Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1954
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given; similar to guideline study

Data source

Reference
Reference Type:
publication
Title:
Toxicology of mono-, di- and tri-propylene glycol methyl ethers
Author:
Rowe VK, McCollister DD, Spencer HC, Oyen F, Hollingsworth RL, and Drill VA
Year:
1954
Bibliographic source:
AMA Arch Ind Hyg Occup Med 9:509-525

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: see below
Principles of method if other than guideline:
Method used was essentially that of Draize JH, Woodard G and Calvery HO. (1944) Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J Pharmacol & Exper Therap. 82: 377-390.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
1-methoxypropan-2-ol is a close structural analogue of 1-ethoxypropan-2-ol, which is the major hydrolysis product of the submission substance (1-ethoxypropan-2-yl acetate).

- Name of test material (as cited in study report): Propylene glycol methyl ether
- Molecular formula (if other than submission substance):
- Molecular weight (if other than submission substance):
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type:
- Physical state:
- Analytical purity: essentially 100%
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date:
- Lot/batch No.:
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions:
- Storage condition of test material:
- Other:

Test animals

Species:
rabbit
Strain:
not specified
Sex:
not specified

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Type of wrap if used: impervious sleeves covered by heavy cloth bandages


REMOVAL OF TEST SUBSTANCE
- Washing (if done): cleansed with soap and water
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
5.0, 7.0 10.0, 12.0 or 15.0 ml/kg
No. of animals per sex per dose:
5 or 10 animals per group
Control animals:
no
Details on study design:
- Duration of observation period following administration: two weeks, or until it was certain that they had recovered from effects.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
approximate LD50
Effect level:
13.42 mL/kg bw
Based on:
test mat.
Mortality:
Deaths occurred within one to five days.
Clinical signs:
Within a few hours after dosing the animals exhibited symptoms of general narcosis varying in intensity from slight weakness and drowsiness to deep anesthesia. At the lower dosage levels, recovery from this narcotic effect was usually complete within 24 hours, but with the higher dosages recovery was prolonged, sometimes for several days.
Body weight:
All dosages caused some loss in body weight. Recovery from this response was rapid at doses of less than 10 ml per kg, but was usually prolonged for several days at the higher dosage levels.

Any other information on results incl. tables

For the purposes of risk assessment, a LOEL of 7ml/kg was defined by the submitter from this study (mild transient effects only). This is equivalent to

Applicant's summary and conclusion

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

Based on an early acute dermal toxicity study in rabbits, the single dose LD50 for methoxypropanol (a close structural analogue of the hydrolysis product of ethoxypropyl acetate) applied to the occluded skin for 24-hours is estimated to be 13.42 ml/kg (12.33g/kg) which is equivalent on a molar basis to 20.0g/kg. This data comes from an old study but the available information in the study publication suggest that the data can be considered a reliable indicator of the acute dermal toxicity of this substance.