Reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-d

Endpoint summary

Description of key information

Data on the components of the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol, triethylene glycol (TEG) and tetraethylene glycol (TTEG), and the similar mixture Crude Penta, which contains 55.32% w/w TTEG and 29.82% w/w pentaethylene glycol (PentaEG), were used to assess its acute toxicity potential.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

February 3, 1994 - February 17, 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Justification for type of information:

This substance is another reaction mass of ethylene glycols that is similar but not identical to the Reaction mass of 2,2’-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol. Because of the same constituents, it is considered appropriate to read across.

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

Test substance was administered, as received, by stomach intubation to male and female rats. Animals were observed fro 14 days after dosing and necropsied.

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

A 1-quart container of Crude Penta (gross weight: 1418.2 g), Lot No. TS-2561109, CAS No. 25322-68-3, was received on November 11, 1993, from UCC, Texas City, TX, and assigned BRRC Sample No. 56-411. The test substance was a black, slightly viscous liquid. It was stored at room temperature.

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female Sprague Dawley. albino rats were received from Harlan Sprague Dawley, Inc. (Indianapolis, IN). The strain and species were selected because of their availability and existing historical data. Male rats were ordered to be approximately 195 to 215 g (designated by the supplier to be approximately 7 to 8 weeks of age). Female rats were ordered to be approximately 220 to 240 g (approximately 11 to 12 weeks of age). The females were ordered to be nulliparous and nonpregnant. Routinely, male and female rats that were ordered in at 6 weeks of age (initially received for other acute testing) were used as long as weight requirements were met on the day of dosing.

All animals were housed in Room 109 upon receipt. For the peroral test, the rats remained in Room 109 until the termination of the study. Approximately once every 3 months, 5 rats/sex received for acute testing and housed in Room 109 were subjected to adquality control evaluation, including gross pathology, parasitology and viral serology testing. Periodically, a clinical veterinarian examined the rats housed in Room 109 for any signs of health deficiencies. All animals were assigned a unique number and identified by cage cards. Animals were also identified by an ear tagging procedure during the week of receipt.

The animals were separated by sex and group housed (up to 5/cage) in stainless steel, wire mesh cages (approximately 30.5 x 31.0 x 18.0 cm.). DACB (Deotized Animal Cage Board; Shepherd Specialty Papers, Inc.) was placed under each cage and changed regularly. An automatic timer was set to provide fluorescent lighting for a 12-hour photoperiod (approximately 0500 to 1700 hours for the light phase). Temperature and relative humidity were recorded (Cole-Parmer Hygrothermograph* Seven-Day Continuous Recorder, Model No. 8368-00, Cole-Parmer Instrument Co., Chicago, IL). Temperature was routinely maintained at 66-77OF during the test period; relative humidity was routinely maintained at 40-708. Any minor exceptions to these specified ranges can be found in the raw data.

Tap water (Municipal Authority of Westmoreland County, Greensburg, PA) was available ad libitum except during dosing and was delivered by an automatic watering system with demand control valves mounted on each rack. Water analyses were provided by the supplier and Chester Lab and RJ Lee Group, Inc. at regular intervals. EPA standards for maximum levels of contaminants were not exceeded. Pelleted, certified AGWAY* PROLAB* Animal Diet Rat, Mouse, Hamster 3000 (Agway Inc.) was available ad libitum. For the peroral test, the feed was removed the day before dose administration. After dosing, feed was again made available ad libitum. Analyses for chemical composition and possible contaminants of each feed lot were performed by Agway Inc. and the results are included in BRRC files. Feed and water analysis reports were reviewed by the Study Director as they were available.

The animals were acclimated for at least 5 days before dosing. Clinical observations were conducted twice, at the time of receipt and during animal identification and/or dosing. Cage-side observations and mortality checks were conducted at least once daily. Animals considered unacceptable for the study, based on the clinical signs or body weights, were rejected for use on this study.

Rat body weights were within f 20% of the group mean for each sex. For the peroral test, the body weight range on the day of dosing was 281 to 295 g for males and 208 to 246 g for females (including 2 females used for preliminary/range-finding testing). A total of 5 male and 5 female rats were used for the peroral test.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test substance was dosed as received for the peroral test. All doses were administered by stomach intubation through a commercial 16-gauge (3-inch) ball-end stainless steel needle attached to a disposable syringe. The exact amount of the test substance given to each rat was recorded on the raw data form.

Doses:

16 g/kg

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

The rats were fasted overnight before dosing. Two female rats were first included in preliminary/range-finding testing. For the definitive study, 5 male and 5 female rats were dosed with 16.0 g/kg of the undiluted test substance (the maximum required dose - limit test). For individual animals, the dosing volume was adjusted according to body weight. Dosed rats were observed frequently for signs of toxicity on the first day of the test and twice a day theteafter (except on weekends or holidays when they were examined for death alone). Weights were recorded on the day of dosing and at 7 and 14 days after dosing.

