2,2'-(ethylenedioxy)diethanol

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Principles of method if other than guideline:

This study was performed to reveal any toxicological effects which might result from repeated long-term exposure to airborne concentrations of PEG 200.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated

EC Number:

500-038-2

EC Name:

Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated

Cas Number:

25322-68-3

IUPAC Name:

Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated

Test material form:

liquid

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male mice weighed approx. 30 mg and females approximately 25 mg. All animals were selected quarantined and examined. Mice were exposed in compartmented stainless-steel wire mesh cages. Each mouse cage compartment measured 3 in. x 2 in. x 2-1/4 in. The compartments were labeled with a number so that each animal was in the same cage and compartment for the daily exposures. Following the 6-hour exposure, the caged animals were removed from the chamber, placed on carts and carried to adjoining holding rooms. One room was for control and another room was for exposed animals. The animals were removed from the exposure cages and placed in individually labeled stainless steel mesh holding cages. Mouse holding cages measured 9-1/2 in. x 4 in. x 6 in. Food and water was available to the animals only while in the holding cages and not during exposures.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

Exposures were conducted in two 3000-liter dynamic flow stainless-steel chambers operated under negative pressure. Air was drawn into the system and the test substance aerosol was dispersed into the intake air and passed through collective protective filters before exiting into the atmosphere. Chamber design assured that the airborne concentration of the test substance was uniform. The chamber airflow was held constant throughout the test. The flow rate was used to calculate the nominal test substance concentration. Air pressure through the generators was adjusted to achieve the different test concentrations of the test substance.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

6 h/d, 5 d/wk

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.1 mg/L air (nominal)

Doses / concentrations 2

Dose / conc.:

1 mg/L air (nominal)

No. of animals per sex per dose:

A total of 90 mice were required, 30 to be exposed to the high dose level, 30 to the low dose level and 30 to serve as controls. Each of these groups were divided into three subgroups:
(a) 6-week exposure group of 10 animals
(b) 13-week exposure group of 10 animals
(c) a group of 10 animals to be held for 30 days after the 13-week exposure.

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

The animals were sex-segregated at all times. The exposed and control animals were observed daily for toxic signs and death. The animals used were weighed individually at approximately 2-week intervals.

Sacrifice and pathology:

Pathological and haematological examinations were performed on the respective groups at the termination of the exposure-holding periods. The animals were anesthetised with pentobarbital sodium and blood samples taken by cardiac puncture. Because of the small amount of blood obtainable for the mice, only hemograms were determined for this species. Groups of male and female mice were euthanatised following 6 and 13 weeks of exposure to the test substance aerosol. Another group was euthanatised 30 days after exposure to the test substance. At termination and necropsy, tissues were evaluated grossly and preserved in 10% buffered formalin. The tissues were embedded in paraffin and subsequently processed for staining with hematoxylin and eosin. Tissues from the following were evaluated microscopically: brain, eye, adrenal, thyroid, trachea, lung, turbinates, kidney, liver, spleen, heart, esophagus, stomach, small intestine, large intestine, pancreas, urinary bladder, testes, ovaries, and uterus. Before fixing the hearts, lungs, livers, kidneys and gonads, they were weight, and organ-to-body-weight ratios were calculated.

Statistics:

The data were compared statistically using an analysis of variance (ANOVA) which distinguish differences according to sex, exposure levek, and the effect of dose within sexes.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

No obvious pattern of overt toxic signs was seen. After each exposure, the fur of the animals exposed to the high dose appeared oily.

Mortality:

no mortality observed

Description (incidence):

No spontaneous deaths occurred.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

There was no definite pattern in the body weights of male or female mice. There were weeks when the average weights of the exposed animals were slightly less or greater than the control weights. Both male and female exposed mice weighed more than the controls during the 30-day post-exposure period.

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Description (incidence and severity):

There were no consistently significant changes in red blood cell count, total and differential white blood cell count, haematocrit, or haemoglobin.

Clinical biochemistry findings:

no effects observed

Description (incidence and severity):

No consistently significant changes in blood chemistry.

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

- 6 weeks: Interstitial pneumonia was found in 3 low dose mice (one male, two females). Atelectasis was observed in the lungs of a male and a female control. This probably reflects improper inflation during the necropsy procedure. Adrenal cortical degeneration was seen in a control female. Renal tubular vacuolar degeneration was seen in all of the male mice. Mild degenerative changes were observed in the liver of one female mouse exposed to the high dose. Cystic endometrial hyperplasia (minimal mild) was found in 10 females (5 controls, 5 exposed). One male control mouse died spontaneously at the end of 6 weeks. No significant microscopic lesions were found. There was a swollen area in the cervical region, probably due to accidental injury when the mouse was loaded into the cage.
- 13 weeks: Infiltration of foamy macrophages in the lung, a common incidental finding in rodents, was found in one exposed (low dose) male. Interstitial pneumonia occurred in 4 mice (2 males and 1 female control and 1 female - high dose). Renal tubular degeneration was again observed in all of the male mice. Cystic endometrial hyperplasia was noted in 10 females (5 controls - 4 low dose and 1 high dose). Endometriosis was found in 1 low dose mouse. occurred.
- 13 weeks exposure + 30-day post-exposure: Adrenal cortical degeneration was found in 1 exposed (low dose) female. Interstitial pneumonia occurred in 4 males (1 control, 2 low, 1 high dose). Infiltration of foamy macrophages was seen in the lung of 1 exposed (high dose) male. Tubular degeneration was identified in all males. Endometrial cysts were found in 12 females (5 controls, 4 low, 3 high dose). Hydronephrosis was found in 1 exposed (high dose) male.

Histopathological findings: neoplastic:

no effects observed

Effect levels

Dose descriptor:

NOAEC

Effect level:

1 mg/L air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects

Target system / organ toxicity

Critical effects observed:

no