Acute vapour inhalation toxicity of acrolein and its influence as a trace contaminant in 2-methoxy-3,4-dihydro-2H-pyran.

1. The LC50 values for acrolein (AC) vapour to Sprague-Dawley rats (combined sexes) were determined to be 26 ppm (1 h) and 8.3 ppm (4 h). Signs of severe irritancy were present, and death was due to lung injury. 2. Exposure of rats to a 2-methoxy-3,4-dihydro-2H-pyran (MDP) saturated vapour atmosphere statistically generated from liquid MDP containing 0.037% AC, caused severe irritancy and death from accumulation of AC vapour. Sparging the impure material with nitrogen gas before atmosphere generation significantly reduced or abolished lethal toxicity. 3. Dynamically generated MDP vapour atmosphere produced transient respiratory and ocular irritancy, but no mortalities. The intrinsic acute vapour inhalation toxicity of MDP is low. 4. The presence of highly volatile toxic impurities in a material may confer a significant acute inhalation toxicity and hazard under conditions of low air movement. Assessment of potential inhalation hazards from liquid mixtures may require investigation by static and dynamic methods for vapour generation.

The acute toxicity of tris(dimethylamino)silane.

The acute handling hazards of tris(dimethylamino)silane [TDMAS] were investigated. The acute male rat peroral LD50 (with 95% confidence limits) was 0.71 (0.51-0.97) ml/kg, and the acute male rabbit percutaneous LD50 was 0.57 (0.35-0.92) ml/kg. The liquid was severely irritating to the rabbit eye and skin, and the vapor severely irritating to the rat eye. The dynamically generated saturated vapor Lt50 in female rats was 12 (9.7-15) min. The effect of varying the atmospheric concentration of vapor from TDMAS on acute inhalation toxicity was investigated by passing ordinary moist air countercurrent to liquid TDMAS metered into a slightly heated glass tube. Based on nominal concentrations, the 4 hr-LC50 for vapor from TDMAS was 734 (603-893) ppm in female rats by this procedure. Stoichiometrically, this accords with toxicity due to liberation of dimethylamine (DMA) from TDMAS. In a subsequent study designed to assess the influence of relative humidity on vapor toxicity, nitrogen was passed over heated liquid TDMAS and the resultant atmosphere was introduced into the air intake duct of the inhalation exposure chamber. Gas chromatographically measured TDMAS concentrations (+/- SD) were 395 +/- 111, 127 +/- 25, 62 +/- 8 and 23 +/- 21 ppm; the corresponding DMA vapor concentrations were 112 +/- 171, 31 +/- 43, 10 +/- 6 and 26 +/- 44 ppm. The 4-hr LC50 (males and females) was 38 (34-43) ppm TDMAS vapor. Thus, TDMAS is of moderate acute peroral and percutaneous toxicity, a severe primary skin and eye irritant, an aspiration hazard, and of high intrinsic acute inhalation toxicity, but in moist air conditions lethal toxicity may be reduced and in such circumstances DMA may be a significant factor in toxicity.

Acute toxicity and primary irritation of para-tertiary butylphenol.

Para-tertiary butylphenol [(PTBP); the Union Carbide Corporation trademark for this chemical is UCAR Butylphenol 4-T Flake] has applications as a raw material in the manufacture of resins and also as an industrial intermediate. Acute peroral LD50 values (95% confidence limits) of 5.4 (3.6-7.9) g/kg and 3.6 (3.0-4.4) g/kg were obtained for male and female albino rats, respectively. Occluded cutaneous applications of moistened PTBP at 16 g/kg for 24 hr produced no mortalities in male or female rabbits, but signs of local toxicity and irritation were apparent at the site of application. A 6 hr exposure to a substantially saturated vapor under static conditions produced no mortality, while a 4 hr exposure to a dynamically generated respirable dust aerosol at a concentration of 5.6 mg/L produced 20% mortality. Occluded dermal contact (4 hr) with 0.5 g moistened PTBP produced a range of effects from no reaction to necrosis. PTBP placed in the conjunctival sac of rabbits produced severe ocular injury which generally persisted for 21 days after exposure. The major hazard associated with acute exposure to PTBP appears to be the irritation produced by dermal or ocular contact.

Acute and 2-week inhalation toxicity studies on aerosols of selected ethylene oxide/propylene oxide polymers in rats.

