2-hexyloxyethanol

Endpoint summary

Description of key information

Non-GLP studies equivalent to OECD guidelines 401, 402 and 403 are available in rats and rabbits. In addition, a GLP study equivalent to OECD guideline 403 is available.

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:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Report does not specify about GLP but equivalent to OECD guideline no 401 and sufficient data is available for the interpretation of study results.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

not applicable

GLP compliance:

no

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:

TEST ANIMALS
- Source: Not specified in the report
- Age at study initiation: Not specified in the report
- Weight at study initiation: 200-300 g
- Fasting period before study: Overnight
- Housing: Not specified in the report
- Diet ( ad libitum): Not specified in the report
- Water ( ad libitum): Not specified in the report
- Acclimation period: Not specified in the report


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not specified in the report
- Humidity (%): Not specified in the report
- Air changes (per hr): Not specified in the report
- Photoperiod (hrs dark / hrs light): Not specified in the report

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Sprague-Dawley albino 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 through 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. Five males and 5 females are included on each level used for the LD50 calculations.

Doses:

For male rats: 2.00 ml/kg, 1.41 ml/kg, 1.00 ml/kg and 0.50 ml/kg
For female rats: 4.0 ml/kg, 2.0 ml/kg, 1.0 ml/kg, 0.71 ml/kg, 0.50 ml/kg and 0.25 ml/kg

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights and gross pathology

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.

Preliminary study:

none

Sex:

male

Dose descriptor:

LD50

Effect level:

1.67 mL/kg bw

95% CL:

1.43 - 1.96

Remarks on result:

other: 1484 mg/kg

Sex:

female

Dose descriptor:

LD50

Effect level:

0.83 mL/kg bw

95% CL:

0.71 - 0.97

Remarks on result:

other: 738 mg/kg

Mortality:

For male rats: 2.00 ml/kg (5/5), 1.41 ml/kg (0/5), 1.00 ml/kg (5/0) and 0.50 ml/kg (0/3)
For female rats: 4.0 ml/kg (3/3), 2.0 ml/kg (3/3), 1.0 ml/kg (5/5), 0.71 ml/kg (0/0), 0.50 ml/kg (0/0) and 0.25 ml/kg (0/0)

Clinical signs:

other: Signs of toxicity included sluggishness, lacrimation, drooping eyelids, piloerection, labored breathing, red perinasal discharge (in 2) and prostration. Deaths occurred at 3 hours to 3 days. Survivors recovered at one to 3 days.

Gross pathology:

At necropsy, there were mottled and red lungs, red or liquid-filled stomachs, urinary bladders with red fluid and one liver nodule.

Other findings:

None

none

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Based on the results of this study acute oral LD50 for male and female rats receiving peroral doses of Hexyl CELLOSOLVE is 1.67 ml/kg (1484 mg/kg) and 0.83 ml/kg (738 mg/kgbw ) respectively.

Executive summary:

Ethylene glycol monohexyl ether was evaluated for acute oral test in rats. Sprague-Dawley albino rats, weighing between 200 and 300 g, received the Hexyl CELLOSOLVE (Ethylene glycol monohexyl ether) by stomach intubation with a ball-end stainless steel needle. The sample was injected through the needle by means of a syringe and doses are varied by adjusting the volume of the test material or its dilution. The rats were fasted overnight before dosing. Five males and 5 females are included on each level used for the LD50 calculations.

Signs of toxicity included sluggishness, lacrimation, drooping eyelids, piloerection, labored breathing, red perinasal discharge (in 2) and prostration. Deaths occurred at 3 hours to 3 days. Survivors recovered at one to 3 days. All survive animals gained body weights during 14 days of observation period. At necropsy, there were mottled and red lungs, red or liquid-filled stomachs, urinary bladders with red fluid and one liver nodule.

 

Based on the results of this study acute oral LD50 for male and female rats receiving peroral doses of Hexyl CELLOSOLVE is 1.67 ml/kg (1484 mg/kg) and 0.83 ml/kg (738 mg/kg bw) respectively.