After 14 days, all rats were anesthetized with halothane and killed by exsanguination following severance of the brachial vessels. Necropsies were performed on all animals. The following tissues were collected from selected animals and retained in 10% neutral buffered formalin: kidneys, urinary bladder, liver, sciatic nerve, stomach, intestines and spleen.

Preliminary study:

In preliminary/range-finding testing, 1 female rat was dosed with 4.0 ml/kg of Crude Penta (as received) and another was dosed with 16.0 ml/kg: both survived.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 16 000 mg/kg bw

Based on:

test mat.

Mortality:

In the definitive peroral test, 16.0 g/kg of undiluted Crude Penta killed 0 of 5 male and 0 of 5 female rats.

Clinical signs:

other: The only signs of toxicity observed were a brown stain on the perianal fur in several animals (4 male, 3 female) and a trace amount of blood in the urine of 1 female (positive by HEMASTIX Reagent Strips). Affected rats recovered within 4 days.

Gross pathology:

At necropsy, 2 male rats had a trace amount of blood in the urine (positive by HEMASTIX Reagent Strips). The left testicle of another male rat was smaller than normal. There were no gross lesions apparent in females at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

No mortality was observed in five male and five female Sprague-Dawley rats exposed to 16 g/kg Crude Penta by peroral intubation.

Executive summary:

No mortality was observed in five male and five female Sprague-Dawley rats exposed to 16 g/kg Crude Penta by peroral intubation.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

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

Justification for type of information:

Read across is based on the category approach. Please refer to attached category document.

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.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: basic information given

Justification for type of information:

Read across is based on the category approach. Please refer to attached category document.

Principles of method if other than guideline:

LD50 calculation

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

other: intubation

Vehicle:

not specified

Details on oral exposure:

Rats, weighing between 200 and 300 g, 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.
The rats are fasted overnight before dosing. 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.

Doses:

16 ml/kg

No. of animals per sex per dose:

5

Control animals:

not specified

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 16 mL/kg bw

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 18 000 mg/kg bw

Remarks on result:

other: No mortalities.

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:

LD50

Value:

16 000 mg/kg bw

Quality of whole database:

Animal studies are available for TEG, TTEG, and Crude Penta. These data consistently show very low acute oral LD50s at many times the limit dose. The database is sufficiently robust to draw conclusions regarding acute oral toxicity of the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: acceptable, well-documented publication which meets basic scientific principles

Justification for type of information:

Read across is based on the category approach. Please refer to attached category document.

Principles of method if other than guideline:

Followed the specific protocol and standard protocol amendment prepared by the Bushy Run Research Center.

GLP compliance:

yes (incl. QA statement)

Remarks:

testing lab.

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

The rats were assigned unique identification numbers by ear tags and were housed 5 per sex in stainless steel, wire-meah cages in 2 rooms for the prestudy quarantine and postexposure periods, respectively. The rats were kept on a 12-hour photoperiod throughout the entire study. Pelletal feed and tap water were available ad libitum except during exposure.
TEG was metered from a platon pump into an atomizer fitted with liquid nozzle and a No. 64 air nozzle.
The atomizer was positioned in the top of the inhalation chamber turret where the liquid aerosol was 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 set forth by the Toxic Substances Control Act (TSCA).
The concentration of TEG in the chamber was measured approximately every 30 minutes.
The nominal concentration was determined by dividing the weight of the test substance delivered by the volume of air which passed through the chamber during the exposure period.
The temperature and relative humidity in the animal housing room were recorded continuously with a 7-day recording hygrothermograph.
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 on post-exposure days 7 and 14.
A complete necropsy was performed for all animals.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: no data

Duration of exposure:

4 h

Concentrations:

5.2 mg/l

No. of animals per sex per dose:

5

Control animals:

no

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

Exp. duration:

4 h

Remarks on result:

other: No mortalities.

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) TEG concentration of 5.23 (±0.15) mg/l was obtained.

The nominal concentration was 19.3 mg/l.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The results of this study indicate that the LC50 value for TEG aerosol in rats is > 5.2 mg/l.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 200 mg/m³ air

Quality of whole database:

The database includes aerosol and saturated vapor LC50 studies conducted on TEG and substantially saturated vapor studies on TTEG and Crude Penta. The database is sufficiently robust to draw conclusions regarding acute inhalation toxicity of the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: basic information given

Justification for type of information:

Read across is based on the category approach. Please refer to attached category document.

