3,6,9-trioxaundecane-1,11-diol

Endpoint summary

Description of key information

There was no lethality noted in rats dosed orally with 16 ml/kg (~18,000 mg/kg) or rabbits dosed dermally with 16 ml/kg (~18000 mg/kg) tetraethylene glycol for 24 hours in most recent key studies. Mellon Institute UCC 1940 study arrived at lowest oral LD50 value of 30000 mg/kg bw that was used as the basis for LD50 value presented. Linkewise, dermal LD50 value of 20 ml/kg (~22600 mg/kg bw) derived by the UCC 1972 study was used as the basis for dermal LD50 value.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not specified but between 9 Dec 1985 and 6 April 1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The report does not specify about GLP/Guideline but sufficient data is available for interpretation of results

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Sprague-Dawley albino rats, weighing between 200 and 300 g were used. The rats are fasted overnight before dosing.

The animals are maintained on appropriate commercial diet and municipal water. Both are available ad libitum except during periods of fasting (rat peroral test) or manipulation.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The maximum dosage for the peroral test is 16 ml/kg. Based on the test results, no additional dose levels were examined.

Doses:

16 ml/kg

No. of animals per sex per dose:

5 males and 5 females.

Control animals:

not specified

Details on study design:

Animal weights are recorded at 0 days (before dose), 7 days and 14 days (just prior to sacrifice). At death or sacrifice, each animal is subjected to gross pathologic evaluation.

Statistics:

LD50's and the estimated LD50 slopes are calculated by the moving average method (Thompson, 1947; Weil, 1983) and are based on a 14-day observation period.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 16 mL/kg bw

Based on:

test mat.

Mortality:

None of 5 males or 5 females died from this dosage.

Clinical signs:

other: There were no signs of toxicity observed.

Gross pathology:

There were no remarkable gross pathologic lesions observed.

Other findings:

No additional information available.

No additional information available.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for male and female rats receiving single peroral doses of tetraethylene glycol was greater than 16.0 ml/kg (>18000 mg/kg).

Executive summary:

The acute oral toxicity of tetraethylene glycol was examined.

The LD50 for male and female rats receiving single peroral doses of tetraethylene glycol was greater than 16.0 ml/kg, Rats gained weight with no clinical signs of toxicity. There were no remarkable gross pathological lesions observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

30 000 mg/kg bw

Quality of whole database:

Although the database is quite old, the results demonstrate that lethality is observed only at very high doses.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not specified but between 9 Dec 1985 and 6 April 1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The report does not specify about GLP/Guideline but sufficient data is available for interpretation of results

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Sprague-Dawley albino rats, weighing between 200 and 300 g, were used.

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

The vapor is produced by passing air (at 2.5 liters/min) through the sample and then through a 9-liter animal chamber (dynamic conditions).

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

6 h

Concentrations:

Described as substantially saturated vapor generated at 24C.

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not specified

Details on study design:

Rats were weighed prior to exposure to the test material and again on day 7 and 14. Animals were observed for clinical symptoms and mortality. At the end of the 14 day observation period, a gross pathologic examination of the rats was conducted.

Statistics:

Body weight mean and S.D. were calculated.

Sex:

male/female

Dose descriptor:

LC0

Effect level:

0.06 ppm

Based on:

test mat.

Exp. duration:

6 h

Mortality:

No mortality was observed in males or females exposed to a substantially saturated vapor concentration.

Clinical signs:

other: No clinical signs were observed in males or females exposed to a substantially saturated vapor concentration.

Body weight:

Male rats gained weight on days 7 and 14 from pre-exposure values (Table 1). Females remained essentially the same throughout the 14 day observation period.

Gross pathology:

There were no treatment-related gross pathologic observations.

Other findings:

Using a vapor pressure of 0.0000465 mm Hg at 25C corresponds to a saturated vapor concentration of 0.061 ppm.

Table 1 Body weights of Males and Females exposed to a substantially saturated vapor concentration for 6 hours.

