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Toxicological information

Acute Toxicity: dermal

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Administrative data

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.

Data source

Reference
Reference Type:
publication
Title:
The comparative acute toxicity and primary irritancy of the monohexyl ethers of ethylene and diethylene glycol.
Author:
Ballantyne B.; Myers R. C.
Year:
1987
Bibliographic source:
Vet Human Tox 29:361-366.

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
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

Test animals

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.

Administration / exposure

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.

Results and discussion

Preliminary study:
No data available
Effect levelsopen allclose all
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

Any other information on results incl. tables

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).

Applicant's summary and conclusion

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).