Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
Peer-reviewed assessment report (attached in section 13)

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Version / remarks:
US EPA FIFRA Guideline § 81-3
Deviations:
yes
Remarks:
Purity of the test compound was not determined by the laboratory prior to conduct of the test.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not applicable
GLP compliance:
yes
Remarks:
self-certified to US EPA regulations at 40 CFR Parts 160 and 792
Test type:
other: application of highest technically achieveable dose
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Chemical name
IUPAC: 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline
CAS: 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline

Test animals

Species:
rat
Strain:
other: Crl:CD®BR rats
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, MI

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
not specified
Mass median aerodynamic diameter (MMAD):
3.2 µm
Geometric standard deviation (GSD):
2.4
Remark on MMAD/GSD:
100 % of the particles < 10 microns and 13.4 % < 1.18 microns
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass and stainless steel whole-body exposure inhalation chamber (NYU type)
- Exposure chamber volume: 0.5 m3 (500 L)
- Source and rate of air: The exposure chamber was operated at 134 to 143 litres per minute (LPM). An airflow of 100 LPM is sufficient to sustain 12 air changes per hour in a 0.5 m3 chamber; therefore, the protocol specified 12 to 15 air changes per hour was met and/or exceeded.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The test material was administered as a liquid droplet aerosol (3.2 micron MMAD with a geometric standard deviation of 2.4; 100 % of the particles < 10microns and 13.4 % < 1.18 microns) at an airborne concentration of 1.97 mg/L. The nominal concentration for the test atmosphere should have been 9.2 mg/L but was not reached for technical reasons.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
1.97 mg/L
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were monitored on Day 0 (initiation) and for the following 14 days before scheduled sacrifice.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.97 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
One animal was euthanised in extremis on Day 1 following exposure whereas all the other rats survived throughout the dosing and observation periods.
Clinical signs:
Clinical signs during and immediately after the exposure included salivation (during the exposure); wet and/or dried yellow material on various external surfaces, salivation, dried red material around nose, and dried yellow material around right eye at one hour after exposure.
Significant clinical findings noted during Day 1 to Day 14 included tremors; unkempt appearance; dried red material around eyes, nose, and mouth; dried yellow material around eyes; decreased defecation; wet and/or dried brown material on various body surfaces; and wet and/or dried yellow material on various body surfaces.
The rat that was euthanised on day 1 exhibited reduced activity, complete eye closure, impaired muscle coordination, body cool to touch, decreased respiration rate, shallow respiration, clear discharge in both eyes, and wet yellow material over the entire body surface.
Body weight:
A male and a female rat lost 27 and 3 grams, respectively, from Day 0 to Day 3. An additional female rat gained no weight from Day 0 to Day 3. All animals that survived recovered to or surpassed their initial (Day 0) body weights by Day 14.
Other findings:
There were no other significant clinical findings or body weight changes during the study.

Any other information on results incl. tables

Conclusion:

Ethoxyquin was of rather low acute inhalative toxicity to rats although the death of one female animal on Day 1 was considered to be treatment-related because of the toxic signs of impaired muscle coordination, hypothermic body temperature, and depressed and shallow respiration. The necropsy observation of dark red intestinal contents indicated possible effects on the gastrointestinal tract.

The remaining five males and four females survived through the 14-day observation period with only very minor and transitory effects on body weight and no exposure-related gross pathologic abnormalities. The occurrence of tremours in 6 of 10 animals following inhalation exposure, however, might suggest a neurotoxic potential and is considered to be in line with the frequent observation of ataxia in the acute oral toxicity study.

Because of the study design (whole-body exposure), the toxic signs might be also (at least partly) due to oral intake of traces of the test substance from the fur and it cannot be certainly stated that they were exclusively caused by inhalation.

On the basis of this study, the acute inhalation LC50 of ethoxyquin for both sexes was found to be in excess of 1.97 mg/L. In accordance with Annex VI of Commission Directive 2001/59/EC, ethoxyquin does not need to be classified with respect to acute inhalation toxicity.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Conclusions:
As information was provided via a peer-reviewed assessment report, it can be considered as sufficiently reliable to assess the acute inhalation toxicity of ethoxyquin towards rats. On the basis of this study, the acute inhalation LC50 of ethoxyquin for both sexes was found to be in excess of 1.97 mg/L. In accordance with Annex VI of Commission Directive 2001/59/EC, ethoxyquin does not need to be classified with respect to acute inhalation toxicity. Based on this data however, a LC50 of 5 mg/l cannot be excluded, and so not the necessity for a classification as acute toxic cat. 4 acc. Regulation 1272/2008.
Executive summary:

In an acute inhalation toxicity study (US EPA FIFRA Guideline § 81-3, equivalent to OECD 403), groups of Crl:CD®BR rats (5/sex) were exposed by inhalation route ethoxyquin for 4 hours to whole body at a concentration of 1.97 mg/L.  Animals then were observed for 14 days.

 

LC50combined > 1.97  mg/L

 

One animal was euthanise din extremis on Day 1 following exposure whereas all the other rats survived throughout the dosing and observation periods. Ethoxyquin is classified as being of low Toxicity, classification as acute toxic cat. 4 acc. Regulation 1272/2008 cannot be excluded.