2,2'-[ethane-1,2-diylbis(oxy)]bisethyl diacetate

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented study report which meets basic scientific principles. Lack of details on study design and test material.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

yes

Remarks:

lack of details on study design and test material

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-[ethane-1,2-diylbis(oxy)]bisethyl diacetate

EC Number:

203-846-0

EC Name:

2,2'-[ethane-1,2-diylbis(oxy)]bisethyl diacetate

Cas Number:

111-21-7

Molecular formula:

C10H18O6

IUPAC Name:

2-[2-(2-acetyloxyethoxy)ethoxy]ethyl acetate

Details on test material:

- Name of test material (as cited in study report): Triethylene glycol diacetate
- Analytical purity: no data
- Physical state: liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: A&E Farms, Altamont, USA
- Diet: Purina Laboratory Chow, either ground or pelleted

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical glass inhalation chambers
- Source and rate of air: filtered air at 1 L/min through a 125 mL gas washing bottle fitted with a fritted cylinder and partially filled with the compound.
- System of generating vapour: The fritted cylinder broke up the air stream into small bubbles which rose through the column of the test material and assisted in vaporising the compound into the air stream. The gas washing bottle was placed in a water bath heated to 100 °C. The effluent air from the gas washing bottle was passed directly into the inhalation chamber.

TEST ATMOSPHERE
- Brief description of analytical method used: Samples were taken in methanol each day and analyzed by gas chromatography.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Concentrations were calculated on the basis of air flow and weight loss of compound and gas chromatography of air samples.

Duration of treatment / exposure:

29 days

Frequency of treatment:

6 h/day, 5 days/week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
saturated atmosphere range 97.7 - 183.9 ppm
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
saturated atmosphere range 877 - 1759 mg/m³
Basis:
other: nominal conc. as calculated from range 0.877 - 1.759 mg/L

Doses / concentrations 3

Remarks:

Doses / Concentrations:
saturated atmosphere range 8.8 - 23.7 ppm
Basis:
analytical conc.

Doses / concentrations 4

Remarks:

Doses / Concentrations:
saturated atmosphere range 80 - 227 mg/m³
Basis:
other: analytical conc. as calculated from range 0.08 - 0.227 mg/L

No. of animals per sex per dose:

6

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

BODY WEIGHT: Yes

HAEMATOLOGY: Yes
- Time schedule for collection of blood: prior to the first exposure and following the 20th exposure
- Parameters checked: haemoglobin, cell volume, white cell count and differential

Sacrifice and pathology:

GROSS PATHOLOGY: Yes. Liver, kidneys, spleen, heart, brain, lungs and testes.
HISTOPATHOLOGY: Yes. Trachea, lung, heart, tongue, oesophagus, stomach, small and large intestine, liver, kidney, urinary bladder, pituitary, adrenal, pancreas, thyroid, parathyroid, testes, ovary and uterus, spleen, femoral bone marrow, cerebrum, cerebellum and eye.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

slight lacrimation and yellow tinged fur (non adverse)

Mortality:

mortality observed, treatment-related

Description (incidence):

slight lacrimation and yellow tinged fur (non adverse)

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

treatment group: slighlty impaired BW gain

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Details on results:

CLINICAL SIGNS AND MORTALITY
No animals died during the study period. Slight lacrimation in the treatment and control group was observed throughout each exposure and on the seventh exposure it was noted that the experimental animals´ fur was becoming tinged with yellow.

BODY WEIGHT AND WEIGHT GAIN
Body weight gain in the treatment group was slightly reduced in comparison to the control group.

HAEMATOLOGY
No effects on haematological parameter observed.

GROSS PATHOLOGY
No gross lesions at necropsy in all animals. No evidence was seen of irritant effects on the upper respiratory tract, eyes or nose.

HISTOPATHOLOGY
The experimental and control groups showed the common chronic murine pneumonitis and both groups seemed to be equally affected. There was no evidence of chemical pneumonitis nor of the presence of any unabsorbed foreign substance in the alveoli.

OTHER FINDINGS
The analytical concentrations were about ten times lower than the calculated concentrations. Therefore, 26 g of hair of the test animals was analysed and 23.8 mg of the test compound could be extracted.

Effect levels

1

Dose descriptor:

NOEC

Effect level:

>= 227 mg/m³ air (analytical)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: overall effects

2

Dose descriptor:

NOEC

Effect level:

>= 23.7 ppm (analytical)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: overall effects

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1. Results of haematology (mean out of 6 animals).

	Haemoglobin	Cell volume	White blood cell count
Pre-exposure
Treatment group	15.8	49.3	18.48
Control group	15.4	49.3	23.97
Post-exposure
Treatment group	19.2	49.2	21.92
Control group	19.5	50.2	24.53

Table 2. Chamber concentrations.

Method	Range [ppm]	Mean [ppm]	Standard deviation	Number of observations
Calculated weight loss and air flow	91.7-183.9	137.7	26.4	22
Gas chromatography of air samples	8.8-23.7	*	3.6	27

*: unreadable in study report