Principles of method if other than guideline:

LD50 calculation

GLP compliance:

not specified

Test type:

standard acute method

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Type of coverage:

other: intact skin of the trunk

Vehicle:

not specified

Details on dermal exposure:

Animals weighing between 2.0 and 3.0 kg are subjected to 24 hours of contact with TEG which is retained under impervious sheeting on the clilpped, 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. 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.

Duration of exposure:

24 hours

Doses:

16.0 ml/kg

No. of animals per sex per dose:

5

Control animals:

not specified

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 16 mL/kg bw

Based on:

test mat.

Remarks on result:

other: 1 female animal died.

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

Remarks:

LD50 (18000 mg/kg) does not meet criteria for classification

Conclusions:

The LD50 for rabbits exposed to TEG dermally for 24 hours under occlusive conditions is >16 ml/kg (~ >18000 mg/kg).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

16 000 mg/kg bw

Quality of whole database:

The database includes LD50 studies conducted on TEG, TTEG, and Crude Penta and is sufficiently robust to draw conclusions regarding acute dermal toxicity of a formulation containing TEG and TTEG and similar to that of Crude Penta.

Additional information

Acute toxicity: via the oral route

Acute oral toxicity of TEG, TTEG, and Crude Penta (a mixture of higher ethylene glycols similar to the registered substance) has been assessed in rat studies.

In an acute oral toxicity weight of evidence study with TEG by Bushy Run Research Center (UCC, 1990), five male and five female Sprague-Dawley rats were exposed to 16 ml/kg TEG by intubation. No mortality was observed; the LD50 was >18000 mg/kg.

In a weight of evidence study by Bushy Run Research Center (UCC, 1986), no deaths were observed in five male and five female Sprague-Dawley rats exposed to 16 ml/kg TTEG by oral gavage; the LD50 was >18000 mg/kg.

In a supporting study of male rats exposed to TTEG, deaths occurred in 6/10, 5/6 and 3/4 at doses of 37500, 40000, and 50000 mg/kg, respectively (Mellon Institute for Union Carbide Corporation, 1940). The LD50 was reported as 30000 mg/kg. In another supporting study by the Mellon Institute for Union Carbide Corporation (UCC, 1938), an LD50 of 33000 mg/kg was found in male albino rats. An acute oral LD50 of > 3980 mg/kg for Polyol PS was found in a study by The Dow Chemical Company (1961), in which no deaths were observed, but very slight liver and kidney injury were noted at the high dose of 3980 mg/kg. In another study with TTEG by the Mellon Institute (UCC, 1972), an LD50 of 30.8 ml/kg (~34000 mg/kg) was found for male Wistar derived rats. A 1976 study by BASF determined the LD50 of TTEG to be >11240 mg/kg for male and female rats; no mortalities were observed.

In a weight of evidence study by Bushy Run Research Center (UCC, 1994), male and female Sprague Dawley rats received 16000 mg/kg Crude Penta by oral gavage. No mortality was observed; the LD50 of Crude Penta was >16000 mg/kg.

Animal studies assessing the acute oral toxicity of TEG, TTEG, and Crude Penta indicate very low acute oral toxicity, with LD50 values for each component or mixture occurring at many times the limit dose. These data suggest low acute oral toxicity for the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol.

Justification for selection of acute toxicity – oral endpoint
Of the weight of evidence studies for TEG, TTEG, and Crude Penta, each individual component and ethylene glycol mixture indicate very low acute oral toxicity.  The LD50 for the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol was based on that of Crude Penta due to its similarity to the registered substance.

Acute toxicity: via the inhalation route

Acute toxicity via the inhalation route was determined for TEG, TTEG, and Crude Penta (a mixture of higher ethylene glycols similar to the registered substance).

In a key study by Bushy Run Research Center (UCC, 1991), five male and five female Sprague-Dawley rats received whole body aerosol exposure to 5.2 mg/L TEG for 4 hours. No mortality occurred. In a supporting study by Bushy Run Research Center (UCC, 1990), five Sprague-Dawley rats/sex/dose were exposed to whole body TEG aerosol at concentrations of 2.6, 3.9, 5, and 6.7 mg/L for 4 hours. 100% mortality occurred in females exposed to 5 mg/L. No mortality occurred in a repeat exposure of five female rats to 5 mg/L or at the higher concentration of 6.7 mg/L. The 4 hr LC50 was considered greater than 3.9 mg/L. An additional supporting study by Bushy Run Research Center (UCC, 1986a) showed that no mortality occurred in male and female Sprague-Dawley rats exposed, whole body, to substantially saturated TEG vapor for 6 hours.

