2,2'-(ethylenedioxy)diethanol

Specific investigations: other studies

Link to relevant study record(s)

Reference

Endpoint:

specific investigations: other studies

Remarks:

inhalation: sensory irritation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

The objective of this study was to evaluate sensory irritation in mice during a single 30-minute exposure to the test substance aerosol and to further assess the respiratory response.

GLP compliance:

yes (incl. QA statement)

Type of method:

in vivo

Endpoint addressed:

respiratory irritation

Species:

mouse

Strain:

Swiss Webster

Sex:

male

Details on test animals or test system and environmental conditions:

- All animals were designated by the supplier to be approximately 32 days old and 20-22 g upon arrival.
- Animals were housed in a relocatable containment system unit from arrival to termination of the study except during exposures. All animals were assigned unique numbers and identified by cage tage. Animals considered available or animals placed on study were also identified by a tail marking procedure.
- The animals were housed 2/cage in stainless steel, wire mesh cages 23.5 x 20 x 18 cm. DACBO was placed under each cage and changed regularly. Cages were changed and sanitized at least once every 2 weeks. An automatic timer was set to provide fluorescent lighting for a 12-hour photoperiod (approximately 05.00 to 17.00 hours for the light phase). Temperature and relative humidity were recorded. Temperature was routinely maintained at 66-77°F; relative humidity was routinely maintained at 40-70%.
- Tap water was available ad libitum except during exposures and was delivered by an automatic watering system with demand control values mounted on each rack and water bottles. Water analyses were provided by the supplier at regular intervals. EPA standards for maximum levels of contaminants were not exceeded. Pelleted, certified animal Diet Rat, Hause, Hamster 3000 was available ad libitum except during exposures. Analyses for chemical composition and possible contaminants of each feed lat were performed by Agway Inc., and the results were included in the raw data.
- The animals were acclimated to laboratory conditions for at least 7 days prior to exposure to the test substance.

Route of administration:

inhalation: aerosol

Vehicle:

not specified

Details on exposure:

- Type of inhalation exposure: head only
- The mass median aerodynamic diameters representative of the exposures were determined to be 2.60, 2.45, 2.70, and 3.10 µm for the 3.601, 4.545, 4.744, and 5.099 mg/L exposure concentrations, with geometric standard deviations which ranged from 2.30 to 3.06.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

30 min

Frequency of treatment:

Single dose

Post exposure period:

7 days

Dose / conc.:

3.601 mg/L air

Dose / conc.:

4.545 mg/L air

Dose / conc.:

4.744 mg/L air

Dose / conc.:

5.099 mg/L air

No. of animals per sex per dose:

4 males

Control animals:

yes

Examinations:

Monitors for toxic effects included clinical observations and body weights.

Positive control:

no

Details on results:

No mortality was observed during the exposures or following exposure. The only clinical signs observed during the study were periocular wetness and ocular opacities observed in animals exposed to 4.744 and 5.099 mg/L of the test substance as aerosol. Mean body weight gain was observed for the 3.601 mg/L group an postexposure day 7. A slight loss In mean body weight was observed for the 4.454, 4.744, and 5.099 mg/L groups. Due to the lack of a concentration-related response and the minimal changes observed, these effects on body weight were not believed to be exposure related. The mean respiratory rate decreases in mice exposed to the test substance as aerosol were 15.2, 27.3, 58.1, and 43.7% for the 3.601, 4.545, 4.744, and 5.099 mg/L exposure concentrations, respectively.

The sensory irritation potential of the test substance in male Swiss Webster mice was investigated. Groups of 4 mice were exposed head-only to the test substance as aerosol for 30 minutes. Sensory irritation was assessed by monitoring the respiratory rate of each animal prior to the exposure, during the exposure, and during a 10-minute recovery period. The animals were observed for 7 days following the exposure. Monitors for toxic effects included clinical observations and body weights. Exposure concentrations of 3.601, 4.545, 4.744, or 5.099 mg/L were measured. The mass median aerodynamic diameters representative of the exposures were determined to be 2.60, 2.45, 2.70, and 3.10 µm for the 3.601, 4.545, 4.744, and 5.099 mg/L exposure concentrations, with geometric standard deviations which ranged from 2.30 to 3.06.

No mortality was observed during the exposures or following exposure. The only clinical signs observed during the study were periocular wetness and ocular opacities observed in animals exposed to 4.744 and 5.099 mg/L test substance as aerosol. The mean respiratory rate decreases in mice exposed to the test substance as aerosol were 15.2, 27.3, 58.1, and 43.7% for the 3.601, 4.545, 4.744, and 5.099 exposure concentrations, respectively. During exposure, the waveform of the respiratory cycle changed from that usually seen in air-exposed animals to include a notching or lengthening of the expiratory portion of the waveform which results in a decreased respiratory rate. Such a characteristic waveform is considered to be an indicator of the sensory irritation response. At high exposure concentrations of the test substance as aerosol, the notching was more pronounced and resulted in a decreased respiratory rate. During the recovery period, mean respiratory rates began to return to control values for each exposure group.

A concentration-response curve was plotted with the common logarithm of the exposure concentration as the independent variable and the percent decrease in respiratory rate as the dependent variable. The RD50 or concentration of the test substance which produced a 50 percent decrease in respiratory rate, was determined to be 5.14 mg/L, with a 95 confidence interval of 3.77-7.10 mg/L.

Description of key information

The RD50 or concentration of the test substance which produced a 50 percent decrease in respiratory rate, was determined to be 5.14 mg/L, with a 95 confidence interval of 3.77-7.10 mg/L.

Additional information

In a non-GLP study, the sensory irritation potential of the test substance in male Swiss Webster mice was investigated. Groups of 4 mice were exposed head-only to the test substance as aerosol for 30 minutes. Sensory irritation was assessed by monitorlng the respiratory rate of each animal prior to the exposure, during the exposure, and during a 10-minute recovery period. The animals were observed for 7 days following the exposure. Monitors for toxic effects included clinical observations and body weights. Exposure concentrations of 3.601, 4.545, 4.744, or 5.099 mg/L were measured. No mortality was observed during treatment. Clinical signs were periocular wetness and ocular opacities observed in animals exposed to 4.744 and 5.099 mg/L. The mean respiratory rate decreases in mice exposed to the test substance as aerosol were 15.2, 27.3, 58.1, and 43.7% for the 3.601, 4.545, 4.744, and 5.099 exposure concentrations, respectively. During exposure, the waveform of the respiratory cycle changed from that usually seen in air-exposed animals to include a notching or lengthening of the expiratory portion of the waveform which results in a decreased respiratory rate. Such a characteristic waveform is considered to be an indicator of the sensory irritation response. At high exposure concentrations of the test substance, the notching was more pronounced and resulted in a decreased respiratory rate. During the recovery period, mean respiratory rates began to return to control values for each exposure group. The RD50 or concentration of the test substance which produced a 50 percent decrease in respiratory rate, was determined to be 5.14 mg/L, with a 95 confidence interval of 3.77-7.10 mg/L.

Results of the study indicate respiratory irritation potential of the test substance. However, no classification on respiratory irritation can be made in accordance with Regulation (EC) No. 1272/2008, as the study only investigates the repiratory rate (RD50). No useful information on clinical signs of toxicity (dyspnoea, rhinitis etc) and histopathology (e.g. hyperemia, edema, minimal inflammation, thickened mucous layer) is taken into account.