2,2'-(ethylenedioxy)diethanol

Endpoint summary

Description of key information

An oral LD50 was determined to be > 16 mL/kg bw (18080 mg/kg bw).

The dermal LD50 for rabbits was determined to be > 16 mL/kg bw (18080 mg/kg bw).

The inhalation LC50 for rats was determined to be > 5.2 mg/L.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Principles of method if other than guideline:

Five Sprague-Dawley rats per sex per dose were exposed to the test substance via oral gavage at a dose level of 16 mL/kg bw (equivalent to 18080 mg/kg bw). After an observation period of 14 days animals were necropsied.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Batch no.: TS-3200424
- Appearance: Colorless, transparent viscous liquid
- Purity: 99.82%

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200-300 g
- Fasting period before study: The rats are fasted overnight before dosing.
- Diet: commerical diet (ad libitum)
- Water: municipal water (ad libitum)

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

The animals receive the test material by stomach intubation with a ball-end stainless steel needle. The sample is injected trough the needle by means of a syringe and doses are varied by adjusting the volume of the test material or its dilution.

Doses:

16 mL/kg

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

5 males and 5 females are included on each level used for the LD50 calculation. LD50 and the estimated LD50 slopes are calculated by the moving average method and are based on a 14-day observation period. Animals 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:

no data

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 16 mL/kg bw

Based on:

test mat.

Remarks on result:

other: Equivalent to 18080 mg/kg bw

Mortality:

none

Clinical signs:

other: sluggishness, unsteady gait

Gross pathology:

no remarkable gross lesions

Signs of toxicity included sluggishness and an unsteady gait. Recovery occurred at 3 hours to 1 day. There were no remarkable gross lesions evident at necropsy.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

18 080 mg/kg bw

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

no guideline followed

Principles of method if other than guideline:

Followed the specific protocol and standard protocol amendment by the Bushy Run Research Center. Five Sprague-Dawley rats per sex per dose were exposed to the aerolised test substance via a whole body inhalation system. They were exposed to a dose of 5.2 mg/L air for 4 hours. After an observation period of 14 days animals wer necropsied.

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

yes

Specific details on test material used for the study:

- Source: Union Carbide Chemicals and Plastics Company Inc., Texas City, TX
- Purity: ≥ 99.7%

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague-Dawley Inc., Indianapolis, IN
- Housing: Rats were housed 5 per sex in stainless steel, wire-mesh cages in 2 rooms for the prestudy quarantine and postexposure periods, respectively. During exposure, rats were housed individually in 21 x 12.5 x 18 cm wire-mesh cages and exposed in a 1300-liter Plexiglas and stainless steel chamber
- Diet: Pelletal feed (Pro Lab RMH #3000, Agway, Inc.), ad libitum, except during exposure
- Water: tap water, ad libitum, except during exposure

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23 °C
- Humidity: 40-56%
- Photoperiod: 12/12 h

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

5.54 µm

Geometric standard deviation (GSD):

2.71

Remark on MMAD/GSD:

MMAD 95% confidence interval were 4.72 - 6.50 µm

Details on inhalation exposure:

The test substance was metered from a piston pump (Fluid Metering Inc., Oyster Bay, NY) into an atomizer (Spraying Systems Co., Wheaton, IL) fitted with a No. 1650 liquid nozzle and a No. 64 air nozzle. The atomizer was positioned in the top of the inhalation chamber turret where the liquid diluted to the desired concentration and dispersed throughout the chamber by filtered supply air.
The target concentration for the exposure was 5 mg/L, based on the guidelines for "limit" testing met forth by the Toxic Substances Control Act (TSCA). A particle size lower than an MMAD of 5.3 µm could not be produced without greatly reducing the aerosol concentration of the test substance.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.2 mg/L air

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Animals were observed for signs of toxic effects on the day of exposure and daily following exposure. The animals were weighed prior to exposure and postexposure Days 7 and 14. The change in body weight was calculated by subtracting the pre-exposure values from each successive weight. A complete necropsy was performed for all animals. The survivors were anaesthesized with methoxyflurane and killed by exsanguination via the brachial blood vessels. No tissues were saved.

