To clarify the existence of a receptor protein for sensory irritants in trigeminal nerve endings, D- [i.e. (+)] and L- [i.e. (-)] enantiomers of alpha- and beta-pinene as models of nonreactive chemicals were evaluated for their potency in outbred OF1 and NIH/S mice using ASTM E981-84 bioassay. All pinenes possess sensory irritation properties and also induced sedation and signs of anaesthesia but had no pulmonary irritation effects. According to the ratio of RD50 (i.e. concentration which causes a 50% decrease in respiratory rate,f) and vapour pressure (Po), all pinenes are nonreactive chemicals. For nonreactive chemicals, Po and olive oil-gas partition (Loil) can be used to estimate their potency as sensory irritant. Thus, for enantiomers with identical physicochemical properties, the estimated RD50 values are the same. In addition, although alpha- and beta-pinene do not have identical Po and Loil values, their estimated potencies are quite close. However, the experimental results showed that D-enantiomers of pinenes were the most potent as sensory irritants and a difference in potency also exists between alpha- and beta-pinene. RD50 for D-enantiomers of alpha- and beta-pinene were almost equal, 1053 ppm and 1279 ppm in OF1 strain and 1107 ppm and 1419 ppm in NIH/S strain, respectively. Values differed by a factor of approximately 4 to 5 from L-beta-pinene for which the RD50 was 4663 ppm in OF1 and 5811 ppm in NIH/S mice. RD50 could not be determined for L-alpha-pinene; this pinene was almost inactive. D-alpha-pinene seems to best fit the receptor because its experimental RD50 was one-half of the estimated value while for D-beta-pinene those values were equal. On the contrary, L-beta-pinene was about 3 to 4 times less potent than estimated. L-alpha-pinene was only slightly active although it was estimated to be as potent as D-alpha-pinene. The remarkable difference in potency between L-enantiometers is most likely due to a structural difference between alpha- and beta-pinene: the more flexible beta-pinene can bend to fit into the receptor better than the rigid alpha-pinene. The results showed that the commonly used physicochemical descriptors cannot fully explain the potency of these chemicals; their three-dimensional structure should also be considered. Because of the stereospecificity of pinenes, a target site for nonreactive sensory irritants is most likely a receptor protein containing a chiral lipophilic pocket.

Animals↗

PubMedDate not supplied

Assessment of the cough reflex caused by inhalation of sodium lauryl sulfate and citric acid aerosols.

Guinea pigs were exposed for thirty minutes to a particulate aerosol of sodium lauryl sulfate at concentrations of 17.3, 28.9 and 48.6 mg/m3. The exposure chamber in which individual guinea pigs were exposed was fitted with a microphone to record coughing. As the concentration of sodium lauryl sulfate increased, the combined number and severity of the coughs increased and a fade in the response was also observed with exposure duration. Citric acid, a tussigenic agent commonly used to test antitussive agents was also tested using the same experimental protocol and was found to be about an order of magnitude less potent than sodium lauryl sulfate. This model could be useful in assessing the irritating properties of various aerosols to the tracheo-bronchial tree.

Aerosols↗

PubMedDate not supplied

Toxicity of smoke during chair smoldering tests and small scale tests using the same materials.

Toxicological evaluation of smoke produced during smoldering chair tests was undertaken by exposing mice to smoke emitted prior to, as well as following, flaming ignition of the chairs. By exposing several groups of mice, using undiluted smoke from the room containing the chairs, as well as various dilutions of the smoke, different levels of acute lethality were obtained. From these experiments, chairs constructed with polyurethane foam were found to create higher toxic atmospheres than chairs constructed with polyester or cotton fiber cushions. The same materials (polyurethane foam, polyester and cotton fibers) were also thermally decomposed in a small scale system and mice were exposed to the smoke to evaluate acute toxicity. Again polyurethane foam was found to produce smoke more toxic than smoke produced by polyester and cotton fibers. Sensory irritation monitored in mice during the smoldering tests indicated that an intense level of irritation was present long before large amounts of smoke were generated and long before flaming ignition occurred. The phenomenon of eye, nose and throat irritation would therefore be the first effect impeding escape attempts of individuals in a fire situation. Sensory irritation was followed by asphyxiation as evolution of carbon monoxide or hydrogen cyanide, or both, occurred. The same pattern of responses was observed with smoke generated with the small scale decomposition system.

Animals↗

PubMedDate not supplied

Comparison of the sensory irritation response in mice to chlorine and hydrogen chloride.

