Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well described study published in a peer reviewed scientific journal.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
30 minutes inhalation head only exposure of aerosols
GLP compliance:
not specified
Test type:
other: 30 min inhalation exposure

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
aerosol dispenser: not specified
Remarks:
migrated information: aerosol
Details on test material:
- Name of test material (as cited in study report): hexadecyl trimethyl ammonium bromide (HTA)
Aerosols from cetrimonium bromide dissolved in saline water.
Obtained by Fluka Chemie GmbH (Buchs, Switzerland)
In the publication, the CAS no. of cetrimonium chloride (112-02-7) is given by mistake instead of the CAS no for cetrimonium bromide. This has later been verified by the authors.

Test animals

Species:
mouse
Strain:
Balb/c
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Taconic, Silkeborg Denmark
- Weight at study initiation: Mean weight 19.4g; SD 1.7g
- Housing: Polypropylene cages with pinewood sawdust bedding
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2 °C
- Humidity (%): 50±5%
- Photoperiod (hrs dark / hrs light): From 6 am to 6 pm

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
head only
Vehicle:
other: saline water
Details on inhalation exposure:
Mice were placed in separate body plethysmographs and exposed to a saline aerosol for 15 min followed by an exposure period of 30 min. Hereafter exposed to clean air for 45 min for recovery.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric measurement of aerosols
Duration of exposure:
30 min
Concentrations:
control: 0 mg/m3
exposure level 1: 0.33% cetrimonium bromide solution generating exposure level of 0.57 mg cetrimonium bromide /m3
exposure level 2: 1% cetrimonium bromide solution generating exposure level of 1.8 mg cetrimonium bromide /m3
exposure level 3: 3.3% cetrimonium bromide solution generating exposure level of 5.3 mg cetrimonium bromide /m3
exposure level 4: 10% cetrimonium bromide solution generating exposure level of 19 mg cetrimonium bromide /m3
No. of animals per sex per dose:
7-8 animals per dose level
Control animals:
yes
Details on study design:
Observation of respiratory parameters was done during exposure (respiratory rate; tidal volume).
Airway inflammation was examined 16 hours after end of exposure by examination of BAL (Bronchoalveolar lavage fluid).

Observation of respiratory parameters

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
other: LOEC
Effect level:
1.8 mg/m³ air
Based on:
test mat.
Exp. duration:
30 min
Remarks on result:
other: Based on reduced tidal volume
Sex:
female
Dose descriptor:
other: NOEC
Effect level:
0.57 mg/m³ air
Based on:
test mat.
Exp. duration:
30 min
Remarks on result:
other: Based on tidal volume
Other findings:
Dose dependent decrease in tidal volume. Fully reversible for lower concentrations and only slightly reversible at the highest exposure level during the 45-min recovery period. The tidal volume reduction was time-dependent and concentration-dependent.
Also dose dependent increase in respiratory frequency.
As for other quaternary ammonium compounds tested in the study an increase in macrophages was observed in BAL (only at highest dose-level aand less pronounced as for benzalkoniium chloride)

Applicant's summary and conclusion

Interpretation of results:
other: STOT SE 3 - H335
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Inhalation of cetrimonium bromide induced deep lung effects with decrease in tidal volume and increase in repsiratory frequency corresponidng effects known to occurrr from deep lung effects/ irritation (contrary to sensory irritation in the upper respiratory tract)) . As for other quaternary ammonium compounds tested in the study an increase in macrophages was observed in BAL (only at highest dose-level and less pronounced as for benzalkonium chloride) . The NOEL value based on reduction in tidal volume at 0.57 mg/m3 for inhalation of aerosols of cetrimonium bromide.
Executive summary:

The reported study examined the pulmonary effects ( irritation and inflammation) in connection with 30 minutes of inhalation of aerosols of quaternary ammonium compounds in mice. Inhalation of cetrimonium bromide induced dose related effects on tidal volume and respiratory frequency at a LOEC of 1.8 mg cetrimonium bromide /m3 as a response from deep lung effects and also induced initial signs in relation to lung inflammation (increased level of macrophages in BAL) at the highest test concentration (19 mg/m3). The NOEC value based on reduction in tidal volume was 0.57 mg/m3 for inhalation of aerosols of cetrimonium bromide.

These data indicate that classification as a respiratory irritant (STOT SE 3, H335) would be appropriate.