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

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed publication

Data source

Reference

Reference 1

Reference Type:

publication

Title:

The Subchronic Inhalation Toxicity Of Polyethylene Glycol 200 In the Rats

Author:

J. W. Crook S. A. Thomson, J. To Weimer P. D. Hott R. L. Farrand, PhD A. Eo Cooper C. Lilly E. G. Cumminqs, D. H. Heitkamp

Year:

1980

Bibliographic source:

Army Armament Research And Development Command Aberdeen Proving Ground Md Chemical Systems Lab

Reference 2

Reference Type:

publication

Title:

Repeated dose inhalation toxicity study of the test chemical

Author:

Crook et al

Year:

1980

Bibliographic source:

Army Armament Research And Development Command Aberdeen Proving Ground Md Chemical Systems Lab

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Subchronic Inhalation Toxicity Of Polyethylene Glycol 200 In the Rats

GLP compliance:

not specified

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

Molecular formula:

(C2-H4-O)mult-H2-O

IUPAC Name:

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

Details on test material:

- Name of test material (as cited in study report): Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
- Substance type: Organic
- Physical state: Liquid

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-Source:Charles River Breeding Laboratories
- Weight at study initiation:115 gm and females approximately 77 gm

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

not specified

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:dynamic ~irflow chambers
- Method of holding animals in test chamber:
- Method of conditioning air:air conditioner
- System of generating particulates/aerosols:
- Temperature, humidity, pressure in air chamber:maintained at a constant level.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

6 hours a day, 5 days a week

Doses / concentrations

Remarks:

Doses / Concentrations:
100,1000 mg/m3
Basis:
nominal conc.

No. of animals per sex per dose:

216 rats

Control animals:

yes, sham-exposed

Details on study design:

No data

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data
- Time schedule:
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:

BODY WEIGHT: Yes
The .animals used in the PEG 200 study were .weighed individually at approximately 2-week intervals. The average weights for the various groups, i.e., males and females for the controls, low- and high-dose levels, were recorded.

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes

WATER CONSUMPTION: No data
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations:
- Dose groups that were examined:

HAEMATOLOGY: Yes
- Time schedule for collection of blood:
- Anaesthetic used for blood collection: Yes (identity) / No / No data
- Animals fasted: Yes / No / No data
- How many animals:
- Parameters checked in table [No.?] were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood:
- Animals fasted: Yes
- How many animals:
- Parameters checked in table [No.?] were examined.

URINALYSIS: No data
- Time schedule for collection of urine:
- Metabolism cages used for collection of urine: Yes / No / No data
- Animals fasted: Yes / No / No data
- Parameters checked in table [No.?] were examined.

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:

OTHER:

Sacrifice and pathology:

GROSS PATHOLOGY: Groups of male and female rats were euthanatized following 6 and 13 weeks of exposure to PEG 200 aerosol. Another group of rats and mice was euthanat ized 30 days after exposure to PEG 200. At termination and necropsy, tissues were evaluated grossly and preserved in 10% buffered formalin. The tissues were imbedded in paraffin and subsequently processed for staining with hematoxyl in and eosin. Tissues from the following were evaluated microscopically.

HISTOPATHOLOGY: Yes (see table) / No / No data

Other examinations:

Organ Weight:brain, eye, adrenal, thyroid, trachea, lung, turbinates, kidney, 1 iver, 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 weighed, and organ-to-body-weight ratios were calculated.

Statistics:

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

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

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:

not specified

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

-Toxic Signs. No obvious pattern of overt toxic signs was seen in the rat s or mi ce exposed to either 100 or 1000 mg/m3 of PEG 200. After each exposure, the fur of the animals exposed to the high dose appeared oi I y.

- MortaIity. None of the test rats died dur i ng the 13-week exposure or the 3D-day postexposure observation.

-Hematology and blood chemistry.
Hematology. During the 13-week exposure or the 3D-day postexposure period there were no consistently significant changes in red blood cell count, total and differential white blood cell count, hematocrit, or hemoglobin in the rats .

-Blood chemistry:There were no consistently 'significant changes in rat blood chemistry at the end of the 6- or 13-week exposures or the 30-day postexposure period.

-In male rats exposed for 13-weeks to the high dose, there appeared to be a slight decrease in the P-R interval in the EKG compared to the control animals. The usual abnormal ity associ ated with the P-P interval is an increase in duration, which indicates a slowing of the atrial conduction system. This interval will vary inversely with heart rate, but heart rate did not appear to he a factor in the present study. In any event, the decrease was not associated with any abnormality and may be considered inconsequential.

-PEG 20:did not product any adverse physiological effects on the rats exposed to the IOn and lnnn mg/m 3 concentrations for the various exposure periods

-Fischer 344 exposed rats, both males and females, showed no definite pattern as to weight loss or gain. At the end of the postexposure period the rats weighed as much as, or slightly greate than, the controls.

-Mild to moderate proliferative interstitial pneumonia was seen in nine rats, (three control males, five exposed males (two low- and three high-dose), and one female - low-dose. Acute to subacute i nf I ammat i on of the turb i nates was observed in one control female and two exposed (low-dose) males.

-Infiltration of foamy macrophages occurred in the lungs of one exposed (high-dose) male. Suppurative inflammation of the turbinates was seen in a contro I fema I e. A rena I cort i ca I cyst was found. in one control female no spontaneous deaths occurred

Effect levels

Dose descriptor:

NOAEC

Effect level:

1 000 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse toxicological, physiological, hematological, blood chemical, and pathological effects were observed.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The no observed adverse effect concentration (NOAEC) value of the test chemimcal in rats was observed at dose level of 1000 mg/m3.

Executive summary:

Rats were exposed to airborne concentrations of 100 mg/m3 and 1000 mg/m3 of test chemical for periods up to 13 weeks. Toxicological, physiological, hematological, blood chemical, and pathological effects were evaluated during the course of the exposures. No significant lesions observed in this study occurred exclusively in exposed animals and the severity of lesions which were found was not dose-related. The test chemical did not induced lesions in rat tissue at the dosage level and exposure/post exposure periods evaluated in this study. Organ:body weight ratios in rats at all concentrtions and for the 6- and 13-week exposure periods and the 30-day postexposure period showed no pattern of significance that could be related to test chemical. The mice organ:body weights for the 6-week·exposure period are unavailable. No pattern of significance could be related to test chemical exposure for the 13-week or the 30-day postexposure periods. The test chemical did not product any adverse physiological effects on the rats exposed to the 100 and 1000 mg/m 3 concentrations for the various exposure peri ods. This was not unexpected because the test chemical appear to present. There were no consistently 'significant changes in rat blood chemistry at the end of the 6- or 13-week exposures or the 30-day postexposure period. It appears that the test chemical produced no positive effects in the rodents at the 100 and 1000 mg/m3 test chemical concentrations over the 13 weeks of exposure used in this study. Thus it is concluded that the no observed adverse effect concentration (NOAEC) of the test chemical in rats was observed at dose level of 1000 mg/m3.

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