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Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data from handbook or collection of data
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
review article or handbook
Title:
Sensory Irritation by Airborne Chemicals: A Basis to establish Acceptable Levels of Exposure
Author:
Yves, A. et al.
Year:
1986
Bibliographic source:
Toxicology of the nasal passages, Ed.: Craig S.Barrow, Chemical Industry Institute of Toxicology, Chapter 6, pp:91-100

Materials and methods

Type of study / information:
This publication describes the toxicological investigation of airborne chemicals in mice when exposed via inhalation with whole body plethysmography.
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Stimulation of trigeminal nerve endings located in the respiratory epithelium of the nasal mucosa by irritating airborne substances causes a variety of reflex reactions. These include inhibition of breathing, bradycardia, and a rise in systemic blood pressure. These reactions to airborne materials are indicative of a chemical's likelihood to irritate and potentially damage the respiratory tract. In particular, the inhibi¬tion of breathing is easy to measure in experimental animals. Using mice, an animal model has been developed based on their characteristic decrease in respiratory rate.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethylbenzene
EC Number:
202-849-4
EC Name:
Ethylbenzene
Cas Number:
100-41-4
Molecular formula:
C8H10
IUPAC Name:
ethylbenzene
Details on test material:
- Name of test material (as cited in study report): Ethylbenzene

Results and discussion

Any other information on results incl. tables

Stimulation of trigeminal nerve endings located in the respiratory epithelium of the nasal mucosa by irritating airborne substances causes a variety of reflex reactions. These include inhibition of breathing, bradycardia, and a rise in systemic blood pressure. These reactions to airborne materials are indicative of a chemical's likelihood to irritate and potentially damage the respiratory tract. In particular, the inhibi­tion of breathing is easy to measure in experimental animals. Using mice, an animal model has been developed based on their characteristic decrease in respiratory rate. Concentration-response relationships can be obtained from the RD50—the concentration necessary to decrease respiratory rate by 50%. It has been found that a good correlation exists between 0.03 RDso and the threshold limit values (TLVs) for 40 industrial chemicals. This finding provides an animal model that can be used to set exposure guidelines for the prevention of sensory irritation in humans.These studies have also revealed that a wide variety of chemicals act as sensory irritants. The mechanisms of their effect are reviewed and generally fit three categories: (1) reactivity toward nucleophilic groups, ,(2) cleavage of disulphide bonds, and (3) a purely physical mechanism involving the thermodynamic and solubility properties of the irritant in a lipid bilayer containing receptor proteins.

Applicant's summary and conclusion

Conclusions:
Stimulation of trigeminal nerve endings located in the respiratory epithelium of the nasal mucosa by irritating airborne substances causes a variety of reflex reactions. These include inhibition of breathing, bradycardia, and a rise in systemic blood pressure. These reactions to airborne materials are indicative of a chemical's likelihood to irritate and potentially damage the respiratory tract. In particular, the inhibi¬tion of breathing is easy to measure in experimental animals. Using mice, an animal model has been developed based on their characteristic decrease in respiratory rate. Concentration-response relationships can be obtained from the RD50—the concentration necessary to decrease respiratory rate by 50%. It has been found that a good correlation exists between 0.03 RDso and the threshold limit values (TLVs) for 40 industrial chemicals. This finding provides an animal model that can be used to set exposure guidelines for the prevention of sensory irritation in humans.These studies have also revealed that a wide variety of chemicals act as sensory irritants. The mechanisms of their effect are reviewed and generally fit three categories: (1) reactivity toward nucleophilic groups, ,(2) cleavage of disulphide bonds, and (3) a purely physical mechanism involving the thermodynamic and solubility properties of the irritant in a lipid bilayer containing receptor proteins.
Executive summary:

This publication describes the toxicological investigation of airborne chemicals in mice when exposed via inhalation with whole body plethysmography. The method for measuring respiratory rate in mice during exposure to airborne chemicals has been described as follows. Briefly, the tidal volume and respiratory rate of each animal are obtained by body plethysmography and recorded on an osciliograph, so that the characteristic pause during expiration can be observed as an indication of the presence of sensory irritation. The average respiratory rate of four mice simultaneously exposed is obtained from this recording. To obtain concentration-response relationships, 5-8 groups of 4 animals are used, each exposed to a different concentration of the chemical being investigated. From the concentration-response relationship, the RD50, i.e., the concentration necessary to decrease the respiratory rate by 50%, is calculated.

Stimulation of trigeminal nerve endings located in the respiratory epithelium of the nasal mucosa by irritating airborne substances causes a variety of reflex reactions. These include inhibition of breathing, bradycardia, and a rise in systemic blood pressure. These reactions to airborne materials are indicative of a chemical's likelihood to irritate and potentially damage the respiratory tract. In particular, the inhibi¬tion of breathing is easy to measure in experimental animals. Using mice, an animal model has been developed based on their characteristic decrease in respiratory rate. Concentration-response relationships can be obtained from the RD50—the concentration necessary to decrease respiratory rate by 50%. It has been found that a good correlation exists between 0.03 RDso and the threshold limit values (TLVs) for 40 industrial chemicals. This finding provides an animal model that can be used to set exposure guidelines for the prevention of sensory irritation in humans.These studies have also revealed that a wide variety of chemicals act as sensory irritants. The mechanisms of their effect are reviewed and generally fit three categories: (1) reactivity toward nucleophilic groups, ,(2) cleavage of disulphide bonds, and (3) a purely physical mechanism involving the thermodynamic and solubility properties of the irritant in a lipid bilayer containing receptor proteins.