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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:
Unspecified to 1986-08-25
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study report without statement of guideline used for study or certification of following GLP; however, the methodology provided was equivalent to OECD 402.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Clinical observations were made before dose (0 days) and at 7 and 14 days instead of daily.
Principles of method if other than guideline:
N/A
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): DMEE (Dimethylaminoethoxyethanol)
- Molecular formula: (CH3)2NCH2CH2OCH2CH2OH
- Substance type: Pure active substance
- Physical state: liquid (amber, non-viscous)
- Analytical purity: 97.6
- Stability under test conditions: Stable for years as both undiluted test material and diluted in water.

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: between 2.0 and 3.0 kg

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Trunk
- % coverage: N/A
- Type of wrap if used: Vetrap Bandaging Tape wrapped over the impervious sheeting of the intact, clipped skin

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Excess fluid removed to diminish ingestion
- Time after start of exposure: 24 hrs
Duration of exposure:
24 hrs
Doses:
Males: 0.50, 1.00, 1.41, and 2.00 mL/kg (the last dose was inferred by reviewer from lower doses and LD50; first number is erased in study's table).
Females: 0.50, 1.00, 2.00 (this dose inferred by reviewer from other doses and LD50; first number is erased in study's table), and 4.00 mL/kg.
No. of animals per sex per dose:
5 males and 5 females were included on each level for the LD50 calculation.
Control animals:
yes, concurrent no treatment
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing at 0 days (before dose), 7 days and 14 days (just prior to sacrifice).
- Necropsy of survivors performed: yes
Statistics:
Moving average method (Thompson, 1947 (reference in OECD 402); Weil, 1983).

Results and discussion

Preliminary study:
N/A
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1.74 mL/kg bw
Based on:
test mat.
95% CL:
1.5 - 2.01
Remarks on result:
other: Using the density for DMEE of 0.95 g/mL to convert to mg/kg bw resulted in a LD50 value of 1663 mg/kg bw.
Sex:
female
Dose descriptor:
LD50
Effect level:
2.14 mL/kg bw
Based on:
test mat.
95% CL:
1.45 - 3.17
Remarks on result:
other: Using the density for DMEE of 0.95 g/mL to convert to mg/kg bw resulted in a LD50 value of 2033 mg/kg bw.
Mortality:
Time of death ranged from 1 to 4 days.
- Males: 4/5 of the 2.00 mL/kg group died, 0/5 of the 1.41 mL/kg group, 0/5 of the 1.00 mL/kg group, 0/5 of the 0.50 group.
- Females: 5/5 of the 4.00 mL/kg group, 2/5 of the 2.00 mL/kg group.
Clinical signs:
Local dermal effects included: erythema, edema, necrosis, ecchymosis, fissuring, ulceration, desquamation and scabs. Dermal reactions persisted through 14 days. Salvation, sluggishness, unsteady gait, red discharge (from nose and mouth), tremors (in 2) and prostration were among the signs of toxicity observed.
Recovery from the signs of toxicity:
Males: The survivor of the 2.00 mL/kg group recovered at 14 days; the 1.41 mL/kg group recovered in 2 to 14 days; and no signs of toxicity were noted in the groups exposed to 1.00 and 0.50 mL/kg.
Females: All of the 4.00 mL/kg group died; the 3 surviving animals from the 2.00 mL/kg group recovered at 2 to 14 days; the 1.00 mL/kg group recovered at 2 days; and no signs of toxicity were noted in the female group exposed to 0.50 mL/kg.
Body weight:
Weight gain was observed in all groups except for the 2.00 mL/kg male group, 1.41 mL/kg male group between 0-7 days, 2.00 mL/kg female group between 0-7 days, and 1.00 mL/kg female group between 0-7 days.
Gross pathology:
Gross pathology findings included red and mottled lungs, red tracheas, a few discolored livers and kidneys, and subcutaneous edema.
Other findings:
N/A

Any other information on results incl. tables

The author of the study concluded that DMEE was moderately toxic following its administration by single dermal application. The criteria used for interpretation of results is listed above under "Any other information on materials and methods incl. tables".

Applicant's summary and conclusion

Conclusions:
The LD50 for percutaneous exposure to male rabbits was 1.74 mL/kg (1663 mg/kg bw) and to female rabbits was 2.14 mL/kg (2033 mg/kg bw). Severe skin irritation was apparent on each rabbit through death or sacrifice at 14 days.