	Day 0	Day 7	Day 14
Males	237 + 2.4	261 + 5.7	282 + 7.9
Females	256 + 7.2	257 + 8.9	256 + 8.4

Conclusions:

A single dynamic inhalation exposure to substantially saturated vapor for a 6-hour period produced no deaths or other signs of toxicity among male and female rats.

Executive summary:

Groups of 5 male and 5 female rats were exposed to a substantially saturated vapor concentration for 6 hours. There were no effects on mortality, body weight, clinical symptoms or gross pathology noted in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

A saturated vapor is quite low, 0.061 ppm (0.49 ug/L) with no mortality noted.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not specified but between 9 Dec 1985 and 6 April 1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The report does not specify about GLP/Guideline but sufficient data is available for interpretation of results

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

New Zealand White rabbits, weighing between 2.0 and 3.0 kg, were used. The animals are maintained on appropriate commercial diet and municipal water.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Rabbits were subjected to 24 hours of contact with the test material which is retained under impervious sheeting on the clipped, intact skin of the trunk. As necessary for larger doses, gauze is wrapped around the trunk over the sample to prevent leakage. Vetrap® Bandaging Tape is wrapped over the impervious sheeting and the animal is returned to its cage for the contact period.

Duration of exposure:

24 hours

Doses:

16 ml/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not specified

Details on study design:

After the contact period, excess fluid is removed to diminish ingestion. Observations for skin reaction are made at one hour, 7 days and 14 days after the contact period. Five male and 5 females are included on each level used for the LD50 calculation. Animal weights are recorded at 0 days (before dose), 7 days and 14 days (just prior to sacrifice). At death or sacrifice, each animal is subjected to gross pathologic evaluation.

Statistics:

LD50's and the estimated LD50 slopes are calculated by the moving average method (Thompson, 1947; Weil, 1983) and are based on a 14-day observation period.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 16 mL/kg bw

Based on:

test mat.

Mortality:

There was no mortality noted in male or female rabbits exposed dermally to 16 ml/kg tetraethylene glycol for 24 hours.

Clinical signs:

other: In male rabbits ,sample residue and edema were observed at day 1. In females rabbits, sample residue, edema and erythema where observed on day 1.

Gross pathology:

There were no treatment related gross pathologic observations in male or female rabbits.

Other findings:

No additional information available.

Table 1 Male and female rabbit body weights following a 24 hour dermal exposure to tetraethylene glycol.

	Day 0	Day 7	Day 14
Males	2679 + 270	2743 + 342	2846 + 344
Females	2775 + 174	2820 + 204	3011 + 224

Interpretation of results:

GHS criteria not met

Conclusions:

Tetraethylene Glycol had an extremely low order of toxicity following single dermal application. LD50 was greater than 16ml/kg (>18000mg/kg).

Executive summary:

The acute dermal toxicity of tetraethylene glycol was examined using New Zealand White rabbits. Tetraethylene Glycol had an extremely low order of toxicity following single dermal application. LD50 was greater than 16ml/kg (>18000mg/kg).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

22 600 mg/kg bw

Quality of whole database:

Although the database is old, the results demonstrate that lethality is observed only at very high doses.

Additional information

There was no lethality noted in rats dosed orally with 16 ml/kg (~18,000 mg/kg) or rabbits dosed dermally with 16 ml/kg (~18000 mg/kg) tetraethylene glycol for 24 hours in most recent key studies. Mellon Institute UCC 1940 study arrived at lowest oral LD50 value of 30000 mg/kg bw that was used as the basis for LD50 value presented. Linkewise, dermal LD50 value of 20 ml/kg (~22600 mg/kg bw) derived by the UCC 1972 study was used as the basis for dermal LD50 value.

Justification for selection of acute toxicity – oral endpoint
Most recent study with acceptable experimental detail information included and performed in accordance to guidelines.

Justification for selection of acute toxicity – inhalation endpoint
Most recent study with acceptable experimental detail information included.

Justification for selection of acute toxicity – dermal endpoint
Most recent study with acceptable experimental detail information included.

Justification for classification or non-classification

Based on study data and low acute toxicity for oral, inhalation and dermal endpoints, the Classification according to GHS and the Directive 67/548/EEC (DSD) is not warranted.