)) after exposure to silicones by inhalation and implantation.

Inhalation Toxicology of Octamethylcyclotetrasiloxane (D₄) Following a 3-Month Nose-Only Exposure in Fischer 344 Rats

Health Risk Assessment on Hazardous Ingredients in Household Deodorizing Products

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Acute Respiratory Exposure of Human Volunteers to Octamethylcyclotetrasiloxane (D4): Absence of Immunological Effects

Cited by 8 publications

References 20 publications

Bioavailability of octamethylcyclotetrasiloxane (D(4)) after exposure to silicones by inhalation and implantation.

Bioavailability of octamethylcyclotetrasiloxane (D(4)) after exposure to silicones by inhalation and implantation.

Inhalation Toxicology of Octamethylcyclotetrasiloxane (D4) Following a 3-Month Nose-Only Exposure in Fischer 344 Rats

Health Risk Assessment on Hazardous Ingredients in Household Deodorizing Products

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Inhalation Toxicology of Octamethylcyclotetrasiloxane (D₄) Following a 3-Month Nose-Only Exposure in Fischer 344 Rats