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No data available for the determination of toxicokinetics, metabolism and distribution. In general it is stated that the formation of nitrosamines from nitrite and diethylamine depends greatly on the basicity of the amines.

 

Assessment of Toxicokinetic Behaviour

Diethylamine (Cas-No. 109-89-7) is a colourless liquid with a molecular weight of 73.1 g/mol and a vapour pressure of 316 hPa (25°C). It is completely miscible at 25 °C in water, the log Po/w is 0.58.

 

Evidence for systemic availability of Diethylamine comes from acute (oral, dermal, inhalation), subacute and sub-chronic studies.

 

In a oral toxicity study a LD50= 540 mg/kg bw (20%) (Smyth 1951) and a LD50: > 710 mg/kg bw (10%) (Union Carbide 1979) was determined. Main clinical signs observed were sluggishness, gasping and reduced body temperature. At necropsy, congestion of the lungs, liver and kidney, and in the stomachs and intestines were observed.However, the fact that undiluted test substance (a corrosive substance) was ingested and its subsequent corrosive (as indicated by distended, liquid filled, red and walls thickened stomachs, which were ulcerated and adhered to surrounding tissue) may have secondary lead to death of treated animals.

In an inhalation study a LC50 was set to be 5700 ppm (17.3 mg/l air) (Union Carbide 1979). Irritation of the extremities, respiratory distress and loss of coordination were observed during exposure to this concentration and to 4000 ppm. Gross necropsy revealed red lungs and yellowish, gas- and liquid-filled intestines. Additional data were available from an inhalation risk test (IRT) (BASF AG, 1955). The inhalation of a saturated vapor-air mixture for 1 min caused mortality. Clinical signs were convulsions, lateral position, twitching, and dyspnoea. At necropsy, pulmonary hyperemia was observed.

Dermal toxicity of rabbit skin, LD50: 582 mg/kg bw (Smyth 1951). In a second study LD50: 628 mg/kg bw (Myers 1997). In both studies the substance caused local effects like hemorrhage and necrosis of the skin and underlying muscular layers. As systemic effect loss of coordination was observed. At gross necropsy examination mottled surfaces of the livers and kidneys, and congested or hemorrhagic intestines were noted. Spleens were darkened to the point of being called black, pancreas congested and testes hemorrhagic.

 

Taken together, Diethylamine resulted in mortality after inhalative, dermal and oral exposure. In all three cases the primary effect was the local effect.

 

 

In the 2-week studies rats and mice were exposed to Diethylamine vapor at concentrations of 0, 31, 62.5, 125, 250, or 500 ppm. All rats survived to the end of the study but two male and three female mice exposed to 500 ppm died during the first week of the study. The mean body weights of rats and mice exposed to 125 ppm or greater were significantly less than those of the chamber controls. Clinical findings included lethargy, nasal/eye discharge, abnormal breathing, thinness, eye abnormalities, and discolored urine. The thymus weights of male rats exposed to 125 ppm or greater and female rats exposed to 500 ppm and male mice of 250 and 500 ppm and females of 125 ppm or greater were significantly less than those of the chamber controls. Histopathological changes were noted primarily in the nasal cavity and involved both the respiratory and olfactory epithelium of males and females principally in the 125, 250 or 500 ppm groups. These lesions included suppurative inflammation, squamous metaplasia of the respiratory epithelium, olfactory epithelial atrophy, and necrosis of the turbinates.

 

In the 90 day study rats and mice were exposed to Diethylamine vapor at concentrations of 0, 8, 16, 32, 62, or 125 ppm. All animals survived to the end of the study. The mean body weights of 125 ppm rats were significantly less than those of the chamber controls. There was significant exposure concentration-related decreases in sperm motility in male rat and mice exposed to 32, 62, or 125 ppm; the estrous cycle of 125 ppm mice was significantly longer than that of the chamber controls but only by half a day. Histopathological changes were noted primarily in the nasal cavity and involved both the respiratory and olfactory epithelium of males and females principally in the 62 or 125 ppm groups. These lesions included suppurative inflammation, squamous metaplasia of the respiratory epithelium, olfactory epithelial atrophy, and necrosis of the turbinates.

A transient reduction in growth and histopathologic changes of the nares occurred in rats exposed to 250 ppm for 6.5 hr/day, 5 days/wk for 6 months (Lynch, 1986; reliability score: 2). No effects were seen on organ weights or on the blood, and microscopic examination of the tissues of the major organs did not reveal any abnormalities that could be related to treatment. There were no signs of toxicity in rats exposed to 25 ppm (75 mg/m³) under the same conditions.

 

As already indicated by the acute toxicity data, the existing repeated dose toxicity data (inhalative route of exposure) indicate that the local effects (respiratory tract) are the primary effects of Diethylamine.