The ethylene oxide/propylene oxide (EO/PO) polymers evaluated in this study have previously been shown to have a low order of toxicity and/or irritancy by ocular, dermal, or oral routes of administration. These studies evaluated the acute inhalation toxicity of respirable aerosols of three EO/PO compounds (U-660, U-2000, and U-5100) that differ in chain length, molecular weight, and viscosity. The respective 4-hr LC50 values (95% confidence limits) for U-660, U-2000, and U-5100 in Wistar albino rats were 4670 (4090-5320), 330 (227-480), and 106 (45-245) mg/m3. Occasionally, slight increases in respiration rate and slight hyperactivity were observed during the postexposure period. All deaths were delayed for 2-5 days postexposure. Body weight gains were transiently depressed in rats exposed to U-2000 and U-5100. Discolored lungs and livers occurred in animals which died during the 14-day postexposure period. Subsequently, a repeated-exposure study was conducted on U-5100 in F-344 rats exposed for 6 hr/day, 5 days/week, for 9 exposures at mean concentrations of 0, 5, 26, and 50 mg/m3. Portions of the control and 50 mg/m3 groups were maintained for an additional 2-week recovery period. Exposure-related effects included transient urogenital wetness in 50 mg/m3 group females; decreased body weight gain (7-29%) in all U-5100 groups except the 5 mg/m3 group females; increases in absolute (17-52%) and relative lung weights in all U-5100 groups; macroscopic red foci in the lungs; and microscopic findings of congestion and hemorrhage of pulmonary alveolar capillaries and necrosis of alveolar epithelial cells. Lung weights remained elevated after the 2-week recovery period, but the severity of the microscopic lesions was noticeably less, indicating partial reversibility of the lesions. In conclusion, EO/PO polymers have a higher order of toxicity by inhalation in comparison to other routes of administration, vary considerably in their acute lethal toxicity as a function of chain length/molecular weight, and induce pulmonary hemorrhage, and possibly edema, following repeated aerosol exposures at concentrations as low as 5 mg/m3.

Dimethylethanolamine: acute, 2-week, and 13-week inhalation toxicity studies in rats.

Dimethylethanolamine (DMEA) is a volatile, water-soluble amine that has applications in the chemical and pharmaceutical industries. These studies evaluated the acute and subchronic inhalation toxicity of DMEA. Acute (4-hr) exposures of Wistar rats to DMEA vapor resulted in an LC50 value (95% confidence limits) of 1641 (862-3125) ppm. Clinical signs of nasal and ocular irritation, respiratory distress, and body weight loss were observed in rats exposed to 1668 ppm DMEA and higher. In the 2-week study, F-344 rats exposed to 98, 288, or 586 ppm DMEA for 9 days (6 hr/day) during an 11-day period also exhibited signs of respiratory and ocular irritation (except the 98 ppm group). All animals of the 586 ppm group and 4 of 15 male rats of the 288 ppm group died. Body weight values for the 288 ppm group were reduced to about 75% of preexposure values, while the 98 ppm group gained 35% less weight than controls. Statistically significant differences in clinical pathology parameters (288 ppm group) and in organ weight values (288 and 98 ppm groups) probably resulted from the decreased food consumption and not from specific target organ toxicity. In the groups evaluated histologically (the 98 and 288 ppm groups) the eye and nasal mucosa were the primary target organs. In the 13-week subchronic study, F-344 rats were exposed to 0, 8, 24, or 76 ppm DMEA for 6 hr/day, 5 days/week for 13 weeks. The principal exposure-related changes were transient corneal opacity in the 24 and 76 ppm groups; decreased body weight gain for the 76 ppm group; and histopathologic lesions of the respiratory and olfactory epithelium of the anterior nasal cavity of the 76 ppm group and of the eye of several 76 ppm group females. Rats maintained for a 5-week recovery period only exhibited histological lesions of the nasal tissue, with the lesions being decreased in incidence and severity. DMEA acts primarily as an ocular and upper respiratory tract irritant and toxicant at vapor concentrations of 76 ppm, while 24 ppm or less produced no biologically significant toxicity in rats. Thus, 24 ppm was considered to be the no-observable-effect level.

Acute, 9-day, and 13-week vapor inhalation studies on ethylene glycol monohexyl ether.

