Aniline cyanosis

As discussed in Section 3.1.1, groups of 10 8-w-old Crl CD rats were exposed to aniline vapor/aerosol at concentrations of 359, 400, 453, 530, or 786 ppm for 4 h (E.I.du Pont de Nemours 1982a). No deaths occurred at the lowest concentration. Signs at 359 ppm included cyanosis, tremors, lacrimation, salivation, semi-prostration, an initial body-weight loss followed by normal gain, and a reddish-brown perineal area. 

Kagan, B.M., B.Mirman, J.Calvin, and E.Lundeen. 1949. Cyanosis in premature infants due to aniline dye intoxication. J. Pediat. 34 574-578. 

Pickup, J.D., and J.Eeles. 1953. Cyanosis in newborn babies caused by aniline-dye poisoning. Lancet 2 118. 

Endpoint/Concentration/Rationale The only effect of aniline administration was formation of methemoglobin. Administration of 100 ppm for 8 h to rats resulted in elevation of methemoglobin to 22% but no hypoxic signs. A review of the literature revealed that methemoglobin levels of 15-20% in humans result in clinical cyanosis but no hypoxic symptoms. This effect was considered to be mild and reversible and, therefore, within the definition of the AEGL-1. The 8-h exposure to 100 ppm was chosen as the basis for the AEGL-1 calculations. 

Few reports of industrial experience are available from which to form an accurate appraisal of its health hazards it is said to be less potent than aniline as a cause of methemoglobin, but more of a central nervous system depressant. The effects of methemoglobinemia are cyanosis (especially of the lips, nose, and earlobes), weakness, dizziness, and severe headache. ... 

Percutaneous drug absorption can present special problems in newborns, especially in preterm infants. While the skin of a newborn term infant may have the same protective capacity as the skin of an adult, a preterm infant will not have this protective barrier until after 2 to 3 weeks of life. Excessive percutaneous absorption has caused significant toxicity to preterm babies. Absorption of hexachlorophene soap used to bathe newborns has resulted in brain damage and death. Aniline dyes on hospital linen have caused cyanosis secondary to methemoglobinemia, and EMLA (lidocaine/prilocaine) cream may cause methemoglobinemia when administered to infants less than 3 months of age. 

Aniline is extremely poisonous and if adsorbed through the skin may lead to cyanosis and death (Ref 5)... 

Nitrobenzene is a pale yellow oily liquid (mp, 5.7°C bp, 211°C) with an odor of bitter almonds or shoe polish. It is produced mainly for the manufacture of aniline. It can enter the body through all routes and has a toxicity rating of five. Its toxic action is much like that of aniline, including the conversion of hemoglobin to methemoglobin, which deprives tissue of oxygen. Cyanosis is a major symptom of nitrobenzene poisoning. 

Exposure to monochlorobenzene usually occurs by inhalation or skin contact. It is an irritant and affects the respiratory system, liver, skin, and eyes. Ingestion of this compound has caused incoordination, pallor, cyanosis, and eventual collapse, effects similar to those of aniline poisoning (see Section 15.3). Workers exposed to chlorobenzene have complained of headaches, numbness, sleepiness, and digestive symptoms, including nausea and vomiting. In general, most of these workers were exposed to other substances as well, so it is uncertain that their symptoms were due to chlorobenzene alone. 

Acrolein Ammonia Aniline (aminobenzene phenylamine) poisoning Lacrimation and respiratory irritation Eye irritation and pulmonary edema Cyanosis due to methemoglobinemia, slight narcosis, and respiratory paralysis... 

Its higher nitrated compds are powerful ezpls (see below). Military requirements of aniline are discussed in US Spec MIL-A-10450Aand its toxicity in Refs 4,7 11. Aniline is extremely poisonous and if adsorbed through the skin may lead to cyanosis and death (Ref 5)... 

SAFETY PROFILE A human poison by an unspecified route. Poison by ingestion and intravenous routes. Moderately toxic by intraperitoneal route. Human systemic effects by ingestion hallucinations and distorted perceptions, sleepiness, constipation, cyanosis, respiratory stimulation, kidney damage, methemoglobinemia-carboxyhemoglobinemia, and decreased body temperature. Mutation data reported. When heated to decomposition it emits toxic fumes of NOx. Combustible when exposed to heat or flame. See also ANILINE. 

SAFETY PROFILE Confirmed carcinogen. Poison by intravenous route. Moderately toxic by ingestion. This material, which so closely resembles aniline in the character of its toxic effects, is actually twice as toxic as aniline. It can cause injury to the blood and the liver. It does not necessarily give any alarm or warning, such as cyanosis, headache, and dizziness, which characterize antiine poisoning. Thus, it may be considered a more insidious poison than... 

Caution. Chloroform is a suspected carcinogen and may cause adverse reproductive effects. Aniline may cause cyanosis and may be fatal if absorbed... 

Nitrobenzene is toxic by all routes including skin absorption. Systemic effects may be delayed a few hours. Poisoning closely resembles aniline. Initial care should include adequate gastrointestinal (gastric lavage as indicated and activated charcoal) and dermal decontamination. The patient should be given oxygen and monitored for cyanosis. Cardiac rhythm should be monitored in symptomatic patients. 

A condition described as "hereditary methemoglobinemia" may result from a genetic defect (Goldstein et al. 1969). The enzyme methemoglobin reductase is absent and persons are hypersensitive to any substances such as nitrite or aniline derivatives capable of producing methemoglobinemia. The trait is inherited as an autosomal recessive allele. Thus either sex may exhibit the trait which is ordinarily detected by the presence of cyanosis at birth. Such individuals would be extremely sensitive to the effects of nitrobenzene. 

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