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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:
10.11. - 11.11. 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
4-chlororesorcinol
EC Number:
202-462-0
EC Name:
4-chlororesorcinol
Cas Number:
95-88-5
Molecular formula:
C6H5ClO2
IUPAC Name:
4-chlorobenzene-1,3-diol
Test material form:
other:
Remarks:
beige powder
Details on test material:
Molecular weight: 144.65

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Age: at least 6 weeks
Body weight: between 1.0 and 3.5 kg
Conditions:
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 t 3.0°C (actual range: 19.2 - 21.8"C), a relative humidity of 30-70% (actual range: 37 - 67%) and 12 hours artificial
fluorescent light and 12 hours darkness per day.
Accommodation:
Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56~44~37c.m5 ). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet:
Standard laboratory rabbit diet, approx. 100 g/day.
Water:
Free access to tap-water.

Test system

Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
24 h
Observation period (in vivo):
1 h and 24 h
Number of animals or in vitro replicates:
1
Details on study design:
A health inspection was performed prior to commencement of treatrnent, to ensure that the animal was in a good state of health. Special attention was paid to the eyes, which were free from any abnormality.
On test day 1, 56.1 mg of the test substance (a volume of approximately 0.1 ml) was instilled in the conjunctival sac of an eye of one animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test
substance. The other eye remained untreated and served as the reference control.
lmmediately after the 24-hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the
total corneal area. Based on the severity of the ocular lesions observed during the study, the animal was sacrificed for ethical reasons immediately after the 24 hours observation and the two further rabbits assigned to the study were not treated.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 1 h
Score:
4
Max. score:
4
Remarks on result:
other: remnants of the test substance in the eye; brownish staining of the fur on head and paws by the test substance; grey/white discolouration of the eyelids and nictating membrane
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24 h
Score:
4
Max. score:
4
Remarks on result:
other: redness of the outside of the eyelids; remnants of the test substance in the eye; brownish staining of the fur on head and paws by the test substance; grey/white discolouration of the eyelids and nictating membrane
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 1 h
Remarks on result:
other: no scoring possible due to corneal irritation.
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24 h
Remarks on result:
other: no scoring possible due to corneal irritation.
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
other: 1 h
Score:
3
Max. score:
3
Remarks on result:
other: remnants of the test substance in the eye; brownish staining of the fur on head and paws by the test substance; grey/white discolouration of the eyelids and nictating membrane
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24 h
Score:
3
Max. score:
3
Remarks on result:
other: redness of the outside of the eyelids; remnants of the test substance in the eye; brownish staining of the fur on head and paws by the test substance; grey/white discolouration of the eyelids and nictating membrane
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 1 h
Score:
2
Max. score:
4
Remarks on result:
other: remnants of the test substance in the eye; brownish staining of the fur on head and paws by the test substance; grey/white discolouration of the eyelids and nictating membrane
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24 h
Score:
4
Max. score:
4
Remarks on result:
other: redness of the outside of the eyelids; remnants of the test substance in the eye; brownish staining of the fur on head and paws by the test substance; grey/white discolouration of the eyelids and nictating membrane
Irritation parameter:
other: Discharge
Basis:
animal #1
Time point:
other: 1 h
Score:
2
Max. score:
3
Remarks on result:
other: remnants of the test substance in the eye; brownish staining of the fur on head and paws by the test substance; grey/white discolouration of the eyelids and nictating membrane
Irritation parameter:
other: Discharge
Basis:
animal #1
Time point:
24 h
Score:
3
Max. score:
3
Remarks on result:
other: redness of the outside of the eyelids; remnants of the test substance in the eye; brownish staining of the fur on head and paws by the test substance; grey/white discolouration of the eyelids and nictating membrane
Irritant / corrosive response data:
Instillation of 56.1 mg of A 012 (a volume of approximately 0.1 ml) into an eye of one rabbit resulted in effects on the Cornea and conjunctivae. The corneal injury consisted of opacity (maximum .grade 4) and epithelial damage (100% of the corneal area). The irritation of the conjunctivae consisted of redness (also of the outside of the eyelids), chemosis and discharge. In addition, grey-white discolouration (a sign of necrosis) of the eyelids and nictitating membrane was noted during the observation period. Due to the corneal damage, iridial irritation could not be assessed. Based on the severity of the eye lesions, the ariimal was sacrificed for ethical reasons after the 24 hours observation. The other animals assigned to the study were not treated.
Other effects:
Colouration I Remnants
Remnants of the test substance were present in the eye at 1 and 24 hours after instillation. Brownish staining of the fur on the head and paws noted during the observation period was considered to have been caused by the animal's attempt to rub out test substance remnants andlor stained lachrymal fluid from the eye.

Toxicity/ Mortality
No symptoms of systemic toxicity were observed in the animal during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:
highly irritating
Conclusions:
Based on the degree and persistence of the eye lesions, it was concluded that ocular corrosion had occurred by instillation of A 012 into the rabbit eye.
Based on these results and according to the:
- OECD Harmonized lntegrated Hazard Classification System for Human Health and Environmental Effects of Chemical Substances (OECD, 1998),
A 012 should be classified as : having irreversible effects on the eyes (Class 1).
- EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), A 012 should be labelled as: risk of serious damage to eyes (R 41).
Executive summary:

Acute eye irritation/corrosion study with A 012 in the rabbit.

The study was carried out based on the guidelines described in: "Acute Toxicity - Eye irritation", OECD No.405 (2002), EC Commission Directive 92/69/EEC, 8.5, "Acute Eye Irritation/Corrosion" (1992) and US EPA, OPPTS 870.2400, Acute Eye Irritation, EPA 712-C-98- 195, August 1998 and JMAFF guidelines (2000).

A single sample of 56.1 mg of A 012 (a volume of approximately 0.1 ml) was instilled into an eye of one rabbit. Observations were made 1 and 24 hours after instillation.

Instillation of the test substance resulted in effects on the cornea and conjunctivae. The corneal injury consisted of opacity (maximum grade 4) and epithelial damage (100% of the corneal area). The irritation of the conjunctivae consisted of redness (also of the outside of the eyelids), chemosis and discharge. In addition, grey-white discolouration (a sign of necrosis) of the eyelids and nictitating membrane was noted during the observation period. Due to the corneal damage, iridial irritation could not be assessed.

Based on the severity of the eye lesions, the animal was sacrificed for ethical reasons after the 24 hours observation. The other animals assigned to the study were not treated.

Remnants of the test substance were present in the eye at 1 and 24 hours after instillation. Brownish staining of the fur on the head and paws noted during the observation period was considered to have been caused by the animal's attempt to rub out test substance remnants andlor stained lachrymal fluid from the eye. Based on the degree and persistence of the eye lesions, it was concluded that ocular corrosion had occurred by instillation of A 012 into the rabbit eye.

Based on the degree and persistence of the eye lesions, it was concluded that ocular corrosion had occurred by instillation of A 012 into the rabbit eye. Based on these results and according to the:

- OECD Harmonized lntegrated Hazard Classification System for Human Health and Environmental Effects of Chemical Substances (OECD, 1998), A 012 should be classified as: having irreversible effects on the eyes (Class 1).

- EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC),

A 012 should be labelled as: risk of serious damage to eyes (R 41).