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Toxicological information

Acute Toxicity: inhalation

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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: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test article name: Dimethyl sulfoxide
Source: Elf aquitaine Production
Batch no. : 97-097
Purity: 99.88%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sprague-Dawley, Charles River UK Ltd, anston Road, argate, Kent, UK
- Age at study initiation: 8-9 weeks old
- Weight at study initiation: 210-245 g (males) and 185-211 g (females)
- Fasting period before study:
- Housing: by sex in group of 5 in wire-wesh cages
- Diet (e.g. ad libitum): SDS RM1 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/-2
- Humidity (%): 55+/-10
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To: no data

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The vapour generator was designed to produce and maintain an atmosphere containing the vapour of DMSO at the saturation concentration in air by evaporation of the test substance from a fritted glass disc with a countercurrent of air. The test substance was delivered to the generator at a constant flow rate from a syringe driven by a syringe pump and the air supplied to the generator was dried, filtered and oil free.

The snout-only exposure chambers (ADG Developments ) used for the exposures were of cylindrical form (30 cm i.d., 45 cm height) and made of aluminium alloy.  The chambers have an enclosed volume of approximately 30 litres. The rats were held for exposure in moulded polycarbonate restraining tubes which were attached at evenly spaced ports in the cylindrical section of the chamber, and were designed to allow only the snout to project into the  chamber. Each rat was restrained in a forward position by an adjustable foamed plastic stopper which also provided a seal for the tube.

Rats were held for exposure in nose-only molded polycarbonate restraining tubes which were attached to a central exposure chamber. 

The test atmosphere entered through a port at the top centre of the chamber and passed out through a port at the base section below the level of the rats. Each chamber was positioned in a large cabinet equipped with an extract fan exhausting to atmosphere through an absolute filter.

TEST ATMOSPHERE
- Brief description of analytical method used: At least five air samples were taken from the chamber during the exposure to determine the concentration of test substance in the air chamber. The samples were taken at approximately 30, 60, 95, 120, 180,  and 230 minutes alter the start of exposure. 
Each air sample was withdrawn, at 2 liters per minute, into a gas absorption trap (gas bubbler) containing 2-butanone as the trapping solvent. The volume of the air sample was measured with a wet-type gas meter.
Two additional air samples were taken during the Group 3 exposure using a May impinger.

The May impinger is used for particle size distribution analysis of droplet aerosol atmospheres. The device has a three stage particle size discrimination and is intended to simulate some of the characteristics if the respiratory tract, where similar processes of inertial collection of particles operate. At a constant flow rate of 10 liters per minute the particles are distributed between the stages according to equivalent aerodynamic diameter (EAD) as follows (the approximate size ranges for which collection efficiencies exceed 10% are shown):

Chamber 1 4 µm and above (50% cut-off EAD approximately 6 µm)
Chamber 2 remainder down to 2 µm (50% cut-off EAD approximately 3 µm)
Chamber 3 remainder down to 0.5 !am (50% cut-off EAD approximately 1 µm)


5 minutes if the theoretical time required for the concentration of the aerosol in the chamber to reach 90% of its final value under the conditions of the exposure employed May, K.R., Multistage Liquid Impingers., Bacteriol: Rev. 30, 1966, 559-570

- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0, 0.9 and 5.33 mg/l
No. of animals per sex per dose:
5 males and 5 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were observed continuously for reaction to the test atmosphere during exposure, at one and two hours after exposure, and at least twice daily during the post-exposure interval. Body weight, food and water consumption were measured daily for all rats, from day of delivery until the end of the observation interval.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Rats were sacrificed and subjected to a detailed macroscopic examination at the end of the 14-day observation interval. Lungs were processed and examined microscopically.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC0
Effect level:
> 5.33 mg/L air
Exp. duration:
4 h
Remarks on result:
other: No mortality and clinical sings
Mortality:
There were no deaths during or following exposure to DMSO.
Clinical signs:
There were no clinical signs related to exposure to DMSO during exposure. Soiling of the fur with excreta, as a consequence of the method of restraint, was seen in all test and control rats during and immediately after exposure.
Normal appearance and behavior was observed in all animals during the 14-day observation interval.
Body weight:
Rate of body weight gain, and food and water consumption in rats exposed to DMSO were similar to controls.
Gross pathology:
There were no macroscopic abnormalities in test or control rats.
Other findings:
- Organ weights: Lung to body weight ratios in test animals were similar to controls
- Histopathology: There were no treatment-related histopathologic changes in the  lungs of test animals that could be ascribed to DMSO exposure. Only minor changes were reported and these of similar incidence in control and test rats : foamy alveolar macrophages (10/10 in high dose, 4/5M and 3/5 F in mid dose group, 4/5M & 5/5F in controls)

- Other observations: The analyzed concentration of DMSO in the exposure chamber during exposure was 5.33 mg/l (sd 0.475 mg/l). Analysis of aerosol determined that 32% of the particles were less than 4 microns in size, and 20% were less than 0.5 microns. The remainder were greater than 4 microns. The respirable fraction of DMSO in the test aerosol was 52%.

Any other information on results incl. tables

Concentration of DMSO

The mean analyzed concentrations of DMSO in the chamber air, the standard deviation (sd) of the means and the nominal concentrations were:

Group Analyzed          sd            Nominal

concentration             concentration

           (mg/l)              (mg/l)

2           0.90             0.043            2.9

3          5.33             0.475            35.6

The nominal concentration was calculated from the amount of DMSO dispersed and the total volume of air supplied to the exposure system.

Chamber air temperature and relative humidity

The mean chamber air temperature, the relative humidity and the standard deviation (sd) of the means during exposure of the groups were:

Group            Temperature      Relative Humidity

             (°C)             (°/U)

Mean   sd            Mean            sd

1 (Control)             22            0.3            48            1.2

2 (0.90 mg/1)            22            0.3            48            2.3

3 (5.33 mg/1)            24            0.4            41            4.8

There were no extremes of chamber air temperature or relative humidity considered likely to have influenced the results of the study.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
Under these experimental conditions, the LC0 of DMSO was higher than 5.3 mg/l in Sprague Dawley rats exposed nose-only for a 4-hour period.
Executive summary:

The acute inhalation toxicity of DMSO was evaluated in a 4-hour, single-exposure study in rats according to OECD Guideline 403 (May 12th 1981). DMSO was initially administered to a single group of five male and five female Sprague Dawley rats via nose only vapor exposure at concentrations of 0, 0.9 or 5.33 mg/l. Rats were held for exposure in nose-only molded polycarbonate restraining tubes which were attached to a central exposure chamber.

Rats were observed continuously for reaction to the test atmosphere during exposure, at one and two hour after exposure, and at least twice daily during the post-exposure interval. Body weight, and food and water consumption were measured daily for all rats, from day of delivery until the end of the observation interval. Rats were sacrificed and subjected to a detailed macroscopic examination at the end of the 14-day observation interval. Lungs were processed and examined microscopically.

There were no deaths during or following exposure to DMSO.

There were no clinical signs related to exposure to DMSO during exposure. Soiling of the fur with excreta, as a consequence of the method of restraint, was seen in all test and control rats during and immediately after exposure. Normal appearance and behaviour was observed in all animals during the 14-day observation interval

Rate of body weight gain, and food and water consumption in rats exposed to DMSO were similar to controls. There were no macroscopic abnormalities in test or control rats.

Based on the results of this study, the LC0 of DMSO was higher than 5.3 mg/l when male and female Sprague Dawley rats were exposed nose-only to a vapor of the test article for a single, 4-hour period.