Registration Dossier

Administrative data

Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 January - 21 May 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP /guideline study
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Type of study / information:
Standard RD50 (50% depression in respiration rate) study
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
According to the procedures outlined in ASTM E 981-04 (Standard Test Method for Estimating Sensory Irritancy of Airborne Chemicals).
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: vapour
Details on test material:
-Name of test material (as cited in study report): 1,3 and 1,4-Cyclohexanecarboxaldehyde
- Composition of test material, percentage of components: A mixture of 1,3-Cyclohexanedicarboxaldehyde and 1,4-Cyclohexanedicarboxaldehyde
- Lot/batch No.: Lot# 201200123-WFE 2-3Mr
-The purity of the test material was determined to be 98.24 ± 0.44%

Results and discussion

Any other information on results incl. tables

There were no in-life observations noted during the one-week post-exposure period. Mean body weights for all exposure groups returned to or exceeded pre-exposure (test day 1) values by test day 4. A concentration-dependent decrease in respiration rate was observed. The mean maximum decreases in respiratory rate for each of the exposure groups were as follows: 29% (8.9 ppm), 24% (11.0 ppm), 46% (15.2 ppm), 58% (18.5 ppm), 63% (18.8 ppm), 63% (21.5 ppm), 69% (23.5 ppm), and 73% (25.5 ppm). The average percent recovery during the ten-minute period immediately following the end of exposure for the 8.9, 11.0, 15.2, 18.5, 18.8, 21.5, 23.5, and 25.5 ppm experimental groups was 77%, indicating that the treatment-induced respiratory depression was largely reversible.

The RD50 of inhaled 1,3- and 1,4-Cyclohexanedicarboxaldehyde was determined to be 15.9 ppm, with a 95% confidence interval of 10.9 - 23.1 ppm.

Applicant's summary and conclusion

Conclusions:
The RD50 of inhaled 1,3- and 1,4-Cyclohexanedicarboxaldehyde was determined to be 15.9 ppm, with a 95% confidence interval of 10.9 - 23.1 ppm.
Executive summary:

This study was conducted to evaluate the sensory irritant potential of inhaled 1,3- and 1,4-Cyclohexanedicarboxaldehyde in adult Swiss Webster (CFW) mice. The concentration of test material (1,3- and 1,4-Cyclohexanedicarboxaldehyde), which resulted in a 50% depression in respiration rate (RD50), was determined according to procedures outlined in ASTM E 981-04 (Standard Test Method for Estimating Sensory Irritancy of Airborne Chemicals). Groups of four male Swiss Webster (CFW) mice were exposed for thirty minutes to 8.9, 11.0, 15.2, 18.5, 18.8, 21.5, 23.5, or 25.5 ppm 1,3- and 1,4- Cyclohexanedicarboxaldehyde (exposure concentrations based on measured data from gravimetric determinations). Mice were allowed a ten-minute acclimation period before the exposure/monitoring cycle began. After the ten-minute acclimation period, the exposure/monitoring cycle was initiated and baseline respiratory rate data (breaths/minute) for each mouse were collected for a ten-minute period. Test material exposure was then initiated and mice were exposed for 30 minutes with continuous collection of respiratory rate data for each mouse. Respiratory rate during a ten-minute recovery period was recorded after the end of exposure. The mice were held for seven days following exposure, during which time body weights and clinical observations were monitored to assess any untoward effects of exposure. All animals survived the 30-minute exposure to the test material as well as the one-week post-exposure period. There were no in-life observations noted during the one-week post-exposure period. Mean body weights for all exposure groups returned to or exceeded pre-exposure (test day 1) values by test day 4. A concentration-dependent decrease in respiration rate was observed. The mean maximum decreases in respiratory rate for each of the exposure groups were as follows: 29% (8.9 ppm), 24% (11.0 ppm), 46% (15.2 ppm), 58% (18.5 ppm), 63% (18.8 ppm), 63% (21.5 ppm), 69% (23.5 ppm), and 73% (25.5 ppm). The average percent recovery during the ten-minute period immediately following the end of exposure for the 8.9, 11.0, 15.2, 18.5, 18.8, 21.5, 23.5, and 25.5 ppm experimental groups was 77%, indicating that the treatment-induced respiratory depression was largely reversible.