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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
Study period:
1987-04-13 to 1989-08-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study following internal Laboratory standards and protocols that are equivalent to OECD Guideline 403.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
The study followed a specific protocol (87-15-04-AI-A) and standard protocol amendment.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): dimethylaminoethoxyethanol (DMEE)
- Molecular formula: (CH3)2NCH2CH2OCH2CH2OH
- Molecular weight: 133.2
- Substance type: Pure active substance
- Physical state: Liquid, transparent, pale yellow
- Analytical purity: 97%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague-Dawley, Inc., Indianapolis, IN)
- Age at study initiation: 45 d (Static), 46 d (Dynamic bubbler), 51 d (Dynamic evaporator)
- Weight at study initiation: 174 g (Static mean weight- Male), 150 g (Static mean weight- Female), 186 g (Dynamic bubbler mean weight- Male), 152 g (Dynamic bubbler mean weight- Female), 210 g (Dynamic evaporator Mean weight- Male), 165 g (Dynamic evaporator Mean weight- Female)
- Fasting period before study: None
- Housing: Housed five per sex in 23.5 X 40 X 18 cm stainless steel wire-mesh cages on carriers
- Diet (e.g. ad libitum): Pelletted feed (Pro Lab RMH#3000, Agway, Inc.); ad libitum except during exposure
- Water (e.g. ad libitum): Tap water (Municipal Authority of Westmoreland County, Greenburg, PA); ad libitum except during exposure
- Acclimation period: yes, 2 days for static, 3 days for dyanmic bubbler, and 8 days for dynamic evaporator; the Study Director opinion was that the lower than 5-day acclimation period for the first two tests did not alter the interpretation of results.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 deg C
- Humidity (%): N/A
- Air changes (per hr): N/A
- Photoperiod (hrs dark / hrs light): 12-hr photoperiod throughout the entire study

IN-LIFE DATES: From: April 10 To: April 27 (Static), April 28 (Dynamic bubbler), May 3 (Dynamic evaporator).

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Static and dynamic bubbler exposures were in plexiglass and stainless steel chambers and the dynamic evaporator exposures were in glass and stainless steel chamber
- Exposure chamber volume: approximately 120 liters (static and dynamic bubbler exposures); 900 liters (dynamic evaporator exposures)
- Method of holding animals in test chamber: 5 per sex free to move in 26x18.5x18 cm wire-mesh cages for the static and dynamic bubbler exposure chambers; individually housed in 21x12.5x18 cm wire-mesh cages, free to move in the dynamic evaporator exposure chambers.
- Source and rate of air:
(A) For the static exposure, the test substance (120 grams untreated) was placed in an open tray at the top of the sealed 120-liter chamber and the vapor was allowed to achieve equilibration (17 hours). The animals were then placed into the chamber for a 4 hour exposure period.
(B) For the dynamic bubbler exposure, compressed air was passed through a 250 mL gas washing bottle containing approximately 59 grams of test substance. The air containing the test substance vapor entered directly into the exposure chamber at a rate of 30 L/min.
(C) For the dynamic evaporator exposure, the test substance was metered with a piston pump (Fluid Metering Inc., Oyster Bay, NY) into a heated evaporator. The resulting vapor mixture was carried to the chamber by a countercurrent air stream that entered the bottom of the evaporator at a rate of 200 L/min.
- Method of conditioning air: N/A
- System of generating particulates/aerosols: N/A
- Method of particle size determination: N/A
- Treatment of exhaust air: N/A
- Temperature, humidity, pressure in air chamber:
Static: 25 +/- 1 deg C, 77 +/- 23% % relative humidity
Dynamic bubble: 24 +/- 0 deg C, 37 +/- 2% relative humidity
Dynamic evaporator: 24 +/- 0 deg C, 43 +/- 2% relative humidity

TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of test substance in the exposure chamber atmosphere was determined for the dynamic and static exposures by sampling with XAD-2 sorbent tubes. The samples were desorbed and then analyzed by flame ionization gas chromatograpy.
- Samples taken from breathing zone: no

VEHICLE
- Composition of vehicle (if applicable): N/A
- 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: N/A

CLASS METHOD (if applicable)
Rationale for the selection of the starting concentration: The target concentration for both the static and dynamic exposures was the highest attainable vapor concentrations of the test substance without visual observation of an aerosol (saturated vapor).
Analytical verification of test atmosphere concentrations:
yes
Remarks:
The concentration of test substance in the exposure chamber atmosphere was determined for the dynamic and static exposures by sampling with XAD-2 sorbent tubes. The samples were desorbed and then analyzed by flame ionization gas chromatograpy.
Duration of exposure:
4 h
Concentrations:
Static: Mean 15 ppm, standard deviation +/- 8.11 ppm
Dynamic bubbler: Mean 72 ppm, standard deviation +/- 11.6 ppm
Dynamic evaporator: Mean 63 ppm, standard deviation +/- 3.4 ppm
No. of animals per sex per dose:
5 per sex per type of exposure (static, dynamic bubbler, or dynamic evaporator)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for signs of toxic effects on the day of exposure and daily following exposure for 14 days. The animals were weighed prior to exposure and on postexposure Days 7 and 14. The change in body weight was calculated by subtracting the pre-exposure value from each successive weight.
- Necropsy of survivors performed: Yes, a complete necropsy was performed for all animals. The survivors were anesthetized with methoxyflurane and killed by exsanguination via the branchial blood vessels. The lungs and liver for the female rat which died (static exposure) were extracted and fixed in 10% neutral buffered formalin.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: N/A
Statistics:
The mean and standard deviation of the body weights and body weight changes of the animals and the exposure concentrations, temperature, relative humidity and oxygen were calculated. No statistical comparisons were made.

Results and discussion

Preliminary study:
N/A
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 72 ppm
Based on:
test mat.
Remarks:
generated by dynamic bubbler
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 68 ppm
Based on:
test mat.
Remarks:
generated by dynamic evaporator
Mortality:
One delayed mortality was observed for female rats on postexposure Day 1. No other mortalities occurred during the study.
Clinical signs:
other: Static and dynamic bubbler: No clinical signs of toxicity were observed on the day of exposure or during the 14-day postexposure observation period. Dynamic evaporator: Blepharospasm and periocular wetness were the only clinical signs of toxicity observed
Body weight:
Mean body weight gain was observed for both sexes on postexposure Days 7 and 14.
Gross pathology:
Macroscopic lesions were not observed in animals sacrificed at the end of the 2-week postexposure period. The only macroscopic lesions observed was a dark red (mottled) discoloration of the lungs and liver, noted only in the rat which died.
Other findings:
N/A

Any other information on results incl. tables

The potential LC50 for male and female rats exposed to the test substance for 4 hours is > 72 ppm, which was the highest exposure concentration, obtained in the dynamic bubbler chamber.

For the static exposure, a decrease in concentration was observed with exposure time as the relative humidity rose during the exposure period. The decrease in concentration may be attributed to interaction of the test material with water (relative humidity), as the test substance is highly soluble in water. Similar interaction with water may have occurred during the dynamic exposures, as indicated by the low actual/nominal ratios of 0.42 and 0.66 for the test substance for the dynamic bubbler and dynamic evaporator exposures, respectively.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: not specified
Conclusions:
LC50 for male and female rats during the 4 hour exposure was > 72 ppm.