Registration Dossier

Administrative data

Endpoint:
specific investigations: other studies
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Data from secondary literature with collections of data from experimental studies, no details on experimental procedures and test results; reliability of data is not assignable

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Recherche de la relations entre toxicite de molecules d'interet industriel et proprietes physico-chimiques: test d'irritation des voies aeriennes superieures applique a quatre familles chimiques (In French)
Author:
Muller J, Greff G
Year:
1984
Bibliographic source:
Fd Chem Toxicol 22: 661-664
Reference Type:
review article or handbook
Title:
Evaluation of the sensory irritation test for the assessment of occupational health risk
Author:
Bos PMJ, Zwart A, Reuzel PGJ, Bragt PC
Year:
1992
Bibliographic source:
Crit Rev Toxicol 21: 423-450
Reference Type:
publication
Title:
Physicochemical properties of nonreactive volatile organic chemicals to estimate RD50: alternatives to animal studies
Author:
Alarie Y, Nielsen GD, Andonian-Haftvan J, Abraham MH
Year:
1995
Bibliographic source:
Toxicol Appl Pharmacol 134: 92-99
Reference Type:
review article or handbook
Title:
Development of a database for sensory irritants and its use in establishing occupational limits
Author:
Schaper M
Year:
1993
Bibliographic source:
Am Ind Hyg Assoc J 54: 488-544

Materials and methods

Principles of method if other than guideline:
Alarie test
Type of method:
in vivo
Endpoint addressed:
respiratory irritation

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
other: Swiss OF1

Administration / exposure

Route of administration:
inhalation: vapour
Duration of treatment / exposure:
5 to 15 min
Frequency of treatment:
single
Doses / concentrations
Remarks:
Doses / Concentrations:

Basis:

Examinations

Examinations:
RD 50: concentration that induces a 50 % decrease in the respiratory rate

Results and discussion

Details on results:
RD 50 = 100 ppm = 0.5 mg/L

Applicant's summary and conclusion

Conclusions:
With a RD50 of 100 ppm a comparably low concentration of acetophenone was needed to induce sensory irritation in mice.
Executive summary:

A sensory irritation test (Alarie test) based on trigeminal nerve stimulation in the nasal mucosa of mice measures decreased respiratory frequency which is described as RD50 -value (= 50% decrease in the respiratory rate). For acetophenone a RD50 -value of 0.5 mg/l (= 100 ppm) was reported for Swiss OF1 mice in several review-like publications with compilations of RD-50 values for many substances. A comparably low concentration of acetophenone was needed to induce sensory irritation in this assay. However, details on experimental conditions and test results are unsufficiently documented in these publications, so that a reliability is not assignable.

 

Other authors have published that there was no dose-relationship nor histopathological changes (D. Zissu. Journal of Applied Toxicology, 1995, Vol: 15(3):207-213): “These experiments showed that the lesion intensity observed in the nasal passages varied with exposure duration and type of airborne chemical, but did not depend on the concentration of the substance. Results did not allow us to establish a relationship between the histopathological changes and the type of chemical family”. Further supported by Bos et al. (J Occup Environ Med., 2002, Oct;44(10):968-76): “No relation was found between the sensory irritation potential (as measured by the Alarie test) and local tissue damage (histopathological changes) in the respiratory tract after single or repeated exposure. It was concluded that the Alarie test is inappropriate to evaluate respiratory tract irritation. In addition, the available data do not support a quantitative potency ranking for man based on the RD50 obtained with experimental animals.”

Pinching study (Pinching and Doving, 1974, Brain Res., 82: 195-204) indicated the same conclusion in its summary: no dose effect relationship and was also of reliability 4, even if ACP was used at 1 dose and we did not found the primary source of the study.