Registration Dossier

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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
saturated atmosphere range 97.7 - 183.9 ppm
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
saturated atmosphere range 877 - 1759 mg/m³
Basis:
other: nominal conc. as calculated from range 0.877 - 1.759 mg/L
Remarks:
Doses / Concentrations:
saturated atmosphere range 8.8 - 23.7 ppm
Basis:
analytical conc.
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

open allclose all
Dose descriptor:
NOEC
Effect level:
>= 227 mg/m³ air (analytical)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: overall effects
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

Applicant's summary and conclusion