Registration Dossier

Administrative data

Description of key information

Several non-GLP studies in rabbits equivalent or similar to OECD guidelines 404 and 405 are available for dipropylene glycol methyl ether. These studies are supported by a human volunteer study for eye irritation and a 90-day dermal study in rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Method: BASF test
PROCEDURE
Before OECD Guideline 404 was established in 1982, skin irritation was tested using an internal method (BASF test).
White Vienna rabbits were used. Usually, 2 animals were treated for 5 minutes and for 2 hours using occlusive conditions. An application site of 2.5x2.5 cm was covered with the liquid or powdered and moistened test substance. In addition, skin tissue from the ear was tested by wrapping the ear. These results from the ear, however, would not be taken into account for evaluation as they do not represent testing of the dorsal / lateral flank of the back.

After the application time, the skin was washed with water which sometimes contained a mild detergent.

The animals were observed 5 days and skin changes were recorded on working days.

The report usually describes findings after 24 hours and at the end of the observation period. Thus, for final evaluation, the findings after 48 hours and 5 days from the raw data have to be taken into account.
The original BASF grading was converted into the numerical grading according to the OECD Draize system.
GLP compliance:
no
Species:
rabbit
Type of coverage:
occlusive
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): approx. 1 ml
- Concentration (if solution): undiluted
Duration of treatment / exposure:
Exposure times: 5 min and 2 hours
Observation period:
up to 5 days
Number of animals:
2 (1 male, 1 female)
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h, 48 h and 5 d
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 h, 48 h and 5 d
Score:
0
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Classification: not irritating
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study with human volunteers published in the peer reviewed literature. Sufficient data is available for interpretation of results in the publication.
Qualifier:
no guideline available
Guideline:
other: human volunteer study
GLP compliance:
not specified
Species:
human
Vehicle:
water
Controls:
no
Amount / concentration applied:
A droplet, 0.04 ml in volume, of 20% (v/v) aqueous DPGME was applied to the left eye using a micrometer syringe euipped with a soft polythene delivery tube.
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
Measurements were made a few minutes before applying DPGME to the eye, and at 2-4, 30 and 60 min after contaminating the eye.
Number of animals or in vitro replicates:
10 human male volunteers
Irritation parameter:
other: sensory irritation in human eyes
Basis:
other: data from 10 human volunteers
Time point:
other: 1 min to 2 hours after exposure
Score:
0
Reversibility:
fully reversible within: 2 hours
Remarks on result:
other: mild transient sensory irriation
Irritant / corrosive response data:
Application of a 0.04 ml of a 20% aqueous solution to human eyes produced  mild transient sensory irritation, hyperemia of conjunctival vessels and  a small increase in intraocular pressure.  All effects disappeared within  2 hr.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The test material was classified as not irritating to the eye based on this study with 10 human volunteers.
Executive summary:

10 informed male volunteers of age range 18 -26 yr, were used in the study in order to obtain effects of controlled applications of DPGME solutions to the human eye. A droplet, 0.04 ml in volume, of 20% (v/v) aqueous DPGME was applied to the left eye using a micrometer syringe equipped with a soft polythene delivery tube. Measurements were made a few minutes before applying DPGME to the eye, and at 2-4, 30 and 60 min after contaminating the eye. Application of a 0.04 ml of a 20% aqueous solution to human eyes produced  mild transient sensory irritation, hyperemia of conjunctival

 vessels and a small increase in intraocular pressure. All effects disappeared within 2 hr. The test material was classified as not irritating to the eye.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

All irritation studies available for dipropylene glycol methyl ether were conducted prior to GLP and OECD guidelines. However, the studies are well documented and are considered to be reliable. Several independent studies are available for each route of exposure reporting consistent results.

No irritation was observed in rabbits and humans in any study conducted with dipropylene glycol methyl ether.

Skin - There are two key studies available - BASF (1979) study in rabbits and Dow (1951) study in humans. In the rabbit study, the mean erythema and edema scores were 0 for all animals across 24, 48 hours and 5 days. In the human study no signs of irritation were noted in the 100 male and 100 female human subjects.

Eye - In the key study - Ballantyne (1984) study in humans, application of 0.04 ml of a 20% aqueous solution to eyes resulted in mild transient sensory irritation, hyperemia of conjunctival vessels and a small increase in intraocular pressure and all effects disappeared within 2 hours. In the supporting studies in rabbits, transient and mild irritation was observed and as such the mean corneal, iris, conjunctical and chemosis scores were lower than the prescribed cut off scores.

No respiratory irritation data is available for dipropylene glycol methyl ether. However, as no irritation has been observed after application to skin and eyes dipropylene glycol methyl ether is not expected to be a respiratory irritant.


Justification for selection of skin irritation / corrosion endpoint:
Acceptable, well-documented study report which meets basic scientific principles.

Justification for selection of eye irritation endpoint:
Study with human volunteers published in the peer reviewed literature. Sufficient data is available for interpretation of results in the publication.

Justification for classification or non-classification

Skin irritation: according to EEC Council Directive 67/548/EEC (amended by Directive 83/467/EEC) the mean value for erythema and edema scores was 0 for all animals at 24, 48 and 72 hours. According to annex VI of the directive dipropylene glycol methyl ether is not classified as skin irritant.

Eye irritation: according to the annex VI of the council directive 67/548 EEC (amended by directive 83/467 EEC) the average scores over all animals for

cornea opacity, iris lesions, conjunctivae and chemosis were 0.4, 0, 1.4 and 0.6, respectively at 24, 48 and 72 hours. According to EEC criteria no classification for eye irritancy is required.