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

738 mg/kg bw

Quality of whole database:

good

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:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was not conducted in accordance with GLP but sufficient data is available for the interpretation of study results.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

not applicable

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:

Not specified in the report

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Sealed 120 liter inhalation chamber
- Exposure chamber volume: 120 liter
- Source and rate of air: 2.5 lit/minute

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

6 h

Remarks on duration:

none

Concentrations:

Substantially saturated vapor, single exposure to rats: Static conditions at 26°C

No. of animals per sex per dose:

5/sex/exposure

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily observation and weekly body weights
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight and gross pathology

Statistics:

Means and standard deviations of animal body weights were calculated for descriptive purposes.

Preliminary study:

none

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 131.58 ppm

Exp. duration:

6 h

Remarks on result:

other: substantially saturated vapor concentration (calculated)

Mortality:

A single static inhalation exposure to substantially saturated vapor produced no deaths.

Clinical signs:

other: A single static inhalation exposure to substantially saturated vapor produced no signs of inhalation toxicity.

Body weight:

Body weight gains were observed in rats at 7 and 14 days post -exposure.

Gross pathology:

No gross pathologic lesions were found in any of the animals.

Other findings:

None

none

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

A single static inhalation exposure to substantially saturated vapor (equivalent to 131.58 ppm - calculated) produced no deaths or other signs of inhalation toxicity.

Executive summary:

Ethylene glycol mono hexyl ether was evaluated for acute inhalation test in rats. Sprague-Dawley albino rats, weighing between 200 and 300 g, were exposed to substantially saturated vapor for 6 hours. The vapor was produced by enclosing the test material in a sealed 120-liter animal chamber for approximately 18 hours (static conditions) or by passing air (at 2.5 liters/min) through the sample and then through a 9-liter animal chamber (dynamic conditions). Oxygen was added, as needed, for static exposures to maintain chamber oxygen content of approximately 20%. If deaths occur, exposure times are varied to determine an LT50. Five males and 5 females are included for each exposure period.

 

Exposure to a statically-generated, substantially saturated vapor produced no deaths of 5 male or 5 female rats during or following the 6-hour test. There were no signs of toxicity or remarkable gross pathologic lesions observed.

 

A single static inhalation exposure to substantially saturated vapor (equivalent to 131.58 ppm - calculated) produced no deaths or other signs of inhalation toxicity.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

good

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:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was not conducted in accordance with GLP but sufficient data is available for the interpretation of study results.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

not applicable

GLP compliance:

no

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:

Not specified in the report

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Clipped intact skin of the trunk
- Type of wrap if used: Vetrap bandaging tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

4 ml/kg, 2 ml/kg, 1 ml/kg and 0.5 ml/kg

No. of animals per sex per dose:

5/sex

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals observed daily and body weights taken weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight and gross pathology

Statistics:

Means and standard deviations of animal body weights were calculated for descriptive purposes.

Preliminary study:

none

Sex:

male

Dose descriptor:

LD50

Effect level:

0.81 mL/kg bw

95% CL:

0.59 - 1.12

Remarks on result:

other: calculated (757.35 mg/kg)

Sex:

female

Dose descriptor:

LD50

Effect level:

0.93 mL/kg bw

95% CL:

0.63 - 1.38

Remarks on result:

other: calculated (869.55 mg/kg)

Mortality:

Male: 4 ml/kg 5/5 , 2 ml/kg 5/5 , 1 ml/kg 4/5 and 0.5 ml/kg 0/5
Female: 4 ml/kg 5/5 , 2 ml/kg 5/5 , 1 ml/kg 3/5 and 0.5 ml/kg 0/5
Time to death ranged from one to 3 days. Survivors recovered at 2 to 4 days.

Clinical signs:

other: Local dermal effects included erythema, edema, ecchymosis, necrosis, desquamation, scabs and ulceration. A comatose appearance, red perinasal discharge, sluggishness and an unsteady gait were among the signs of toxicity observed.

Gross pathology:

Gross pathologic findings included mottled and pink to red lungs, red thymuses, a few red tracheas and dorsal alopecia.

