Vincaleukoblastine, sulfate (1 1) (salt)

SECTION 2: Hazards identification

Appearance: White to off-white powder Physical State: Solid Odor: Odorless Emergency Overview Special R = Reproductive Emergency Overview Effective Date: 18-May-2000 Lilly Laboratory Labeling Codes: Health 3 Fire 1 Reactivity 1 Special R Primary Physical and Health Hazards: Highly Toxic. Corrosive (eyes). Irritant (skin, respiratory tract). Reproductive, Blood and Bone Marrow Effects. Caution Statement: Vinblastine Sulfate for Injection is highly toxic, may cause burns or permanent tissue damage to the eyes, and may be irritating to the skin and respiratory tract. Effects of exposure may include decreased fertility, fetal changes, changes in blood cell counts, and bone marrow changes.

Principle Routes of Exposure

Inhalation and skin contact Effects of Overexposure: Vinblastine sulfate's major anti-tumor activity, when administered to patients intravenously, is to arrest cell mitosis. It has subtle effects of nucleic acid synthesis, but not on nucleic acid function. In the manufacturing setting, vinblastine sulfate powder and vinblastine sulfate have been reported to be skin irritants. Black workers have experienced depigmentation. Accidental contamination of the eye in the manufacturing setting and in clinical settings results in severe irritation, tearing, pain, and blurred vision. Healing occurs within two weeks without loss of vision. In laboratory animals, "pitting" of the cornea has occured after direct application of vinblastine to the eye. Pitting may be delayed, but can heal without loss of vision. If delivered under pressure, corneal ulceration has occured in these animals. NOTE TO PHYSICIAN: Vinca alkaloids do not cause a direct chemical burn of eye tissue, but interfere with the reproduction of the corneal epithelium, which occurs continuously. The result is a delayed burn and subsequent scarring. While very painful, all cases have recovered completely without any loss of eye function. Some patients treated with combination therapy which included vinblastine sulfate have developed second malignancies. The available data are insufficient to evaluate the mutagenic or chromosomal effects of vinblastine sulfate in humans. Some patients treated with combination therapy which included vinblastine sulfate have had a decrease in fertility. Vinblastine sulfate is embryotoxic and teratogenic in animals. There have been no clinical trials in humans to determine if vinblastine sulfate causes malformations of the human fetus. Information on the use of vinblastine sulfate during human pregnancy is limited. There are individual case reports of normal infants born to patients treated with vinblastine sulfate therapy alone for malignant disease throughout pregnancy. There are individual case reports of abnormal infants born to patients treated in the first trimester with combination therapy which included vinblastine. There have been no studies to determine whether immune suppression occurs in workers handling vinblastine sulfate. The major adverse effect in patients receiving intravenous doses of vinblastine sulfate relates to reduced production of cells by the bone marrow. No inhalation studies have been done on animals or humans. Inhalation of a sufficient amount of vinblastine powder or vinblastine sulfate powder would be expected to cause local irritation of the nose and throat. Vinblastine sulfate is not dependably absorbed after oral administration to patients. The systemic effect of accidental or intentional ingestion or inhalation would be variable, depending upon the amount absorbed. Hospital employees and health care providers who prepare many cytostatic drugs in an unprotected environment have been reported to have increased levels of mutagens in their urine. The significance of this finding is not known.

Medical Conditions Generally Aggravated by Exposure

None known Carcinogenicity: IARC Group 3 (not classifiable as to human carcinogenicity). Not listed by NTP, ACGIH, or OSHA.