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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April-November 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study according to OECD guideline 405
Cross-reference
Reason / purpose:
reference to same 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 405 (Acute Eye 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.
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 / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Broekman institute
- Age at study initiation: 7-9 weeks
- Weight at study initiation: n/a
- Housing: individually housed in cages with perforated floor
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 13 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 45-80
- Air changes (per hr): n/a
- Photoperiod (hrs dark / hrs light): 12/12


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

Test system

Vehicle:
other: none
Controls:
not required
Amount / concentration applied:
Concentration: undiluted
Amount applied: 0.1 ml
Duration of treatment / exposure:
unrinsed
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3
Details on study design:
Undiluted DPnB (0.1 ml) was instilled into the conjunctival sac of the left eye of three female New Zealand white rabbits.  Lids were held together for a few seconds after instillation and the treatment solution was not washed out after 30 seconds.  Eyes were scored for irritation (compared to the negative control right eye) at various time intervals over a period of 23 days.  Readings were taken at 1 hour, 24 hours, 48 hours, 72 hours, 7 days, and 14 days after treatment.  In addition at 24 hours, eyes were treated with fluorescene dye to determine the severity and areal extent of any corneal involvement that might be present.  Eyes were evaluated for irritation based on 1) damage to the cornea (corneal opacity and area involved, both scored on a scale of 0 to 4) 2) damage to the iris (obvious physical damage and reaction to light, scored on a scale of 0 to 2), and 3) damage to conjunctivae (erythema [scale of 0 - 3] and chemosis [scale of 0 - 4]).  Overall scores were based on observations averaged from the 24, 48, and 72-hour observation intervals.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
other: animal#1 mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 0 days
Irritation parameter:
cornea opacity score
Basis:
other: animal#2 mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 0 days
Irritation parameter:
cornea opacity score
Basis:
other: animal#3 mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 0 days
Irritation parameter:
cornea opacity score
Basis:
other: mean over all animals
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 0 hour
Irritation parameter:
iris score
Basis:
other: animal #1 mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 0 hour
Irritation parameter:
iris score
Basis:
other: animal #2 mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 0 hour
Irritation parameter:
iris score
Basis:
other: animal #3 mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 0 hour
Irritation parameter:
iris score
Basis:
other: mean over all animals
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 0 hour
Irritation parameter:
conjunctivae score
Basis:
other: animal #1 mean
Time point:
other: 24, 48 and 72 hours
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae 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:
conjunctivae 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:
conjunctivae score
Basis:
other: mean over all animals
Time point:
other: 24, 48 and 72 hours
Score:
1.2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
other: animal #1 mean
Time point:
other: 24, 48 and 72 hours
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
other: animal #2 mean
Time point:
other: 24, 48 and 72 hours
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
other: animal #3 mean
Time point:
other: 24, 48 and 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
other: mean over all animals
Time point:
other: 24, 48 and 72 hours
Score:
0.6
Max. score:
1
Reversibility:
fully reversible within: 72 hours

Any other information on results incl. tables

Installation of 0.1 ml DPnB did not damage the cornea or iris.  The conjunctivae showed slight to moderate erythema
(redness) and chemosis (swelling) at 1, 24, 48, and 72 hours.  Swelling resolved by day 7 but slight redness
persisted through day 7, resolving by day 14.  Although corneal opacity scores were rated as 0, fluorescene dye
revealed some slight corneal damage (areal extent affected was 0, 20%, and 50% in the three subjects, respectively) at
24 hours.  The study authors reported a "Draize score" of 12.7 at 1 hour (presumably on a total scale of 110),
indicating slight irritation.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The lack of corneal and iridial involvement indicates slight eye irritation potential. Also, based on the estimated Draize score of 12.7 (1 hour) the test substance should be classified as mildly irritating according to the scheme of Kay and Calandra. According to the criteria laid down in Annex VI of the EEC Council Directive 67/548/EEC (amended by Directive 83/567/EEC), the test substance does not need to be labeled. Classification: not irritating
Executive summary:

Undiluted DPnB (0.1 ml) was installed into the conjunctival sac of the left eye of three female New Zealand white
rabbits.  Lids were held together for a few seconds after installation and the treatment solution was not washed out
after 30 seconds.  Eyes were scored for irritation (compared to the negative control right eye) at various time intervals
over a period of 23 days.  Readings were taken at 1 hour, 24 hours, 48 hours, 72 hours, 7 days, and 14 days after
treatment.  In addition at 24 hours, eyes were treated with fluorescene dye to determine the severity and areal extent
of any corneal involvement that might be present.  Eyes were evaluated for irritation based on 1) damage to the cornea
(corneal opacity and area involved, both scored on a scale of 0 to 4) 2) damage to the iris (obvious physical damage
and reaction to light, scored on a scale of 0 to 2), and 3) damage to conjunctivae (erythema [scale of 0 - 3] and
chemosis [scale of 0 - 4]).  Overall scores were based on observations averaged from the 24, 48, and 72-hour
observation intervals.

Installation of 0.1 ml DPnB did not damage the corneal or iris.  The conjunctivae showed slight to moderate erythema
(redness) and chemosis (swelling) at 1, 24, 48, and 72 hours.  Swelling resolved by day 7 but slight redness
persisted through day 7, resolving by day 14.  Although corneal opacity scores were rated as 0, fluorescene dye
revealed some slight corneal damage (areal extent affected was 0, 20%, and 50% in the three subjects, respectively) at
24 hours.  The study authors reported a "Draize score" of 12.7 at 1 hour (presumably on a total scale of 110),
indicating slight irritation.

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 405: "Acute Eye
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.

According to the criteria laid down in Annex VI of the EEC Council Directive 67/548/EEC (amended by Directive 83/567/EEC), the test substance does not need to be labeled.