A supporting study by Bushy Run Research Center (UCC, 1986b) showed no mortality in male and female Sprague Dawley rats exposed for 6 hours to substantially saturated TTEG vapor. Similarly, Carnegie-Mellon University (UCC, 1972) showed no mortality in Wistar rats exposed to substantially saturated TTEG vapor for 8 hours. A supporting study by The Dow Chemical Company (1967) showed that acute inhalation exposure of rats for 2 hours to saturated TTEG vapors generated at 200ºC produced total mortality. However, no fatalities were observed when the duration of exposure was one hour. L(Ct)50 was estimated to be 671 mg.min./L. Although the authors described the exposure as essentially a saturated vapor atmosphere, the nominal concentration of 6.1 mg/L is substantially higher than that based on vapor pressure. Using a vapor pressure of 0.0000465 mm Hg at 25^oC corresponds to a saturated vapor concentration of 0.061 ppm (0.49 ug/L). Thus either the difference is mist (aerosol) or test material settled out of the airstream. Dow (1961) also described the results of a 7 hour inhalation of TTEG substantially saturated vapor generated at 110ºC. In this study, no mortality was observed, but some lung congestion and hemorrhage was observed after 1 to 3 days and slight liver and kidney injury were noted. The results of this supporting study suggest some slight upper respiratory and lung irritation from prolonged inhalation of test material heated to 110ºC. 

In a supporting study by Bushy Run Research Center (UCC, 1994), male and female Sprague Dawley rats were exposed to substantially saturated vapor of Crude Penta for 6 hours. No mortality was observed.

Based on these data, low inhalation toxicity is expected for the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol.

Justification for selection of acute toxicity – inhalation endpoint

An acute inhalation study on TEG provides an LC50 of >5.2 mg/L, a concentration exceeding the limit dose for acute inhalation toxicity studies. While aerosol inhalation studies are not available for TTEG or Crude Penta, acute toxicity of the registered substance is expected to adequately estimated with TEG is the smallest ethylene glycol component of the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol, allowing application of the TEG LC50 to conservatively predict acute inhalation toxicity of the reaction mass.

Acute toxicity: via the dermal route

Acute dermal toxicity has been determined for TEG, TTEG, and Crude Penta (a mixture of higher ethylene glycols similar to the registered substance).

In a key acute dermal toxicity study by Bushy Run Research Center (UCC, 1990), five New Zealand White rabbits/sex were dermally exposed to 16 mL/kg TEG under occlusion for 24 hours. The only death occurred in one female rabbit. The LD50 was >16 mL/kg (~18000 mg/kg).

In a supporting acute dermal toxicity study with TTEG by Carnegie-Mellon University (UCC, 1972), 24 hour occluded dermal exposure to the test material in male rabbits resulted in death of 2 rabbits at the high dose (20 mL/kg) and no deaths at the low dose (10 mL/kg). The LD50 for TTEG in this supporting study was 20 mL/kg (~22600 mg/kg). An additional supporting study by Bushy Run Research Center (UCC, 1986), found that 24 hour exposure of male and female New Zealand White rabbits to 16 mL/kg TTEG under occluded conditions resulted in no mortality.

In a supporting study by Bushy Run Research Center (UCC, 1994), male and female New Zealand White rabbits were exposed to 16000 mg/kg Crude Penta under occlusive conditions for 24 hours. No mortality was observed.

Based on these data, low dermal toxicity is expected for the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol.

Justification for selection of acute toxicity – dermal endpoint
In acute dermal toxicity studies of TEG and TTEG, components of the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol, and Crude Penta, a mixture containing similar components, LD50 values were many times the current limit dose of guideline studies. The LD50 of TEG was chosen to conservatively assign an LD50 value because TEG is the shortest ethylene glycol in the formulation and acute toxicity of ethylene glycols decreases with increasing number of EO repeats.

Justification for classification or non-classification

Acute toxicity: via the oral route

TEG and TTEG, components of the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol, demonstrate low acute toxicity after oral exposure in rats. A similar mixture, Crude Penta, also demonstrated low acute oral toxicity. Therefore, classification for the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol is not warranted.

Acute toxicity: via the inhalation route

No deaths were observed upon inhalation of substantially saturated vapor of individual TEG, TTEG, or Crude Penta. Moreover, no deaths were observed after a 4 hr whole body exposure to 5.2 mg/L TEG by male and female Sprague-Dawley rats. Therefore, the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol does not require classification under GHS.

Acute toxicity: via the dermal route

Low acute dermal toxicity has been demonstrated for TEG and TTEG, as well as for the Crude Penta mixture. The observed LD50 values were many times the current limit dose of guideline studies. Therefore, the reaction mass of 2,2'-(ethylenedioxy)diethanol and 3,6,9,12,15-pentaoxaheptadecane-1,17-diol and 3,6,9,12-tetraoxatetradecane-1,14-diol is not expected to be acutely toxic via the dermal route and should not be classified according to GHS.