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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:
04/1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-study according to OECD guideline

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)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Identity: Dowanol-PnB (1-butoxy-2-hydroxypropane or
propylene glycol normal-butyl ether). CAS # 29387-86-8 (also
5131-66-8).
Batch No.: redacted.
Purity: "More than 98%".
Supplied as: Not reported.
Appearance: Clear liquid.
Administered as: Diluted in water (emulsions).
Specific Gravity: 0.88 g/ml.
Solubility: 6% in water.
Storage: At ambient temperature in the dark.
Stability: Stable up to 200°C

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: The Broekman Institute, Someren, The Netherlands
- Age at study initiation: 7-9 weeks
- Weight at study initiation: 2975, 3212 and 3132 g
- Housing: individually housed in metal cages with perforated floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C
- Humidity (%): 45-80 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Concentration: 100 %
Amount applied: 0.1 ml
Duration of treatment / exposure:
single application
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM:
See other information on materials and methods

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: no effects observed
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: no effects observed
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
over all animals
Time point:
other: 24, 48 and 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: no effects observed
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
mean
Remarks:
over all animals
Time point:
other: 24, 48 and 72 hours
Score:
0.2
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
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:
animal #3
Remarks:
mean
Time point:
other: 24, 48 and 72 hours
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
over all animals
Time point:
other: 24, 48 and 72 hours
Score:
2.2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
over all animals
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
All three animals showed slight corneal opacity approximately 1 hour after exposure. In one rabbit this had already disappeared the next day, in the second animal on day 2 and in the third animal on day 7. On day 1, one animal showed slight swelling of the iridial blood vessels. One hour after exposure all three animals showed slight conjunctival redness and moderate chemosis. The next day the redness increased to obvious in two animals and to severe in one animal. Thereafter the redness decreased slowly and disappeared on day 7 in two animals and on day 14 in one animal. The chemosis decreased from moderate to slight on day 1, but was still visible on day 3 in all three rabbits. Treatment of the eyes with fluorescein 24 and 72 hours and 7 days after instillation of the test substance did reveal some epithelial damage. All three animals showed some lacrimation and an increased amount of discharge 1 hours after instillation. Two animals also showed some discharge on day 2 or 3.
Other effects:
No signs of systemic intoxication were observed.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the EU criteria for eye irritation PnB is classified as irritating to the eyes.
Executive summary:

Undiluted PnB (0.1 ml) was instilled into the conjunctival sac of the left eye of three female 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 read 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.  If necessary, evaluation
with fluorescene was repeated on days 3, 7, and 14.  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.  In this assay, the score after one hour was used to categorize the test material. Instillation of 0.1 ml PnB caused slight corneal opacity in all three subjects that cleared in one rabbit after one day,
the second rabbit in 2 days, and the third rabbit in 7 days (confirmed by evaluation with fluorescene dye).  Iridial
veins were swollen in two subjects, which cleared in one rabbit by 48 hours and in the second by 72 hours.  Chemosis
and erythema, sometimes severe, cleared by day 7 in all three rabbits.  Lacrimation and discharge were observed 1
hour after instillation, which continued in one subject until 4 days after treatment.