At ambient conditions, the low vapor pressure of ethylene glycol monohexyl ether (EGHE) allows for a maximum vapor concentration of approximately 85 ppm. In an acute inhalation study on Wistar albino rats, a 4-hr exposure to 83 ppm EGHE produced no clinical signs, body weight effects, mortality, or macroscopic lesions in thoracic or abdominal organs. Fischer 344 rats exposed for 9 days (6 hr/day) over an 11-day period, to 0 (control), 19, 41, or 84 ppm EGHE had decreased body weight gains and increased liver to body weight values at 84 ppm EGHE. No alterations of the hematology parameters or the morphology of the testes or liver were observed. In a subsequent study, rats were exposed to mean EGHE concentrations of 0 (control), 20, 41, or 71 ppm for 6 hr/day, 5 days/week, for 13 weeks. Urogenital wetness was observed in all EGHE-exposed groups of females and in males of the 71-ppm group. Decreased body weight gains were observed in both sexes of the 71-ppm group, and a slight decrease was also observed in females of the 41-ppm group. Increased absolute and/or relative liver weights were observed in both sexes of the 71-ppm group and to a lesser extent in the 41-ppm group. Possibly related to these findings in the liver were decreases in serum transaminases (aspartate and alanine aminotransferase) and sorbitol dehydrogenase, with an increase in alkaline phosphatase observed in the 71-ppm group of female rats. However, there were no gross or histopathologic lesions found to indicate impairment of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

The acute toxicity and primary irritancy of 2,4-pentanedione.

2,4-Pentanedione was found to have acute peroral LD50 values (with 95% confidence limits) in the rat of 0.78 (0.66-0.91) ml/kg for males and 0.59 (0.51-0.70) ml/kg for females, and acute percutaneous LD50 values by 24 hr occluded contact on the rabbit of 1.41 (0.80-2.49) ml/kg for males and 0.81 (0.59-1.12) for females. Lt50 values for exposure of rats to saturated vapor atmospheres were 52 min (7060 ppm) for males and 55 min (7912 ppm) for females. The 4 hr LC50 value for rats was 1224 (1063-1409) ppm for combined male and female data. A 4 hr occluded contact with 0.5 ml produced mild local erythema and edema. Instillation of 0.1 ml into the inferior conjunctival sac, produced mild conjunctivitis of less than 24 hr duration without corneal injury.

The acute toxicity and primary irritancy of 2-ethyl-1,3-hexanediol.

2-Ethyl-1,3-hexanediol (EHD), an insect repellant, was found to have acute peroral LD50 values in the rat of 9.85 ml/kg (males) and 4.92 ml/kg (females). Acute percutaneous LD50 values in the rabbit were 10.8 ml/kg (males) and 9.51 ml/kg (females). There were neither deaths nor signs of toxicity during or following a 6 hr exposure to a statically or dynamically generated substantially saturated vapor atmosphere. A 4 hr exposure to a high concentration (3.8 mg/liter) of a respirable aerosol of EHD (mass median aerodynamic diameter of 2.0 um) produced only minor signs of irritation during exposure, but no signs of toxicity. Occluded dermal contact with EHD on rabbits (4 and 24 hr) produced mild local erythema and, in several animals, edema. Contamination of the eye with EHD (0.005 to 0.1 ml) produced marked to severe conjunctivitis, with moderate iritis and diffuse corneal injury; healing occurred in most animals within 3 to 7 days. The major acute hazards with EHD are by swallowing and, to a greater extent, by contamination of the eye.

The acute toxicity and primary irritancy of N-benzyl-N,N-dimethylamine.

N-Benzyl-N,N-dimethylamine (BDMA), a polyester foam catalyst, was determined to have LD50 values of 0.65 (0.48-0.88) ml/kg perorally in the rat, and 1.66 (1.35-2.04) ml/kg by 24-hr occluded dermal contact in rabbits. The Lt50 for saturated vapor atmosphere exposure of rats was 35.4 min, and the 4-hr LC50 was 373 (311-447) ppm for rats and mice. Histological examination of the respiratory tract of animals exposed to BDMA concentrations of 277 ppm or higher revealed acute inflammatory changes in the nasal mucosa and pulmonary congestion. Unoccluded skin contact with 0.01 ml undiluted BDMA in rabbits produced moderate local erythema and edema. A 4-hr occluded contact resulted in local necrosis. Severe eye irritancy was produced by 0.005 ml undiluted BDMA and 0.5 ml 5% BDMA in propylene glycol; 1% BDMA was nonirritant to the eye. BDMA should be regarded as an acutely hazardous material by all routes of exposure.

Tellurium and tellurium dioxide: single endotracheal injection to rats.

Single endotracheal injections of tellurium and tellurium dioxide, at dosage levels sufficient to cause observable stress in rats, did not result in a progressive fibrotic tissue response after 180 days. The observation period of 180 days is insufficient to assess the lack of tumorigenic potential of these compounds and, therefore, no conclusions on this point are to be inferred.