Registration Dossier

Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March-May 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study according to OECD guideline 404
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
n/a
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Identity: Dowanol-DPnB (n-butoxypropoxypropanol or
dipropylene glycol normal-butyl ether).
CAS # 29911-28-2
Batch No.: XZ 95411.00
Purity: More than 95%.
Appearance: Clear liquid.
Administered as: Undiluted liquid under semi-occlusive
dressing.
Vapor pressure: 0.06 mmHg at 25°C (79 ppm at 1 atm)
Specific Gravity: 0.91 kg/liter.
Solubility: 5% in water.
Storage: At ambient temperature in the dark.
Stability: Stable up to 200°C.

Dipropylene glycol n-butyl ether (DPnB) is a mixture of 4
possible isomers with the major isomers being
1-(1-n-butoxy-2-propoxy)-2-propanol and
2-(1-n-butoxy-2-propoxy)-1-propanol.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: The Broekman Institute, The Netherlands
- Age at study initiation: 9-10 weeks
- Weight at study initiation: n/a
- Housing: individually housed in cages with perforated floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 45-65
- Air changes (per hr): n/a
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To: n/a

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipping
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Concentration: 0.5 ml undiluted
Duration of treatment / exposure:
4 hour(s)
Observation period:
14 days
Number of animals:
3
Details on study design:
In a primary dermal irritation/corrosivity test, 0.5 milliliters of undiluted dipropylene glycol n-butyl ether (DPnB) was applied to a 6 x 6 cm square gauze patch, which was then applied to an area of clipped, unabraded skin on the left flank of three young adult female New Zealand white rabbits.  The test material was held in contact with the skin for a period of 4 hours under a semi-occlusive dressing.  After this period, the dressing and test material were removed by washing with tissues and water.  The site of application was evaluated for irritation by scoring 1) erythema/eschar and 2) edema.  Both criteria were scored on a scale of 0 - 4 at approximately 30 minutes after removal of the test material, and at 24, 48, and 72 hours, and on days 7 and 14.  The primary irritation index was calculated by averaging the combined scores for both criteria at 24 and 72 hours for all three animals.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
other: animal #1 mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
other: animal #2 mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
other: animal #3 mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
other: mean overall animals
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
other: animal #1 mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
other: animal#2 mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
other: animal#3 mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
other: mean overall animals
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Undiluted DPnB was found to have a primary irritation index of 2.0 (1.0 for erythema/eschar plus 1.0 for edema) averaged for the three animals at 24, 48 and 72 hours.  At 30 minutes and on days 1, 2, and 3, rabbits exhibited slight erythema and edema (scores of 1.0 for each).  Edema resolved in all subjects by day 7 and erythema by day 14.  All three subjects had slight scaliness over a portion of the treated site over the first 3 days, which disappeared by day 7.
Other effects:
none

Any other information on results incl. tables

none

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, dipropylene glycol butyl ether was calssified as not irritating to rabbit skin. Mean scores for erythema and edema were 1 for all animals.
Executive summary:

In a primary dermal irritation/corrosivity test, 0.5 milliliters of undiluted dipropylene glycol n-butyl ether (DPnB) was applied to a 6 x 6 cm square gauze patch, which was then applied to an area of clipped, unabraded skin on
the left flank of three young adult female New Zealand white rabbits.  The test material was held in contact with the
skin for a period of 4 hours under a semi-occlusive dressing.  After this period, the dressing and test material
were removed by washing with tissues and water.  The site of application was evaluated for irritation by scoring 1)
erythema/eschar and 2) edema.  Both criteria were scored on a scale of 0 - 4 at approximately 30 minutes after removal
of the test material, and at 24, 48, and 72 hours, and on days 7 and 14.  The primary irritation index was calculated
by averaging the combined scores for both criteria at 24 and 72 hours for all three animals.

Undiluted DPnB was found to have a primary irritation index of 2.0 (1.0 for erythema/eschar plus 1.0 for edema) averaged
for the three animals at 24 and 72 hours.  At 30 minutes and on days 1, 2, and 3, rabbits exhibited slight erythema and
edema (scores of 1.0 for each).  Edema resolved in all subjects by day 7 and erythema by day 14.  All three
subjects had slight scaliness over a portion of the treated site over the first 3 days, which disappeared by day 7.

No systemic toxicity was noted from topical application of DPnB for 4 hours.

This study was identified as key for this toxicity endpoint because of the methods followed (which were comprehensively
documented in the report).  The report included GLP and Quality Assurance statements, signed by the Study Director
and Head of the QA Unit, respectively.  The study report provided documentation that OECD Protocol 404: "Acute Dermal
Irritation/Corrosion"  was followed.  Specifically, the numbers and type of test animals used and their husbandry
conditions were as prescribed in the guidance.  Test material characterization was adequate. The amount of test
material applied complied with guidance, the length of the observation period (14 days) was sufficient, and scoring
criteria and averaging methods were typical for this type assay and adequately recorded.

The authors considered undiluted dipropylene glycol n-butyl ether to be slightly irritating. Classification: According to the criteria laid down in Annex VI of the EEC Council Directive 67/548/EEC (amended by Directive 83/467/EEC), the undiluted test substance would not require labeling as a skin irritant.