Toxicology and Humoral Immunity Assessment of Octamethylcyclotetrasiloxane (D₄) Following a 28-day whole body Vapor Inhalation Exposure in Fischer 344 Rats

Abstract

Octamethylcyclotetrasiloxane, D4, is a low viscosity, silicone fluid consisting of four dimethyl-siloxy units ((CH3)2SiO)4 in a cyclic structure. It is primarily used as a building block in the industrial synthesis of long chain silicone polymers. The combination of D4 with decamethylcyclopentasiloxane (D5) is commonly referred to as cyclomethicone which has a wide range of applications as a formulation aid in personal care products. To extend the existing database regarding the biological activities of D4, a 28 day whole body vapor inhalation study was conducted using Fischer 344 rats at 0 (room air), 7, 20, 60, 180 and 540 ppm for 6 hours/day, 5 days/week. Parameters measured included body weights, organ weights, gross pathology, histopathology, serum chemistries, and urinalysis. In addition to these standard toxicological endpoints, the ability of D4 exposed animals to mount an IgM antibody response was evaluated by a splenic antibody forming cell (AFC) assay and a serum enzyme-linked immunosorbant assay (ELISA). The results of this 28-day inhalation study indicate that D4 exposure caused no adverse effects on body weight, food consumption, or urinalysis parameters. In addition, there were no exposure related histopathological alterations at any site for any exposure group. A statistically significant increase in liver weight and the liver to body weight ratio was observed in both male (180-540 ppm) and female (20-540 ppm) rats, which was not observed in the 14-day recovery group animals. There were no other significant organ weight changes. Although statistically significant changes were observed in several hematological and serum chemistry parameters in both the terminal and 14-day recovery animals, the changes were marginal and within the normal range of values for the rat. Under these experimental conditions, there were no alterations noted in immune system function at any of the D4 exposure levels.

Octamethylcyclotetrasiloxane (D4)

“…In a variety of in vivo and in vitro immunotoxicological studies, D4 was not found to significantly affect systemic immune responses. D4 was not immunotoxic in an inhalation and oral gavage study with F344 rats; however, thymus weight decreased in relation to D4 dosing (Klykken et al, 1999;Naim et al, 1995a;Nicholson et al, 1996b). D4 mixed with bovine serum albumin in an intramuscular study with dark Agouti rats (Nicholson et al, 1996a) and subcutaneous study with A/J mice resulted in a moderate humoral adjuvant effect with intense inflammation evident at the site of injection (DCC, 2001b;Naim et al, 1995b).…”

Safety Assessment of Cyclomethicone, Cyclotetrasiloxane, Cyclopentasiloxane, Cyclohexasiloxane, and Cycloheptasiloxane

“…According to Klykken et al, 18 the second largest use of cyclotetrasiloxane is in personal care products, such as, antiperspirants, deodorants, skin creams, and shampoos. In these applications, it is commonly blended with cyclopentasiloxane and is referred to as cyclomethicone.…”

“…D 4 is also used as a building block in the industrial synthesis of long chain silicone polymers. 18…”

“…Klykken et al 18 conducted a short-term inhalation toxicity study using groups of 25 Fischer-344 rats per sex, and the results are summarized in the Short-Term Inhalation Toxicity section reported later in the report text. Both test and control rats were exposed for 4 weeks (6 h/d, weekends excluded) to target concentrations of 0, 7, 20, 60, 180, and 540 ppm D 4 .…”

“…It was concluded that, under the experimental conditions of this study, D 4 did not cause alterations in immune system function up to the highest level of exposure, 540 ppm. 18…”