p-Phenylene diisothiocyanate

Odorless

Almost odorless

Colorless needles

Yellowish-white, crystalline powder

Practically insoluble in water. Sol in alcohol, chloroform.

Soluble in acetone and acetic acid

270 °F (EPA, 1998)

132 °C

132 °C

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P233, P260, P261, P264, P264+P265, P270, P271, P280, P284, P301+P316, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P351+P338, P305+P354+P338, P316, P319, P321, P330, P332+P317, P337+P317, P342+P316, P362+P364, P363, P403, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 44 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Benzene, 1,4-diisothiocyanato-: Does not have an individual approval but may be used under an appropriate group standard

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Bitoscanate is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500 or 10,000 lbs. Extremely hazardous substances that are solids are subject to either of two threshold planning quantities ... The lower quantity applies only if the solid exists in powdered form and has a particle size less than 100 microns; or is handled in solution or in molten form; or meets the criteria for a National Fire Protection Association (NFPA) rating of 2, 3 or 4 for reactivity. If the solid does not meet any of these criteria, it is subject to the upper ... threshold planning quantity ... .

Acute Tox. 3 (100%)

Reactive agents - 1st degree

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

1.8 [mg/m3]

20 [mg/m3]

25 [mg/m3]

For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)

EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration.

Exposure to high levels of cyanide for a short time harms the brain and heart and can even cause coma, seizures, apnea, cardiac arrest and death. Chronic inhalation of cyanide causes breathing difficulties, chest pain, vomiting, blood changes, headaches, and enlargement of the thyroid gland. Skin contact with cyanide salts can irritate and produce sores. (L96, L97)

Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (L97)

/LABORATORY ANIMALS: Acute Exposure/ Two cholangiotoxic agents, alpha-naphthylisothiocyanate (ANIT) and p-phenylenediisothiocyanate (PDT), were administered in single doses to mice to study their effects on the gallbladder. Both compounds caused maximal bile duct necrosis and periportal hepatocytic necrosis at 24 hr. The gallbladders were edematous but not necrotic at 24 hr after treatment. At 48 hr, and in some animals up to 4 days, severe cholecystitis was present, while bile ducts revealed progressive regeneration. The delay in the onset lesions gallbladder leions was probably the result of the toxic agent concentration in gallbladder bile after hepatic bile secretion was suppressed for 24 hr. The lesions provoked by PDT were similar to those induced by ANIT, except for a hemorrhagic component.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ 1,4-Phenylenediisothiocyanate was given to five groups of rats of different developmental stages (97 animals in all), and the changes in the hepatobiliary system were compared histopathologically. Three groups of rats given the drug after birth showed dilation of the extrahepatic bile ducts with inflammation. Two groups given the drug during the fetal period or added after birth showed stenotic or atretic extrahepatic bile ducts due to thickening and fibrosis of the wall. ...

LD50 Mouse ip 21 mg/kg

LD50 Mouse oral 230 mg/kg

LD50 Rat oral 21 mg/kg

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Bitoscanate is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500 or 10,000 lbs. Extremely hazardous substances that are solids are subject to either of two threshold planning quantities ... The lower quantity applies only if the solid exists in powdered form and has a particle size less than 100 microns; or is handled in solution or in molten form; or meets the criteria for a National Fire Protection Association (NFPA) rating of 2, 3 or 4 for reactivity. If the solid does not meet any of these criteria, it is subject to the upper ... threshold planning quantity ... .

Half-life of 0.5 and 8 days in renal elimination and fall-off of blood concentrations of half-life of 0.8 and 12 days /occurred after oral admin of bitoscanate to dogs/. /Similar results were obtained in man except that urinary excretion was more delayed, and more (14)C-bitoscanate was excreted renally/.

... a half-life of 26 days has been reported /in humans/.

Cyanide is rapidly alsorbed through oral, inhalation, and dermal routes and distributed throughout the body. Cyanide is mainly metabolized into thiocyanate by either rhodanese or 3-mercaptopyruvate sulfur transferase. Cyanide metabolites are excreted in the urine. (L96)

After oral administration of the anthelmintic, (14)C-bitoscanate to dogs, renal elimination ... and fall-off of blood concentrations ... of (14)C- were biphasic. Similar results were obtained in man except that urinary excretion was more delayed, and more (14)C- was excreted renally. Much of the (14)C- had been excreted within 5 days from both species, but excretion of the remainder was protracted. Thus after 3 weeks, the dog had excreted 80% in the feces, and 12% in the urine, and after 5 weeks, man had excreted respectively 55 and 28% by these routes; 3% still circulated in the blood. Fetuses contained 3% of the dose, 16 hr after admin of (14)C-bitoscanate to a pregnant dog. The data indicated that part of the (14)C binding to the tissues was only slowly excreted, possibly because (14)C-bitoscanate was irreversibly bound to biological macromolecules through its isothiocyanate groups. ... final rates of excretion of (14)C reflected rates of metabolism and excretion of the endogenous macromolecules to which bitoscanate was bound.

Bitoscanate is partly absorbed from the gastro-intestinal tract and slowly excreted ...

Anthelmintic

MEDICATION

Preparation and use as anthelmintic: FR M1652 and GB 1001314 (1963, 1965 to Hoechst).

Purification: Soeder, Laemmer, DE 1172664 (1964 to Hoechst).