2,2-dimethyl-1,3-dioxolan-4-ylmethanol

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 02 March to 29 May 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,2-dimethyl-1,3-dioxolan-4-ylmethanol

EC Number:

202-888-7

EC Name:

2,2-dimethyl-1,3-dioxolan-4-ylmethanol

Cas Number:

100-79-8

Molecular formula:

C6H12O3

IUPAC Name:

(2,2-dimethyl-1,3-dioxolan-4-yl)methanol

Test material form:

liquid

Specific details on test material used for the study:

- Analytical purity: 99.7%
- Composition of test material, percentage of components: 99.7% 2,2-Dimethyl-1,3-dioxolane-4-methanol; water: 0.07%; Acidity (Acetic acid): 0.008%
- Lot/batch No.: BR14I1865
- Expiration date of the lot/batch: 17 September 2015
- Storage condition of test material: at room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Model and Services, Germany GmbH (Sandhofer Weg 7, D-97633, Sulzfeld, Germany)
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Sighting exposure: approximately 12 weeks old / Main study: approximately 9 weeks old
- Weight at study initiation: Sighting exposure: 413 g (male) and 270 g (female) / Main study: 385-432 g (males) and 230-251 g (females).
- Fasting period before study: not mentioned
- Housing: Standard housing conditions (Group caging (5 animals, by sex, per cage) during the main study; individual caging during the sighting study)
- Diet (e.g. ad libitum): The animals were provided with ssniff SM R/M “Autoclavable Complete Feed for Rats and Mice – Breeding and Maintenance” (ssniff Spezialdiäten GmbH, D-59494 Soest,
Germany) ad libitum
- Water (e.g. ad libitum): tap water from the municipal supply, as for human consumption from 500 ml bottles ad libitum.
- Acclimation period: Animals were acclimated to laboratory conditions for 39 days (sighting study) or 15 days (main study) prior to involvement in the study. Animals were also acclimatised to the test apparatus (restrain procedures) for a short period prior to testing in order to lessen the stress during exposure.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 – 24.8 °C
- Humidity (%): 30 – 70 %
- Air changes (per hr): At least 15 air exchanges per hour
- Photoperiod (hrs dark / hrs light): 12 hours of continuous artificial light in each twenty four hour period (from 6.00 a.m. to 6.00 p.m.)

IN-LIFE DATES: From: 02 March 2018 To: 20 March 2018

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

3.81 µm

Geometric standard deviation (GSD):

2.01

Remark on MMAD/GSD:

Above-mentioned values concern the main study.

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The animals were exposed, nose-only, to an atmosphere of the test item using a TSE Rodent Exposure System (TSE Systems GmbH, Bad Homburg, Germany). This system comprises of two concentric anodised aluminium chambers and a computer control system incorporating pressure detectors and mass flow controllers.
- Exposure chamber volume: 3.85 L
- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber. Only the nose of each animal was exposed to the test atmosphere.
- Source and rate of air: Dried compressed air was supplied by means of an oil-free compressor and passed through a suitable filter system prior to introduction to the nebuliser. The flow of air through each port was at least 0.5 L/min (between 17.3 and 21.5 L/min).
- Method of conditioning air: Fresh aerosol from the generation system was constantly supplied to the inner plenum (distribution chamber) of the exposure system from where, under positive pressure, it was distributed to the individual exposure ports.
- System of generating particulates/aerosols: The test item was aerosolized using a stainless steel concentric jet nebulizer (TSE Systems GmbH, Bad Homburg, Germany) located at the top of the exposure chamber. The rate of test item usage was controlled by a syringe pump.
- Method of particle size determination: The particle size of the test atmosphere was determined three times during the exposure period using a 7-stage impactor of Mercer style (TSE Systems GmbH, Bad Homburg, Germany). Such devices employ an inertial separation technique to isolate particles in the discrete aerodynamic size ranges. Samples were taken from an unoccupied exposure port (representing the animal’s breathing zone). The collection substrates and the backup filter were weighed before and after sampling and the weight of test item, collected at each stage, calculated by this difference.
- Treatment of exhaust air: After passing through the animal’s breathing zone, used aerosol entered the outer cylinder from where it was exhausted through a suitable filter system.
- Temperature, humidity, pressure in air chamber: temperature between 20.4 and 22°C; humidity between 4 and 7%. Relative pressures within the system were constantly monitored and
controlled by the computer system.

TEST ATMOSPHERE
- Brief description of analytical method used: The nominal concentration was calculated by dividing the mass of test material disseminated into the chamber by the total volume of air that passed through the chamber during the same period.
- Samples taken from breathing zone: yes : The test atmosphere concentration was sampled in the breathing zone during the 4-hour exposure period 13-17 times at approximately equal intervals during the study.

VEHICLE
- Composition of vehicle (if applicable): none no control animmals)
- Concentration of test material in vehicle (if applicable): N/A
- Justification of choice of vehicle: N/A
- Lot/batch no. (if required): N/A
- Purity: N/A

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Sighing exposure: Inhalable fraction (<4 μm) = 53.8% / Main study: Inhalable fraction (<4 μm) = 52.8%
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The mass median aerodynamic diameters (MMAD) were 3.75 μm and 3.81 μm with geometric standard deviations (GSD) of 1.97 and 2.01 in the Sighting Group and the Main Group, respectively.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: In the absence of information on the effects of the substance by inhalation, a limit concentration of 5 mg/L was tested in a "sighing" study

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The nominal concentration was calculated by dividing the mass of test material disseminated into the chamber by the total volume of air that passed through the chamber during the same period.

