2-Nitrophenylhydrazine

SECTION 2: Hazards identification

CHEMWATCH HAZARD RATINGS Min Max Flammability 2 Toxicity 2 Min/Nil=0 Body Contact 2 Low=1 Reactivity Moderate=2 2 High=3 Chronic 2 Extreme=4 CANADIAN WHMIS SYMBOLS EMERGENCY OVERVIEW RISK Heating may cause an explosion. Irritating to eyes, respiratory system and skin. Flammable. Harmful to aquatic organisms.

Potential Acute Health Effects

SWALLOWED ! Accidental ingestion of the material may be damaging to the health of the individual. ! The substance and/or its metabolites may bind to hemoglobin inhibiting normal uptake of oxygen. This condition, known as "methemoglobinemia", is a form of oxygen starvation (anoxia). ! Hydrazine (and some of its derivatives), is a strong convulsant in laboratory animals and can cause central nervous system (CNS) depression or stimulation. Symptoms of CNS depression may include nonspecific discomfort, giddiness, headache, dizziness, nausea, anaesthetic effects, slowed reaction time, slurred speech and may progress to unconsciousness. Serious poisonings may result in respiratory depression and may be fatal. CNS stimulation may produce dyspnea, coughing, bronchospasm, and laryngospasm. Muscular involvement may produce symptoms ranging from fasciculation to spasticity or seizures. Headache, dizziness and confusion may also result as can hyperpyrexia or a sensation of warmth. Other symptoms may include nausea, vomiting, diarrhoea and difficulty in urination. Cardiovascular involvement may produce alterations in blood pressure or arrhythmia. Pulmonary oedema and cardiovascular collapse also seem to be a feature of acute hydrazine poisonings. Animals that survive for more than a day frequently develop liver necrosis and renal failure. As judged by a few severe poisonings, man reacts like monkey in the sense that liver injury is more severe than kidney failure. Severe hypoglycaemia may develop even earlier than liver necrosis although this is rarely mentioned in the literature. EYE ! This material can cause eye irritation and damage in some persons. SKIN ! This material can cause inflammation of the skin oncontact in some persons. ! The material may accentuate any pre-existing dermatitis condition. ! Skin contact with the material may damage the health of the individual; systemic effects may result following absorption. ! Open cuts, abraded or irritated skin should not be exposed to this material. ! Entry into the blood-stream, through, for example, cuts, abrasions or lesions, may produce systemic injury with harmful effects. Examine the skin prior to the use of the material and ensure that any external damage is suitably protected. INHALED ! The material can cause respiratory irritation in some persons. The body's response to such irritation can cause further lung damage. ! Inhalation of dusts, generated by the material during the course of normal handling, may be damaging to the health of the individual. ! Persons with impaired respiratory function, airway diseases and conditions such as emphysema or chronic bronchitis, may incur further disability if excessive concentrations of particulate are inhaled. ! Symptoms of inhalation of hydrazine (and some of its derivatives), may include nausea and headache. Central nervous system (CNS) excitability may lead to convulsions and, in severe cases, respiratory arrest and death. Several instances of systemic poisoning, by hydrazine, have been reported in humans. These mainly involve the CNS, respiratory system and stomach. CNS stimulation may produce twitching of the extremities, clonic movements, hyperreflexia, convulsions and pyrexia; these may progress to lethargy, ataxia, confusion, coma and hypotension. Oliguria, haematuria, hyperglycaemia and/ or hypoglycaemia and elevated LFTs are common. Leucocytosis, parasthaesia and peripheral neuropathies may be delayed for several days. Respiratory (and dermal) exposure may produce deficits in concentration, comprehension, memory, task performance and mood status. Irritation of the mucous membranes may produce rhinitis, salivation, coughing, choking and dyspnoea.

