National Toxicology Program

TR-239
Carcinogenesis Bioassay of Bis(2-chloro-1-methylethyl)ether (~70%) (CAS No. 108-60-1) Containing 2-Chloro-1-methylethyl(2-chloropropyl)ether (~30%) (CAS No. 83270-31-9) in B6C3F₁ Mice (Gavage Study)

Bis(2-chloro-1-methylethyl) ether is a beta-haloether that has been used extensively in paint and varnish removers, spotting agents, and cleaning solutions. BCMEE has also been used as an intermediate in the manufacture of dyes, resins, and pharmaceuticals and has been added to soap solutions to aid in textile cleaning. Bis (2-chloro-1- methylethyl) ether has been a by-product in the manufacture of propylene oxide and propylene glycol. It is the active ingredient of a nematocide developed and used on field crops in Japan.

A carcinogenesis bioassay of bis (2-chloro- 1-methylethyl) ether (~70%), containing ~30% 2-chloro-1- methylethyl (2-chloropropyl) ether, was conducted by administering 100 or 200 mg/kg bis (2-chloro- 1-methylethyl) ether in corn oil by gavage 5 times per week for 103 weeks to groups of 50 B6C3F₁ mice of each sex. Fifty mice of each sex received corn oil alone and served as vehicle controls. Survival and mean body weights of dosed and control mice of each sex were comparable.

The incidence of alveolar/bronchiolar adenomas occurred in a positive dose-related trend for male mice (P<0.05: control 5/50, 10%; low-dose 13/50, 26%; high-dose 11/50, 22%) and for female mice (P<0.02: 1/50, 2%; 4/50, 8%; 8/50, 16%). The number of female mice in the high-dose group with adenomas was significantly (P<0.03) greater than that in controls. The combined incidences in dosed males and in high-dose females were significantly higher (P<0.04 for males and P<0.01 for females) than those in the controls (males: 6/50, 12%; 15/50, 30%; 13/50, 26%; females: 1/50, 2%; 4/50, 8%; 10/50, 20%).

The incidence of hepatocellular carcinomas (5/50, 10%; 13/50, 26%; 17/50, 34%) and the combined incidence of hepatocellular adenomas and carcinomas (13/50, 26%, 23/50, 46%, 27/50, 54%) in male mice were statistically significant by the trend tests (P<0.01) and the incidences in the high-dose group were significantly higher than those in the controls (P<0.01). Metastases to the lung occurred in 1/50 control, 4/50 low-dose, 3/50 high-dose male mice. Fatty metamorphosis was found in increased incidence in the livers of dosed male mice (control 2/50; 16/50 low-dose; 15/50 high-dose).

Squamous cell papillomas were found in the stomach or forestomach in two high-dose females, one low-dose male, and one high-dose male. A squamous cell carcinoma was found in the forestomach of a third high-dose female. These tumors were probably related to administration of the test compound, since they are rarely observed in vehicle control and untreated control B6C3F₁ mice.

Under the conditions of this bioassay, bis (2-chloro-1-methylethyl) ether, containing 2-chloro-1-methylethyl (2-chloropropyl) ether, was carcinogenic for B6C3F₁ mice, causing increased incidences of alveolar/bronchiolar adenomas in male and females and hepatocellular carcinomas in males. In addition, the occurrence of a low incidence of squamous cell papillomas or carcinomas in the stomach or forestomach of females (a rare tumor in B6C3F₁ mice) was probably associated with the administration of bis(2-chloro-1-methylethyl)ether.

Synonyms for bis(2-chloro-1-methylethyl) ether: BCMEE; bis(2-chloroisopropyl) ether; BCPE

Note: Bis(2-chloro-1-methylethyl) ether was previously tested in F344 rats by gavage (See TR-191, reported 1979).

Report Date: December 1982

Target Organs & Incidences from 2-year Studies

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