Duration of exposure:

4 h

Concentrations:

5 mg/L in the sighing and main studies

No. of animals per sex per dose:

6 (1 animal/sex in the sighing study; 5 animals/sex in the main study)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for clinical signs at hourly intervals during exposure whilst the animals were still restrained. Following exposure, clinical observations were performed twice on the day of exposure (following removal from the restrainer and approximately one hour after completion of the exposure) and subsequently once daily for 14 days. Individual body weights were recorded prior to treatment on the day of exposure (before the exposure on Day 0) and on Days 1, 3, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: All rats, irrespective of the day of death, were subject to a gross necropsy which included a detailed examination of the abdominal and thoracic cavities. Special attention was given to the respiratory tract for macroscopic signs of irritancy or local toxicity.

Results and discussion

Preliminary study:

The mean achieved atmosphere concentration in the sighing study was 5.04 mg/L.No mortality was noted during the study.
Laboured respiration (slight to moderate) was recorded in both animals of the study on Day 0. Red-brown staining and/or wet fur were also observed in both animals on Day 0. These observations were considered to be related to the restraint and exposure procedures and were considered not to be toxicologically significant.
Each rat was symptom-free from Day 1.
Slight body weight loss was noted in both animals by Day 3, but thereafter, positive change was recorded in body weights. Both rats returned to their initial
body weights by approximately Day 7.
No external or internal findings were recorded at necropsy in any animals.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

discriminating conc.

Effect level:

5.11 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No animals died during the study.

Clinical signs:

other: Laboured respiration (slight to moderate) was recorded in all animals of the study on Day 0. Red-brown staining and/or wet fur were also observed in all study animals on Day 0. These observations were considered to be related to the restraint and exposure

Body weight:

Slight body weight loss (0.7-2.2 %) was observed in 4 male and 2 female animals on Day 1 but no further body weight loss was noticed thereafter. All affected animals of this group normalised in the body weight by Day 3.

Gross pathology:

No external or internal findings were recorded at necropsy in any animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, no mortality occurred in main study animals when exposed to a test atmosphere concentration of 5.11 mg/L for 4 hours. The acute inhalation median lethal concentration (LC50) of AUGEO SL 191 in Wistar Crl:WI rats was therefore considered to be above 5.11 mg/L. AUGEO SL 191 is non-toxic after acute inhalative administration and is therefore not classified according to Regulations (EC) No 1272/2008 (CLP) and UN-GHS.

Executive summary:

The objective of this study was to assess the acute inhalation toxicity of AUGEO SL 191 when administered to Wistar rats by a single four-hour nose-only inhalation exposure.

A sighting exposure was performed first, where a test atmosphere at 5 mg/L target concentration was tested on single animals of both sexes. No lethality was observed at this concentration. Thereafter the main study was also performed at 5 mg/L using five male and five female rats.

The animals were exposed to the test atmospheres for 4 hours using a nose-only exposure system. Aerosol concentrations and particle size distributions were checked at regular intervals during the 4-hour exposure. The days of exposures were designated as Day 0 and were followed by 14-day observation periods.

Clinical observations were performed on all animals during exposure at hourly intervals, following removal from restraint, approximately 1 hour after exposure, and daily for 14 days thereafter. Body weights were measured on Days 0 (before the exposure), 1, 3, 7 and 14. Gross necropsies were performed on all animals sacrificed on Day 14.

The mean achieved atmosphere concentrations in the study were 5.04 and 5.11 mg/L in the sighting and main study, respectively. The mass median aerodynamic diameters (MMAD) were 3.75 μm and 3.81 μm with geometric standard deviations (GSD) of 1.97 and 2.01 in the Sighting Group and the Main Group, respectively.

No mortality was noted during the study.

Laboured respiration (slight to moderate) was recorded in all animals of the study on Day 0.

Red-brown staining and/or wet fur were also observed in all study animals on Day 0. These observations were considered to be related to the restraint and exposure procedures and were considered not to be toxicologically significant. Each rat was symptom-free from Day 1.

In the sighting group, slight body weight loss was noted in both animals by Day 3, but thereafter, positive change was recorded in body weights. Both rats returned to their initial body weights by approximately Day 7.

In the main group, slight body weight loss was observed in 4 male and 2 female animals on Day 1 but no further body weight loss was noticed thereafter. All affected animals of this group normalised in the body weight by Day 3.

No internal or external findings were recorded at necropsy in any group.

Under the experimental conditions of this study, no mortality occurred in Wistar rats exposed to a test atmosphere concentration of 5.11 mg/L for 4 hours. The acute inhalation median lethal concentration (LC50) of AUGEO SL 191 in rats was therefore considered to be above 5.11 mg/L.

AUGEO SL 191 is non-toxic after acute inhalative administration and is therefore not classified according to Regulations (EC) No 1272/2008 (CLP) and UN-GHS.