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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:
1944
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This is a very old study that does not meet the full requirements of current OECD guidelines (not all end points reported). Nevertheless, it is reported in some detail and the method followed forms the basis for current testing methods and provides the key required parameter of a trustworthy LD50. It is therefore considered a reliable contribution to understanding the acute dermal toxicity of this substance.
Cross-reference
Reason / purpose:
reference to other study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes
Author:
Draize JH, Woodward G, Calvery HO
Year:
1944
Bibliographic source:
J Pharmac exp Ther, 82, 377
Reference Type:
publication
Title:
Toxicological investigations of compounds proposed for use as insect repellants
Author:
Draize JH, Alvarez, E, Whitesell MF, Woodward, G, Hagan EC, Nelson AA
Year:
1948
Bibliographic source:
J Pharmac Exper Ther, 43, 26

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
See below
Principles of method if other than guideline:
Study pre-dates guidelines but follows the basic principles of current methods
GLP compliance:
no
Remarks:
pre-dates guidelines
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
No data on purity. Referred to as diethylene glycol monobutyl ether acetate

Test animals

Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.5-3.5kg
- Housing: no data during study but metabolism cages used to collect urine during observation period.
No further data

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: trunk
- % coverage: 10.7%
- Type of wrap if used: rubber sleeve made from rubber dam

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): sufficient to furnish a reservoir for the dose

OTHER
- Preparation of test site: clipping 24 hours prior to exposure. Half animals also subjected to epidermal abrasions 2 cm apart
Duration of exposure:
24 hours
Doses:
Not specified for main test but preliminary range finder doses 3.9, 6.0 and 9.4ml/kg
No. of animals per sex per dose:
Study states 'sufficient to calculate the fatal dose', but no specific numbers given. Total number of animals used in study 100.
Control animals:
other: concurrent testing of other substances effectively provided controls
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes, but only on animals that died before end of observation period
- Other examinations performed: clinical signs, body weight, food consumption, organ weights, urine, blood morphology
Statistics:
Method of Bliss (Quart. J. Pharm Pharmacol, 11, 192, 1938)

Results and discussion

Effect levelsopen allclose all
Sex:
not specified
Dose descriptor:
LD50
Effect level:
5.75 mL/kg bw
Remarks on result:
other: Results quoted in 1944 reference
Sex:
not specified
Dose descriptor:
LD50
Effect level:
5.5 mL/kg bw
Remarks on result:
other: Result quoted in 1948 reference
Mortality:
No data
Clinical signs:
No data
Body weight:
No data
Gross pathology:
No data
Other findings:
No data

Any other information on results incl. tables

The 1948 reference is a compilation of results from this author's previous work. It is believed to be the quote the same results as from the 1944 reference, even though the quoted figures differ slightly.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

In an old acute dermal toxicity study, 2 -(2 -butoxyethoxy)ethyl acetate was found to have an LD50 of around 5.5 -5.8ml/kg in rabbits. This study did not meet the full requirements of current OECD guideline (not all end points reported), but the method was reported in some detail and the results therefore considered reliable.

Synopsis

LD50 = 5.5 -5.8ml/kg (equivalent to 5400 - 5700mg/kg)