Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

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.

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:
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

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:
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.

Administration / exposure

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.

Results and discussion

Preliminary study:
No data available
Effect levelsopen allclose all
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

Any other information on results incl. tables

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).

Applicant's summary and conclusion

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).