title: Chronic toxicity and oncogenicity of decamethylcyclopentasiloxane in the Fischer 344 Rat.
abstract: Decamethylcyclopentasiloxane (D5) is a cyclic polydimethylsiloxane used in the synthesis of silicon-based materials and as a component in consumer products. Male and female Fischer 344 rats were exposed to D5 vapor (0, 10, 40, 160 ppm; whole-body inhalation) for 6 h/d, 5 d/wk, for up to 104 weeks. Microscopic examination of tissues revealed test article effects at 160 ppm in the upper respiratory tract (hyaline inclusions in males and females at 6, 12, and 24 months) and an increased incidence of uterine endometrial adenocarcinoma at 24-months. The hyaline inclusions were considered a non-adverse tissue response for lack of any other respiratory tract non-neoplastic or neoplastic changes. Uterine endometrial adenocarcinoma was not anticipated. Toxicity testing (mutagenicity/genotoxicity, acute, sub-acute and sub-chronic descriptive toxicity) performed prior to the conduct of the chronic bioassay provided no indication that the uterus was a potential target organ. The target organ and tumor type specificity (adenocarcinoma is a common spontaneous tumor in the aged Fischer 344 rat) suggests the effect is associated with estrous cycle alteration. A robust assessment of potential mode(s) of action responsible for the uterine tumors and relevance to humans is addressed in a companion manuscript (Klaunig et al., 2015).
authors.affiliation: Dow Corning Corporation, 2200 West Salzburg Road, Midland, MI, 48686-0994, USA. Electronic address: paul.a.jean@dowcorning.com.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Jean
authors.affiliation: Dow Corning Corporation, 2200 West Salzburg Road, Midland, MI, 48686-0994, USA.
authors.forename: Kathleen P
authors.initials: KP
authors.lastname: Plotzke
authors.affiliation: Scialli Consulting, 3033 Wilson Blvd, Arlington, VA, 22201, USA.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Scialli
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced* / Q000473:pathology; D000280:Administration, Inhalation; D000818:Animals; D015197:Carcinogenicity Tests; D016889:Endometrial Neoplasms / Q000139:chemically induced* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000473:pathology; D005260:Female; D008297:Male; D011916:Rats, Inbred F344; D012137:Respiratory System / Q000187:drug effects / Q000473:pathology; D012833:Siloxanes / Q000493:pharmacokinetics / Q000633:toxicity*; D013045:Species Specificity; D036401:Toxicity Tests, Chronic
chemical_list: D012833:Siloxanes; C114768:decamethylcyclopentasiloxane
keywords: Adenocarcinoma; Bioassay; Decamethylcyclopentasiloxane; Oncogenicity; Reproductive; Siloxane; Uterine