Gallium nitrate

Danger

H272 (100%): May intensify fire; oxidizer [Danger Oxidizing liquids; Oxidizing solids]；H314 (10%): Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]；H315 (90%): Causes skin irritation [Warning Skin corrosion/irritation]；H319 (90%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]；H335 (10%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

P210, P220, P260, P261, P264, P264+P265, P271, P280, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P351+P338, P305+P354+P338, P316, P319, P321, P332+P317, P337+P317, P362+P364, P363, P370+P378, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 10 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

SYMPTOMS: Symptoms of exposure to this compound include nausea, vomiting, renal function depression, proteinuria, normocytic anemia and thrombocytopenia.；ACUTE/CHRONIC HAZARDS: This compound is irritating to the skin. It emits toxic fumes when heated to decomposition. (NTP, 1992)

Oxidizing agents, such as GALLIUM NITRATE, can react with reducing agents to generate heat and products that may be gaseous (causing pressurization of closed containers). The products may themselves be capable of further reactions (such as combustion in the air). The chemical reduction of materials in this group can be rapid or even explosive, but often requires initiation (heat, spark, catalyst, addition of a solvent). Explosive mixtures of inorganic oxidizing agents with reducing agents often persist unchanged for long periods if initiation is prevented. Such systems are typically mixtures of solids, but may involve any combination of physical states. Some inorganic oxidizing agents are salts of metals that are soluble in water; dissolution dilutes but does not nullify the oxidizing power of such materials. Organic compounds, in general, have some reducing power and can in principle react with compounds in this class. Actual reactivity varies greatly with the identity of the organic compound. Inorganic oxidizing agents can react violently with active metals, cyanides, esters, and thiocyanates.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.；SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.；INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.；INGESTION: Some heavy metals are VERY TOXIC POISONS, especially if their salts are very soluble in water (e.g., lead, chromium, mercury, bismuth, osmium, and arsenic). IMMEDIATELY call a hospital or poison control center and locate activated charcoal, egg whites, or milk in case the medical advisor recommends administering one of them. Also locate Ipecac syrup or a glass of salt water in case the medical advisor recommends inducing vomiting. Usually, this is NOT RECOMMENDED outside of a physician's care. If advice from a physician is not readily available and the victim is conscious and not convulsing, give the victim a glass of activated charcoal slurry in water or, if this is not available, a glass of milk, or beaten egg whites and IMMEDIATELY transport victim to a hospital. If the victim is convulsing or unconscious, do not give anything by mouth, assure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.；STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

Excerpt from ERG Guide 140 [Oxidizers]:；IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.；LARGE SPILL: Consider initial downwind evacuation for at least 100 meters (330 feet).；FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. If ammonium nitrate products are in a tank, rail car or truck and involved in a fire, ISOLATE for 1600 meters (1 mile) in all directions; also, initiate evacuation including emergency responders for 1600 meters (1 mile) in all directions. (ERG, 2024)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Drug Induced Liver Injury Rank (DILIrank 2.0)

Gallium nitrate

Ambiguous-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

Gallium nitrate produces a hypocalcemic effect by inhibiting calcium resorption from bone, possibly blocking osteoclast activity and reducing increased bone turnover. Preclinical studies demonstrated that gallium dose-dependently accumulates in areas of high bone turnover, where it is incorporated into hydroxyapatite, making it less susceptible to dissolution and osteoclast-mediated resorption. No cytotoxic effects were observed on bone cells in drug-treated animals. Gallium nitrate exhibits antitumour activity, which is reported to be unrelated to the physiological mechanism involved in its bone turnover effects. Anti-inflammatory and immunosuppressant effects have also been documented.

A high incidence of hypercalcemia is often observed in patients with non-small cell lung cancer, breast cancer, multiple myeloma, kidney cancer, and cancer of head and neck. Hypercalcemia of malignancy seems to result from an imbalance between the net resorption of bone and urinary excretion of calcium. Patients with extensive osteolytic bone metastases frequently develop hypercalcemia. Although _in vitro_ and animal studies have been performed to investigate the mechanism of action of gallium nitrate, the precise mechanism for inhibiting calcium resorption has not been determined. Gallium, the active component that exerts the physiological effects of gallium nitrate, may induce physicochemical changes in the bone matrix to promote hydroxyapatite crystallization and attenuate mineral dissolution. Gallium may also decrease acid secretion by osteoclasts and modulate the synthesis of osteocalcin, an osteoblast-specific bone matrix protein that triggers bone resorption. Osteoclast morphology or viability is not reported to be affected. Gallium nitrate may modulate inflammation. _In vitro_, it was shown to block the production of inflammatory cytokines, such as interleukin-1 (IL-1) beta, by macrophage-like cells. Gallium nitrate also dose-dependently inhibited matrix metalloproteinase activity promoted by tissue plasminogen activator (tPA).

In phase I studies involving cancer patients who received a short-term intravenous infusion of single doses ranging from 300 to 900 mg/m², a biphasic curve was observed. Gallium nitrate exhibited a mean initial (distribution phase) half-life of 1 to 1.5 hours and a terminal (elimination phase) half-lives of 25 to 30 hours.

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GALLIUM NITRATE ANHYDROUS

Physiologic Effects [PE] - Bone Resorption Inhibition

Established Pharmacologic Class [EPC] - Calcium Resorption Inhibitor

Gallium nitrate anhydrous is a Calcium Resorption Inhibitor. The physiologic effect of gallium nitrate anhydrous is by means of Bone Resorption Inhibition.

Substances that inhibit or prevent the proliferation of NEOPLASMS.

Hormones and molecules with calcium-regulating hormone-like actions that modulate OSTEOLYSIS and other extra-skeletal activities to maintain calcium homeostasis.

Gallium nitrate was infused at a daily dose of 200 mg/m2 for 5 (n=2) or 7 (n=10) consecutive days to 12 cancer patients. In most patients, mean steady-state plasma concentrations were reached after 18 to 24 hours of infusion. The average steady-state plasma levels of gallium observed among seven fully evaluable patients was between 1134 and 2399 ng/mL. In one patient who received daily infusion doses of 100, 150 and 200 mg/m2, the apparent steady-state levels of gallium did not increase proportionally with an increase in dose.

Gallium nitrate appears to be significantly excreted via the kidney. In phase I studies involving cancer patients who received a short-term intravenous infusion of single doses ranging from 300 to 900 mg/m², about two-thirds of the administered dose was recovered in the urine in the first 24 hours post-dose.

In phase I studies involving cancer patients who received a short-term intravenous infusion of single doses ranging from 300 to 900 mg/m², the mean volume of distribution of gallium was 1.27 L/kg.

In cancer patients who received a daily infusion of gallium nitrate at a dose of 200 mg/m² for five to seven consecutive days, the average plasma clearance of gallium was 0.15 L/hr/kg (range: 0.12 to 0.20 L/hr/kg).