Statistics:

The mean and standard deviation of the body weights, body weight changes, and exposure concentrations were calculated. No statistical comparisons were made.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.2 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality was observed.

Clinical signs:

other: Periocular wetness, blepharospasm wet (oily fur), absence of toe and tail pinch reflexes. Unkempt fur was the only sign observed during the post-exposure period.

Gross pathology:

No macroscopic lesions were observed in animals sacrificed at the end of the 2-week post-exposure period.

A mean (+/- SD) of the test substance concentration of 5.23 (±0.15) mg/L was obtained. The nominal concentration was 19.3 mg/L.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5 200 mg/m³ air

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Principles of method if other than guideline:

Five New Zealand White rabbits per sex per dose were received a dermal application of 16.0 mL/kg bw. This was held into place for 24 hours under occlusive dressing. After the contact period, excess fluid is removed to diminish ingestion. After an observation period of 14 days animals the LD50 was determined.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Batch no.: TS-3200424
- Appearance: Colorless, transparent viscous liquid
- Purity: 99.82%

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.0-3.0 kg
- Diet: commerical diet (ad libitum)
- Water: municipal water (ad libitum)

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

Animals are subjected to 24 hours of contact with the test substance 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. Doses are varied by adjusting the volume or weight of the test material. Solids are dosed as powders and are moistened with a sufficient amount of water or other suitable vehicle to form a paste. After the contact period, excess fluid is removed to diminish ingestion.

Duration of exposure:

24 hours

Doses:

16.0 mL/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

Observations for skin reaction are made at one hour, 7 days and 14 days after the contact period. 5 males and 5 females are included on each level used for the LD50 calculation.

Statistics:

no data

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

16 mL/kg bw

Based on:

test mat.

Remarks on result:

other: Effect value equivalent to 18080 mg/kg bw

Mortality:

- males: 0/5
- females:1/5

Clinical signs:

other: There were no cutaneous effects observed on any animal during the observation period. The only abnormal signs noted were emaciation (in one female) and abdominal distention (in 2 females)

Gross pathology:

Necropsy of the animal that died revealed gas-filled intestines.

None of 5 male rabbits died from 16.0 mL/kg. One of 5 females died from this dose. There were no cutaneous effects observed on any animal during the observation period. The only abnormal signs noted were emaciation (in one female) and abdominal distention (in 2 females). One female rabbit died at 6 days. Necropsy of the animal that died revealed gas-filled intestines. The afore-mentioned signs, the one death and the necropsy findings could be attributable to a spontaneous intestinal disorder often observed in this species rather than to chemical toxicity. Gross pathologic evaluation of survivors revealed tan lungs (of one female), liquid-filled stomach and intestines (one female) and slight vascularization of the treated skin (one male).

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

18 080 mg/kg bw

Additional information

An acute oral LD50 value of > 16 mL/kg bw (18080 mg/kg bw) for male and female rats was reported. Clinical signs observed were sluggishness and unsteady gait. Recovery occurred 3 hours to 1 day. There were no remarkable gross lesions evident at necropsy. No mortalities were seen (BRRC, 1990).

In a GLP-compliant acute inhalation study performed with Sprague-Dawley rats, 5 male and 5 female animals were exposed whole body to an aerosol of 5.4 mg/L. No mortalities were reported. Clinical signs found were periocular wetness, blepharospasm wet (oily) fur, absence of toe and tail pinch reflexes. Unkempt fur was the only sign observed during the post-exposure period. No macroscopic lesions were observed in animals sacrificed at the end of the 2-week post-exposure period. The acute inhalative LC50 value was found to be > 5.2 mg/L for 4 hours. (BRRC, 1991).

An acute dermal LD50 value of > 16 mL/kg bw (18080 mg/kg bw) was reported for male and female rabbits. The test substance was given to the intact skin of the trunk. One female animal died; no cutaneous effects were observed on any animal during the observation period. The only abnormal signs noted were emaciation in one female and abdominal distention in 2 females (BRRC, 1990).

Justification for classification or non-classification

The available experimental animal data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on the available information classification for acute toxicity is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. (EC) 1272/2008.