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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study undertaken at GLP accredited laboratory to internationally accepted guidelines. The restriction is due to the use of read across approach: the study was performed not with DEGDEE but with DEGEE, a substance which like DEGDEE is part of the diethylene glycol monoalkyl and dialkyl ethers category. These substances have been demonstrated to be similar in structure, physical/chemical properties and toxicological profile.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

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:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report):Diethylene glycol monoethyl ether (DGME)
- Molecular formula (if other than submission substance): C6H14O3
- Molecular weight (if other than submission substance): 134.2
- Substance type: Organic
- Physical state: Liquid
- Analytical purity: 98.1
- Main Impurities: ethylene glycol 1.4%, ethylglycol 0.26%
- Lot/batch No.:3641/ 85472
- Storage condition of test material: Room temperature and humidity in a fume cupboard.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: UK
- Age at study initiation: approximately 6 weeks
- Weight at study initiation: group mean bodyweights (g) was between 135.4 and 169.0
- Fasting period before study:
- Housing: The animals were housed and exposed in a single room. The rats were kept 5 of the same sex to a cage, suspended on a movable rack.
Each cage had stainless steel mesh front, back and floor and stainless steel sides. The dimensions were 53 cm long, 35 em wide and 25 cm high. Plastic trays lined with absorbent paper, were placed below the cages to collect the animal excreta. The paper was changed daily.
- Diet (e.g. ad libitum): standard quality controlled laboratory rat food
- Water (e.g. ad libitum): tap water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5- 23.0
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12hrs dark and 12 hr light

IN-LIFE DATES: From: 21 November 1990 (animals arrived) To: 17 December 1990 (terminal kill Group 3)

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: ADG snout-only inhalation chamber (with 20 exposure ports)

- Exposure chamber volume:approximately 50 litres.

- Chamber temperature: 22°C (mean)

- Method of holding animals in test chamber: push rod in tapered chamber


- Source and rate of air: Air was withdrawn from the base of the chamber at a rate of 30 litres per minute. The air was withdrawn by a vacuum pump through filtration media, to remove particulate and silica gel to remove excess moisture.
The extract and inlet air supplies were balanced by allowing air to be drawn through a Cambridge filter, into the tangential inlet duct at the top of the chamber.

- Pressure in air chamber: 10 l/min, which corresponded to an inlet pressure of 86 psig

TEST ATMOSPHERE
- Brief description of analytical method used: The test substance was metered from an all polypropylene disposable syringe
mounted on an infusion pump, via a PTFE tube, to a stainless steel concentric jet atomiser. The atomiser was set into the base
of an aluminium and glass elutriation column.
Clean, dried compressed air was supplied to the atomiser at 10 litres per minute. The test substance aerosol was introduced into the elutriation column where it was mixed with diluent air introduced at a rate of 15 litres per minute. The aerosol laden air pased into the exposure chamber.

- Particle size distribution: Two samples taken during exposure period. Analysis using a Marple 296 cascade impactor at a rate of 2 l/min. Exposure mean less than 6um aerodynamic diameter: Low concentration 96.5%, high concentration 92.1%.

- MMAD (Mass median aerodynamic diameter) Low concentration: 4.153, high concentration 3.855 um.


Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
1. (Air control) air only
2. (Test) 3.73
3. (Test) 5.24
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed continuously throughout exposure for signs of
reaction to the test substance and at least twice daily throughout the 14-day observation period. All rats were weihgt daily from the day of arrival up to and including the day of death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,food consumption, water consumption

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.24 mg/L air
Based on:
test mat.
Remarks on result:
other: aerosol exposure
Mortality:
There were no deaths during the study.
Clinical signs:
There were no signs related to exposure to DGME.
Body weight:
There were no treatment-related differences.
Gross pathology:
Macroscopic pathology: Pale, raised areas were seen on the lungs of 3/5 males and 1/5 females exposed to 5.24 mg/l. Dark spots were seen on the lungs of 1/5 males exposed to 5.24 mg/l.
Microscopic pathology: Minimal centrilobular hepatocyte enlargement in 3/5 males exposed to 5.24 mg/l.
Other findings:
- Lung weight to bodyweight ratios: All ratios are considered to be within normal limits.
- Water consumption: There were no treatment-related differences.
- Food consumption: There were no treatment-related differences.
- Histopathology: High dose group: minimal centrilobular hepatocyte enlargement in 3/5 males. The authors of the study considered this to be related to exposure and speculated that it may indicate a work hypertrophy. Low dose group: no significant observations.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LC50 for Diethylene glycol ethyl ether when exposed to aerosols was found to be >5.24mg/l in rats.
Executive summary:

DEGDEE and DEGEE, which is in the above study tested for its acute inhalation toxicity in rats, are both part of the diethylene glycol monoalkyl and dialkyl ethers category described and evaluated in the document titled "Category Approach-Read across Bis(2 -ethoxyethyl)ether" (2013).

These substances have been demonstrated to be very similar in structure, physical/chemical properties and toxicological profile . Therefore, a read-across from DEGDEE to data obtained with DEGEE is scientifically justified.