Groups of male Swiss-Webster mice were exposed to concentrations of chlorine varying from 0.7 to 38.4 ppm and to concentrations of hydrogen chloride varying from 40 to 943 ppm. The total exposure time to both gases was 10 minutes. Dose-response curves were plotted for both chlorine and hydrogen chloride, using the percentage decrease in respiratory rate during each exposure as the response reflecting sensory irritation of the upper respiratory tract. The results showed chlorine to be 33.0 times more irritating than hydrogen chloride, with 95% confidence limits of 18.6 and 57.1. Guidelines for obtaining a range of acceptable threshold limit values (TLV) based on sensory irritation of the upper respiratory tract are discussed. It was concluded that the current TLV of 1 ppm for chlorine is the upper acceptable limit, and that the established TLV of 5 ppm for hydrogen chloride lies at the lower limit of the predicted range. The mechanism of chlorine's and hydrogen chloride's sensory irritation may be explained by their reaction with various functional groups in the membranes of the trigeminal nerve endings lining the nasal mucosa.

Animals↗

PubMedDate not supplied

Sensory irritation and incapacitation evoked by thermal decomposition products of polymers and comparisons with known sensory irritants.

A decrease in respiratory rate in mice during exposure to irritating airborne chemicals has been utilized as a response parameter to characterize the degree of upper respiratory tract irritation (sensory irritation) to the thermal decomposition products of various polymers. These included polystyrene, polyvinyl chloride, flexible polyurethane foam, polytetrafluorethylene, a fiber glass reinforced polyester resin, and Douglas Fir. Each of the materials was thermally decomposed in a low-mass vertical furnace in an air atmosphere at a programmed heating rate of 20 degrees C/min. Mice, in groups of four, were exposed to graded concentrations of the thermal decomposition products of each of the above materials. Dose-response curves were obtained by utilizing the maximum percent decrease in respiratory rate as the response parameter during each exposure. Comparison of these dose-response curves with other sensory irritants such as chlorine, ammonia, hydrogen chloride, sulfur dioxide, and toluene diisocyanate gave an indication of the sensory irrtation potential of the thermal decomposition products of these various polymers versus that of well-known single airborne chemical irritants. Total stress and incapacitation of the organism during exposure to sensory irritants such as from the thermal decomposition products of synthetic polymers is discussed.

Air Pollutants↗

PubMedDate not supplied

Sensory irritation of select experimental photochemical oxidants.

Groups of male Swiss-Webster mice were exposed to photochemical oxidant mixtures generated by reacting various hydrocarbons with nitrogen dioxide in the presence of ultraviolet light while their respiratory rates were monitored. The hydrocarbons used were 1,3-butadiene, 1-butene, cis-2-butene, ethylene, propylene, n-butane, and ethane. The initial hydrocarbon concentrations ranged from .4 to 18 ppm, with the initial nitrogen dioxide concentration being one-third that of the initial hydrocarbon concentration. New groups (four mice per group) were exposed for 5 min at 0, 1, 2, 3, and 4 hr of ultraviolet irradiation. Dose-response curves for each hydrocarbon were developed by plotting the maximum percent decrease in respiratory rate observed during the 4 hr of irradiation of each mixture as a function of the initial hydrocarbon concentration present. The percent decrease in respiratory rate in mice was chosen as an index of the sensory irritation of the upper respiratory tract for each mixture. The results showed that the potency of the photochemical oxidant mixtures generated from the hydrocarbons to be propylene greater than 1,3,-butadiene = 1-butene=cis-2-butene greater than ethylene. When ethane or n-butane was used, no decrease in respiratory rate was observed. These results are compatible with the data obtained in human volunteer studies. Guidelines for relating the percent decrease in respiratory rate in mice to human reactions are presented.

Animals↗

PubMedDate not supplied

Sensory irritating potency of some microbial volatile organic compounds (MVOCs) and a mixture of five MVOCs.

The authors investigated the ability/potencies of 3 microbial volatile organic compounds and a mixture of 5 microbial volatile organic compounds to cause eye and upper respiratory tract irritation (i.e., sensory irritation), with an animal bioassay. The authors estimated potencies by determining the concentration capable of decreasing the respiratory frequency of mice by 50% (i.e., the RD50 value). The RD50 values for 1-octen-3-ol, 3-octanol, and 3-octanone were 182 mg/m3 (35 ppm), 1359 mg/m3 (256 ppm), and 17586 mg/m3 (3360 ppm), respectively. Recommended indoor air levels calculated from the individual RD50 values for 1-octen-3-ol, 3-octanol, and 3-octanone were 100, 1000, and 13000 microg/m3, respectively-values considerably higher than the reported measured indoor air levels for these compounds. The RD50 value for a mixture of 5 microbial volatile organic compounds was also determined and found to be 3.6 times lower than estimated from the fractional concentrations and the respective RD50s of the individual components. The data support the conclusion that a variety of microbial volatile organic compounds may have some synergistic effects for the sensory irritation response, which constrains the interpretation and application of recommended indoor air levels of individual microbial volatile organic compounds. The results also showed that if a particular component of a mixture was much more potent than the other components, it may dominate the sensory irritation effect. With respect to irritation symptoms reported in moldy houses, the results of this study indicate that the contribution of microbial volatile organic compounds to these symptoms seems less than previously supposed.

Air Microbiology↗