Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION

PRODUCT NAME

HERBIMYCIN A

NFPA

PRODUCT USE

Antibiotic produced by the actinomycetes organism Streptomyces hygroscopicus with
antiparasite and antineoplastic properties. Inhibitor of tyrosine kinase. Also inhibits
platelet derived growth factor induced phospholipase D activation. Angiogenesis inhibitor.
Has potent herbicidal activity against most mono- and di- cotyledenous plants, especally
against Cyperus microiria STEUD. Oryza sativa shows strong resistance to herbimycin.

SYNONYMS

C30-H42-N2-O9, "geldanamycin, 17-demethoxy-15-methoxy-11-O-methyl-, (15R)-",
"geldanamycin, 17-demethoxy-15-methoxy-11-O-methyl-, (15R)-", "Antibiotic TAN 420F", "2-
azabicyclo[16.3.1]docasa-4, 6, 10, 18, 21-pentaene-3, 20, 22-trione, 9, 13-dihydroxy-8,
14, 15-trimethoxy-4, 10, 12, 16-tetramethyl-11-O-methyl-9-carbamate", "2-
azabicyclo[16.3.1]docasa-4, 6, 10, 18, 21-pentaene-3, 20, 22-trione, 9, 13-dihydroxy-8,
14, 15-trimethoxy-4, 10, 12, 16-tetramethyl-11-O-methyl-9-carbamate", "[(18S-(4E, 5Z, 8R*,
9R*, 10E, 12R*, 13S*, 14R*, 16S*)]-9-[(aminocarbonyl)oxy]-13-hydroxy-8, 14, 15-trimethoxy-
4, 10, 12, 16-tetramethyl-2-azabicyclo[16.3.1]-docosa-11-O-methyl-4, 6, 10, 18, 21-pentan-
3, 20, 22-trione", "[(18S-(4E, 5Z, 8R*, 9R*, 10E, 12R*, 13S*, 14R*, 16S*)]-9-
[(aminocarbonyl)oxy]-13-hydroxy-8, 14, 15-trimethoxy-4, 10, 12, 16-tetramethyl-2-
azabicyclo[16.3.1]-docosa-11-O-methyl-4, 6, 10, 18, 21-pentan-3, 20, 22-trione",
"tyrosine kinase inhibitor", "antibiotic/ chemotherapeutic/ antineoplastic/ cytotoxic/
herbicide/pesticide"

Section 2 - HAZARDS IDENTIFICATION

CANADIAN WHMIS SYMBOLS

EMERGENCY OVERVIEW

RISK

Harmful by inhalation, in contact with skin and if swallowed.
Irritating to eyes, respiratory system and skin.

POTENTIAL HEALTH EFFECTS

ACUTE HEALTH EFFECTS

SWALLOWED

  Accidental ingestion of the material may be harmful; animal experiments indicate that ingestion of less than 150 gram may be fatal or may produce serious damage to the health of the individual.  Harmful if swallowed.  At sufficiently high doses the material may be neurotoxic(i.e. poisonous to the nervous system).  Side-effects for rifampicin and its congeners, include severe gastrointestinal disturbance, abnormalities in liver function, (jaundice and hepatitis), febrile reaction with influenza-like symptoms, confusion, drowsiness, weakness, ataxia, dizziness, peripheral neuropathy, blurred vision, transient hearing loss and menstrual irregularities. Alterations to kidney function and liver failure may be due to hypersensitivity with skin reaction, eosinophilia, leukopenia, thrombocytopenia, purpura, haemolysis and shock further emphasising such reaction.  The killing action of antineoplastic drugs used for cancer chemotherapy is not selective for cancerous cells alone but affect all dividing cells. Acute side effects include loss of appetite, nausea and vomiting, allergic reaction (skin rash, itch, redness, low blood pressure, unwellness and anaphylactic shock) and local irritation. Gout and renal failure can occur.  

EYE

  This material can cause eye irritation and damage in some persons.  Irritating to eyes.  The dust may produce eye discomfort causing smarting, pain and redness.  

SKIN

  Skin contact with the material may be harmful; systemic effects may resultfollowing absorption.  This material can cause inflammation of the skin oncontact in some persons.  Harmful in contact with skin.  Irritating to skin.  Open cuts, abraded or irritated skin should not be exposed to this material.  

INHALED

  If inhaled, this material can irritate the throat andlungs of some persons.  Harmful by inhalation.  Irritating to respiratory system.  Respiratory sensitization may result in allergic/asthma like responses; from coughing and minor breathing difficulties to bronchitis with wheezing, gasping.  

CHRONIC HEALTH EFFECTS

  There is some evidence that inhaling this product is more likely to cause a sensitization reaction in some persons compared to the general population.  

  May cause birth defects.  May cause birth defects.  There is limited evidence showing the congener, geldanamycin,  is teratogenic and tumorigenic in laboratory animals.  Exposure to small quantities may induce hypersensitivity reactions characterized by acute bronchospasm, hives (urticaria), deep dermal wheals (angioneurotic edema), running nose (rhinitis) and blurred vision . Anaphylactic shock and skin rash (non-thrombocytopenic purpura) may occur. An individual may be predisposed to such anti-body mediated reaction if other chemical agents have caused prior sensitization (cross-sensitivity).  Anti-cancer drugs used for chemotherapy can depress the bone marrow with reduction in the number of white blood cells and platelets and bleeding. Susceptibility to infections and bleeding is increased, which can be life- threatening. Digestive system effects may include inflammation of the mouth cavity, mouth ulcers, esophagus inflammation, abdominal pain and bleeds, diarrhea, bowel ulcers and perforation. Reversible hair loss can result and wound healing may be delayed. Long-term effects on the gonads may cause periods to stop and inhibit sperm production. Most anti-cancer drugs can potentially cause mutations and birth defects, and coupled with the effects of the suppression of the immune system, may also cause cancer.  The material may inhibit protein kinase. This family of kinases enzymatically catalyses the phosphorylation of protein . Because phosphorylation triggers a signaling cascade which in turn produces cell growth, inhibition effectively retards the process. There are several different inhibitors which act in this manner but most common are genistein (a naturally occurring steroid-like substance from soybeans), lavendustin (a microbial metabolite) and the tyrphostins (synthetic analogues).  Two families of protein kinase have been identified;  · serine-threonine kinases (also known as PKC) require calcium ion for their activation. The activated PKC phosphorylates proteins of the cellular signal cascade, which eventually induce expression of growth regulatory genes.  · tyrosine kinases which similarly regulate signal transmission to growth regulatory genes  Inhibition may suppress cell or tissue growth or development.