Other findings:

None

none

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

By the percutaneous route, the LD50 for male rabbits was 0.81 ml/kg (calculated 757.35 mg/kg). The LD50 for females was 0.93 ml/kg (calculated 869.55 mg/kg)

Executive summary:

Ethylene glycol mono hexyl ether was evaluated for acute dermal test in rabbits. New Zealand White rabbits, weighing between 2.0 and 3.0 kg, were subjected to 24 hours of contact with the test material which was retained under impervious sheeting on the clipped, intact skin of the trunk. As necessary for larger doses, gauze was wrapped around the trunk over the sample to prevent leakage. Vetrap Bandaging Tape was wrapped over the impervious sheeting and the animal was returned to its cage for the contact period. Doses were varied by adjusting the volume or weight of the test material. Solids dosed as powders and were moistened with a sufficient amount of water or other suitable vehicle to form a paste. After the contact period, excess fluid was 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 were included on each level used for the LD50 calculation.

By the percutaneous route, the LD50 for male rabbits was 0.81 ml/kg. The D50 for females was 0.93 ml/kg. Local dermal effects included erythema, edema, ecchymosis, necrosis, desquamation, scabs and ulceration.

 

A comatose appearance, red perinasal discharge, sluggishness and an unsteady gait were among the signs of toxicity observed. Time to death ranged from one to 3 days. Survivors recovered at 2 to 4 days. Gross pathologic findings included mottled and pink to red lungs, red thymuses, a few red tracheas and dorsal alopecia.

 

By the percutaneous route, the LD50 for male rabbits was 0.81 ml/kg (calculated 757.35 mg/kg). The LD50 for females was 0.93 ml/kg (calculated 869.55 mg/kg)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

757 mg/kg bw

Quality of whole database:

good

Additional information

In the acute oral study, groups of male and female SD rats (5 rats/sex/dose) were exposed to different concentrations ranging from 0.25 ml/kg - 4.0 ml/kg of undiluted ethylene glycol hexyl ether and observed for 14 days, the study methodology followed was equivalent or similar to OECD TG 401. Based on the results of this study acute oral LD50 for male and female rats receiving peroral doses of ethylene glycol hexyl ether was 1.67 mg/kg

(1484 mg/kg) and 0.83 ml/kg (738 mg/kgbw ) respectively.

In this acute dermal study, groups of male and female New Zealand rabbits were exposed to varying concentrations ranging from 0.5 ml/kg to 4 ml/kg of undiluted ethylene glycol hexyl ether under occlusive conditions for 24 hours. By the percutaneous route, the LD50 for male rabbits was 0.81 ml/kg (calculated 757.35 mg/kg). The LD50 for females was 0.93 ml/kg (calculated 869.55 mg/kg)

Two acute inhalation toxicity studies in rats are available. In both studies no mortality was observed at saturated vapour concentrations after exposure to either a statically generated (6 hours) or a dynamically generated (4 hours) atmosphere of ethylene glycol hexyl ether. Rats exposed to either the dynamic or the static vapor from ethylene glycol hexyl ether exhibited no clinical signs of toxicity during exposure, or during the 14-day postexposure period. Body weight gains were observed at both 7 and 14 days postexposure for both exposure groups. In addition, no gross lesions were found at necropsy. Based on the results obtained in both studies, the LC0 for inhalation of ethylene glycol hexyl ether was greater than 131.58 ppm (787 mg/m3).

Justification for selection of acute toxicity – oral endpoint
reliable study

Justification for selection of acute toxicity – inhalation endpoint
reliable study

Justification for selection of acute toxicity – dermal endpoint
reliable study

Justification for classification or non-classification

Based on the oral and dermal LD50s, ethylene glycol hexyl ether should be classified for acute oral and dermal toxicity. As no mortality was observed after exposure to saturated vapour concentration, no classification for the acute inhalation route is proposed.

Based on the Oral LD50 value this substance meets the criteria for Oral Category 4 according to CLP.

Although this substance is corrosive (which should limit potential for dermal exposure), based on the dermal LD50 value this substance meets the criteria for Dermal Category 3 according to CLP. This is more severe classification than that currently reported in annex VI for this substance (Category 4 for dermal toxicity)