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Administrative data

Description of key information

An acute oral toxicity test was performed in male and female rats leading to an oral LD50 of 4600 mg/kg bw for males and 3488 mg/kg bw for females (Ballantyne, 1987).
A dermal LD50 of 2001 mg/kg bw for male rabbits and 2216 mg/kg bw for female rabbits was found in an acute dermal toxicity test (Ballantyne, 1987).
An acute inhalation toxicity tests with saturated vapour atmosphere did not lead to any mortality in male and female rats (Ballantyne, 1987).

Key value for chemical safety assessment

Acute toxicity: via oral route

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Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Purity of the test material was not listed.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Hilltop-Wistar albino rats, weighing between 200 and 300 g, received the test material by stomach intubation to evaluate the acute oral toxicity of the test substance.
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): diethylene glycol monohexyl ether (DGHE)
- Physical state: Colorless liquid
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
The animals were maintained on appropriate commercial diet and municipal water. Both were available adlibitum except during periods of fasting.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Hilltop-Wistar albino rats, weighing between 200 and 300 g, received 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 were varied by adjusting the volume of the test material or its dilution.
The rats were fasted overnight before dosing. Five males and 5 females were included on each level.
Doses:
Males: 1, 2, 4, 8 or 16 mL/kg
Females: 2, 4, or 8 mL/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The animals were maintained on appropriate commercial diet and municipal water. Both were available adlibitum except during periods of fasting.
Dosage levels for the toxicity tests normally differ by a factor of 2 in a geometric series , but may differ by other constant factors if required . The maximum dosage for the peroral and percutaneous tests is 16 ml/kg. Dosages are reduced until significant signs of toxicity are not observed.
LD50's were calculated by the moving average method (Thompson, 1947) and were based on a 14-day observation period. Animal weights were 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. Hilltop-Wistar albino rats , weighing between 200 and 300 g, received 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 were varied by adjusting the volume of the test material or its dilution . The rats were fasted overnight before dosing. Five males and five females were included on each level.
Statistics:
Dosage levels for the toxicity tests normally differ by a factor of 2 in a geometric series , but might differ by other constant factors if required.
LD50's were calculated by the moving average method (Thompson, 1947) and were based on a 14-day observation period.
Preliminary study:
No data available
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
4.92 mL/kg bw
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
3.73 mL/kg bw
Mortality:
Mortality rates for males treated with 4, 8 or 16 mL/kg were 2/5, 4/5 and 5/5 and for females treated with 4 or 8 ml/kg were 3/5 and 5/5. All animals treated with 1 or 2 mL/kg survived. All deaths occurred within 1 day of dosing.
Clinical signs:
Sluggishness, unsteady gait and prostrate appearance were among the signs of toxicity observed.
Body weight:
Body weight gain was obsevred across the treatment groups.
Gross pathology:
Findings at necropsy included dark red or dark pink lungs, but only for animals that died during the study.
Other findings:
None

The LD50 values (with 95% confidence limits) were 4.92 mL/kg (3.09 -7.84) for males and 3.73 mL/kg (3488 mg/kg/bw) (2.52 - 5.52) for females. The slope of the dose-mortality curve was higher for females (4.96) than males (3.00).

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The LD50 values (with 95% confidence limits) were 4.92 mL/kg (3.09 -7.84) for males and 3.73 mL/kg (3488 mg/kg/bw) (2.52 - 5.52) for females.
Executive summary:

Fasted male and female rats (200 to 260 g) were divided into 5 groups of five animals each (males) and 3 groups of 5 animals each (females). Undiluted test material was administered by gavage to each group at the following concentrations: 1, 2, 4, 8 or 16 ml/kg (males) and 2, 4, or 8 ml/kg (females).  Animals were inspected twice daily for signs of toxicity for 14 days.  Body weights were taken before dosing, and 7 and 4 days after dosing.  Animals that died and all animals surviving the 14 day period were necropsied. LD50 values and their slopes were calculated by the moving average method. Mortality rates for males treated with 4, 8 or 16 ml/kg were 2/5, 4/5 and 5/5 and for females treated with 4 or 8 ml/kg were 3/5 and 5/5. All animals treated with 1 or 2 ml/kg survived. All deaths occurred within 1 day of dosing. Signs of toxicity included sluggishness, unsteady gait and prostrated appearance. Animals that died had red or dark pink lungs. All survivors gained weight over the 14 day period and had normal pathology. The LD50 values (with 95% confidence limits) were 4.92 ml/kg (3.09 -7.84) for males and 3.73 ml/kg (3488 mg/kg/bw) (2.52 - 5.52) for females. The slope of the dose-mortality curve was higher for females (4.96) than males (3.00).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
3 488 mg/kg bw