Potential chronic health

! Long-term exposure to respiratory irritants may result in disease of the airways involving difficult breathing and related systemic problems. There has been some concern that this material can cause cancer or mutations but there is not enough data to make an assessment. Limited evidence suggests that repeated or long-term occupational exposure may produce cumulative health effects involving organs or biochemical systems. There is some evidence that inhaling this product is more likely to cause a sensitization reaction in some persons compared to the general population. Phenylhydrazines are capable of exerting haemolytic effects following a haemoglobin-catalysed metabolic conversion. This haemolytic effect is a consequence of the formation of free radicals in which phenylhydrazine undergoes oxidation to a phenyl diazinyl radical intermediate and subsequent conversion to a phenyl radical (and nitrogen, N2). Oxygen activation (generation of a superoxide) occurs during one of the reactions of this metabolic sequence. Superoxide is a strong base and can therefore attract protons from a variety of compounds; it is also a potent reducing agent which can reduce transition metal ions (such as Fe3+ and Cu+) to their reduced form Superoxide may also act as a nucleophile and may readily react with a number of electrophilic agents. Finally superoxide may initiate oxidation reactions, for example, of molecules such as ascorbic acid or epinephrine (adrenaline) following hydrogen abstraction due to its basicity. Under certain conditions the rate of formation of reactive oxygen species may exceed the capacity of the bodies auto-oxidative defence mechanisms and, as a result, result in "oxidative stress'". Oxidative stress appears to be involved in some biological processes such as aging and inflammation reactions and is thought to play a role in the pathogenesis of several diseases, including acute pancreatitis, post-ischaemic syndrome,tumour formation, atherosclerosis and diabetic angiopathy. Free radicals can react with specific cellular molecules including low molecular weight biomolecules such as neurotransmitters and co-enzymes and, as a consequence, inactivate them. macromolecules and cellular membranes are particularly vulnerable to free radical damage with the resultant loss of physiological function and cell death Depolymerisation of polysaccharides (such as hyaluronic acid) may result in inflammation of the joints. Free radicals have a high affinity for sulfur containing amino-acids and therefore many proteins. The may bind covalently to these proteins leading to loss, of biological function such as catalysis exhibited by enzymes. Covalent binding may also result in allergic reactions when the modified protein is recognised, by the bodies immune system, as "foreign" Free radicals are also capable of causing proteins to cross-link to yield larger aggregates. Free radicals are also able to react with the nucleic acids of DNA which may affect cell division or cell death Oxidative modifications of DNA may result in tumour initiation. Lipids containing several double bonds (such as polyunsaturated fatty acids and cholesterol) are also subject to damage. In the case of membrane phospholipids, such "peroxidation" results in impairment of cellular and/ or subcellular membranes which may produce cell death. Transition metal ions may also play an important role in lipid peroxidation after free radical-induced change of valency . Fe3+/Fe2+, copper and mercury ions, as well as vanadate and chromate ions seem to initiate this process and may even exacerbate it by producing secondary radicals when the phospholipid is modified. When administered orally, hydrazine induced pulmonary adenomas and adenocarcinomas in mice. Inhalation induced lung carcinomas and lymphosarcomas of the spleen in female mice. A study of 423 men, involved in the manufacture of hydrazine revealed three stomach, one prostate and a neurogenic cancer. Chronic exposure to phenylhydrazine can cause damage to the liver, lungs and kidneys. Rats receiving 0.25 to 0.5 mg phenylhydrazine/animal/day,, 5 days/week for 40 weeks by gavage exhibited haemolytic anaemia. Mice given 1 mg phenylhydrazine orally/mouse/day, 7 days/week for 42 weeks showed an increase incidence of total and malignant lung tumours. Another study with the hydrochloride in drinking water (average 0.63 to 0.81 mg/day) over their lifetime showed an increase in blood vessel tumours. When phenylhydrazine was given orally to mice (5 days/week for 40 weeks 0.25 mg-0.5 mg) no significant carcinogenic response was seen. The mechanism of carcinogenic activity displayed by hydrazine may include indirect alkylation of DNA which is closely related to the toxic endpoint.