Ethoxyquin

Acute Toxicity: inhalation

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 guideline

Test guideline 1

Qualifier:

according to guideline

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.

Test guideline 2

Qualifier:

equivalent or similar to guideline

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

Test material information

Constituent 1

Reference substance name:

Ethoxyquin

EC Number:

202-075-7

EC Name:

Ethoxyquin

Cas Number:

91-53-2

Molecular formula:

C14H19NO

IUPAC Name:

ethoxyquin

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 or test system 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:

other: 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 on

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.