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Purity of the test material was not listed. Concentration of material in the atmosphere was not analyzed.
Principles of method if other than guideline:
Five rats of each sex weighing between 200 and 300g were exposed to a statically generated saturated vapour for 6 hours.
GLP compliance:
no
Test type:
fixed concentration procedure
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): diethylene glycol monohexyl ether (DGHE)
- Physical state: Colorless liquid
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
The animals were maintained on appropriate commercial diet and municipal water. Both were available adlibitum except during exposure period.
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
not specified
Details on inhalation exposure:
Five rats of each sex weighing between 200 and 300g were exposed to a statically generated saturated vapour for 6 hours. The vapour was produced by enclosing the test material into a sealed 120 liter animal chamber and allowing the vapour to equilibrate for 18 hours (Static condition). Rats were introduced into separate chambers through gasketted drawers designed to minimize vapour loss. Oxygen content was continuously monitored and maintained at 20%. Animals were removed from the chamber after 6 hours of exposure and were observed for 14 days. Body weights were measured before exposure and 7 and 14 days following exposure. All rats were subjected to necropsy after the 14 day observation period.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
6 h
Concentrations:
Substantially Saturated vapour (Static)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The animals were maintained on appropriate commercial diet and municipal water. Both were available adlibitum except during exposure period.
Five rats of each sex weighing between 200 and 300g were exposed to a statically generated saturated vapour for 6 hours. The vapour was produced by enclosing the test material into a sealed 120 liter animal chamber and allowing the vapour to equilibrate for 18 hours (Static condition). Rats were introduced into separate chambers through gasketted drawers designed to minimize vapour loss. Oxygen content was continuously monitored and maintained at 20%. Animals were removed from the chamber after 6 hours of exposure and were observed for 14 days. Body weights were measured before exposure and 7 and 14 days following exposure. All rats were subjected to necropsy after the 14 day observation period.
Statistics:
Not applied
Preliminary study:
No data available
Key result
Sex:
male/female
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: Substantial Saturated Vapours-Concentration Unknown
Remarks:
No mortality occurred
Mortality:
None. All animals survived the 6 hour exposure.
Clinical signs:
There were no signs of toxicity or irritancy during or after exposure.
Body weight:
Body weight gain was observed across the treatment groups.
Gross pathology:
None
Other findings:
None
Interpretation of results:
study cannot be used for classification
Conclusions:
No signs of inhalation toxicity were observed when rats were exposed to substantially saturated vapours for 6 hours.
Executive summary:

Five rats of each sex weighing between 200 and 300g were exposed to a statically generated saturated vapour for 6 hours. The vapour was produced by enclosing the test material into a sealed 120 liter animal chamber and allowing the vapour to equilibrate for 18 hours (Static condition). Rats were introduced into separate chambers through gasketted drawers designed to minimize vapour loss. Oxygen content was continuously monitored and maintained at 20%. Animals were removed from the chamber after 6 hours of exposure and were observed for 14 days. Body weights were measured before exposure and 7 and 14 days following exposure. All rats were subjected to necropsy after the 14 day observation period. All animals survived the 6 hour exposure. There were no signs of toxicity or irritancy during or after exposure. Animals gained weight over the fourteen day observation period and had normal pathology.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

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Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Purity of the test material was not listed.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Undiluted test material was applied to the clipped trunk skin of groups of 5 male or female rabbits (2 to 3 kg) at the following concentrations: 1, 2 or 4 mL/kg (males), and 1, 2, 2.8 or 4 mL/kg (females).  Animals were examined twice daily for 14 days for signs of local irritation and systemic toxicity.  Body weights were taken before dosing and 7 and 14 days following dosing. Necropsies were performed on animals that died and all animals surviving the 14 day observation period.  
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): diethylene glycol monohexyl ether (DGHE)
- Physical state: Colorless liquid
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
The animals were maintained on appropriate commercial diet and municipal water. Both were available ad libitum except during periods of manipulation or restraint.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
New Zealand White rabbits, weighing between 2.0 and 3.0 kg, were immobilized during a 24-hr contact period. The test material was retained under impervious sheeting on the clipped, intact skin of the trunk. After the contact period, residual material was gently removed from the skin with moist tissue.
Duration of exposure:
24 hours
Doses:
Males: 1, 2 or 4 mL/kg
Females: 1, 2, 2.8 or 4 mL/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The animals were maintained on appropriate commercial diet and municipal water. Both were available adlibitum except during periods of manipulation or restraint. New Zealand White rabbits, weighing between 2.0 and 3.0 kg, were immobilized during a 24-hr contact period. The test material was retained under impervious sheeting on the clipped, intact skin of the trunk.After the contact period, residual material was gently removed from the skin with moist tissue. Observations for skin reaction were made at one hour, 7 days and 14 days after the contact period. Five males and five females were included on each level.
Statistics:
LD50's were calculated by the moving average method (Thompson, 1947) and were based on a 14-day observation period.
Preliminary study:
No data available
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
2.14 mL/kg bw
95% CL:
1.45 - 3.17
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
2.37 mL/kg bw
95% CL:
2.03 - 2.76
Mortality:
All animals treated with 2.8 or 4.0 mL/kg died within 6 days of exposure.Two out of five male rats dosed with 2.0 mL/kg died within 2 days.  None of the females treated with 2.0 mL/kg died.  
There were no deaths in males or females treated with 1 mL/kg.
Clinical signs:
Erythema, edema, necrosis, desquamation, fissuring and scabs were observed on the dose sites.
Signs of toxicity included salivation, sluggishness, unsteady gait and comatose appearance. These signs occurred during exposure and survivors recovered within 3 to 4 days.
Body weight:
Body weight gain was observed at the end of the observation period (14 days). Although, there was body weight loss at 7 days at 2 mL/kg, female group.
Gross pathology:
Gross pathological examination of animals that died revealed dark red or dark pink lungs, which were also seen in a few of the survivors (doses, sex and number not stated).
Other findings:
None

The LD50 values (with 95% confidence limits) were 2.14 ml/kg (1.45 - 3.17) for males and 2.37 ml/kg (2.03 - 2.76) ml/kg for females.  The slope of the dose-mortality curve was steeper for females (13.3) than males (4.96).

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The LD50 values (with 95% confidence limits) were 2.14 mL/kg (1.45 - 3.17) for males and 2.37 ml/kg (2.03 - 2.76) mL/kg for females.
Executive summary:

Undiluted test material was applied to the clipped trunk skin of groups of 5 male or female rabbits (2 to 3 kg) at the following concentrations: 1, 2 or 4 ml/kg (males), and 1, 2, 2.8 or 4 ml/kg (females). An occlusive dressing consisting of polyethylene sheeting, adhesive tape and plastic ties was used to keep the material in contact with the skin.  Animals were immobilized during the 24 hour contact period. Test material was then removed with moist tissue.  Animals were examined twice daily for 14 days for signs of local irritation and systemic toxicity.  Body weights were taken before dosing and 7 and 14 days following dosing. Necropsies were performed on animals that died and all animals surviving the 14 day observation period.  LD50 values and their slopes werecalculated by the moving average method. All animals treated with 2.8 or 4.0 ml/kg died within 6 days of exposure.Two out of five male rats dosed with 2.0 ml/kg died within 2 days.  None of the females treated with 2.0 ml/kg died. There were no deaths in males or females treated with 1 ml/kg. Animals that died had dark red or pink lungs. These effects were also noted in some of the animals that survived (doses, sex and number not stated). Signs of toxicity included salivation, sluggishness, unsteady gait and comatose appearance. These signs occurred during exposure and survivors recovered within 3 to 4 days. Females treated with 2.0 ml/kg lost weight over the first week of recovery but then recovered. Erythema, edema, necrosis and ecchymoses were found at the application site up to study termination (doses not stated). The LD50 values (with 95% confidence limits) were 2.14 ml/kg (1.45 - 3.17) for males and 2.37 ml/kg (2.03 - 2.76) ml/kg for females. The slope of the dose-mortality curve was steeper for females (13.3) than males (4.96).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
2 001 mg/kg bw

Additional information

An acute oral toxicity test was performed following an OECD 401-type protocol with 5 rats per dose and sex. The oral LD50found for male rats was 4600 mg/kg bw, and 3488 mg/kg bw for female rats.

An acute dermal toxicity test with rabbits (5 per dose and sex, OECD 402-type) treated with a 24-h occlusive patch reveiled a dermal LD50of 2001 mg/kg bw for male and 2216 mg/kg bw for female rabbits.

An acute inhalation toxicity test did not lead to any mortality in male and female rats exposed to a saturated vapour atmosphere for 6 h.

Justification for classification or non-classification

Based on the results of the acute oral toxicity study with rats, the test substance is not classified for acute oral toxicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. According to UN GHS the substance has to be regarded as Acute Tox 5, H303: May be harmful if swallowed.

The substance proved not toxic via inhalation at saturated vapour atmosphere (classification not possible without data on actual vapour concentration).

The test substance is classified as Acute Tox 4, H312: Harmful in contact with skin according to Annex VI of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.