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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
21 January to 12 February 2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to relevant test guidelines, with no deviations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
The test material, TOFA_DimerFA_TETA_PAA, was a pale yellow viscous material, with batch number BB 001030 V1 and a pH value of 7. The test material was stored in a sealed container at room temperature, in the dark. The analytical purity was 100%

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
The test animal was one male New Zealand White rabbit, obtained from Harlan UK Ltd., Bicester (HsdIf: NZW strain). The rabbit weighed 3.4 kg on Day -1, and was approximately 20 weeks old at administration. The animal was held in stock under laboratory conditions until the day before administration. A clinical examination and eye examination was performed prior to the study to ensure the animal was suitable for the test procedures. The rabbit was individually housed. Global Diet 2930C (Harlan Teklad, Bicester, UK) was provided ad libitum. Mains water was provided ad libitum via water bottles. Temperature was maintained at 15 to 21°C, humidity at 45%, and light was provided on a 12 hour cycle. There were 15 to 20 air changes per hour.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
Not applicable
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
1
Details on study design:
Both eyes of the rabbit were examined for indications of corneal, iridial or conjunctival damage or irritation on Day-1. After initial visual examination, one drop of 1% aqueous fluorescein solution was instilled into both lower conjunctival sacs, allowed to disperse for thirty seconds and removed from the eyes by irrigation with approximately 10 mL water for irrigation jetted gently from a syringe. The corneal surface was illuminated with an ultraviolet source and inspected for areas of absorption of the fluorescing dye that would indicate epithelial damage. Only rabbits with eyes free from damage or irritation were accepted onto study. One rabbit was dosed initially. The lower eyelid of the left eye was gently pulled aware from the eyeball, and of 0.1 mL test material was instilled into the conjunctival sac. After instillation the eyelids were held closed for a few seconds to prevent loss of the test material. The right eye remained untreated to serve as a control. The eyes were not washed for 24 hours after dosing. Serious ocular changes were observed in the first rabbit, therefore no further rabbits were dosed.
The rabbit was observed twice daily for general health and mortality. The rabbit was weighed on the day before administration, and following the last observation. Ocular reactions were recorded 30 minutes, 1 hour and 4 hours after treatment, and once on Day 2, 3 and 4 (at approximately 24, 48 and 72 hours post-treatment). Additional observations were performed twice daily up to Day 22 as necessary. Reactions were scored according to the Draize system. Fluorescein solution was used to assess corneal damage at the 24 hour observation. Body weight was recorded the day before dosing and following the last observation. The animal was sacrificed at the end of the observation period, necropsy was not performed.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
not reversible
Remarks:
within 21 days
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 hours
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 hours
Score:
2.67
Max. score:
2.67
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 hours
Score:
3.33
Max. score:
3.33
Reversibility:
not fully reversible within: 21 days
Irritant / corrosive response data:
Easily discernible translucent areas of corneal opacity were noted in the treated eye from 24 hours after instillation until Day 6. Scattered or diffuse areas of corneal opacity were noted from Day 7 to the end of the observation period. Iridial inflammation was noted from 30 minutes after instillation and persisted until the end of the observation period. Moderate conjunctival irritation was noted 30 minutes and 1 hour after instillation, with severe conjunctival irritation noted from 4 hours after instillation to Day 6. Moderate conjunctival irritation was noted on Day 7 and persisted until the end of the observation period.
Other effects:
No observations indicative of systemic toxicity or ill health were noted for any rabbits during the course of the study. On Day 7 a veterinary examination was carried out using a slip lamp on the left eye of the animal. The following findings were noted: iritis, scleritis, conjunctivitis, panus starting at edge of cornea and corneal oedema in ventral area, some fluorescein stain uptake dorsally (small spots) and more generally over area (ventrally) affected by oedema. There were no deep ulcerative lesions.

Any other information on results incl. tables

Table 1. Individual ocular response in one rabbit following administration of TOFA_DimerFA_TETA_PAA

Time after treatment

Individual ocular response – male rabbit

Cornea

Iris

Conjunctivae

Opacity

Area

Redness

Chemosis

Discharge

30 mins

0

0

1

2

3

2

1 hr

0

0

1

2

3

2

4 hrs

0

0

1

2

3

3

24 hrs*

2

4

1

2

3

3

48 hrs*

2

3

1

3

4

3

72 hrs*

2

2

1

3

3

3

Day 5*

2

2

1

3

2

3

Day 6*

2

2

1

3

2

3

Day 7*

1

2

1

2

1

3

Day 8*

1

2

1

2

1

2

Day 9*

1

1

1

2

1

2

Day 10*

1

1

1

2

2

3

Day 11*

1

1

1

2

2

3

Day 12*

1

1

1

1

1

3

Day 13*

1

1

1

1

1

3

Day 14*

1

1

1

1

1

3

Day 15*

1

1

1

1

1

3

Day 16*

1

1

1

1

1

3

Day 17*

1

1

1

1

1

3

Day 18*

1

1

1

1

1

3

Day 19*

1

1

1

1

1

2

Day 20*

1

1

1

1

1

2

Day 21*

1

1

1

1

1

2

Day 22*

1

1

1

1

1

2

* = fluorescein applied to cornea

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Effects on the cornea, iris and conjunctiva did not reverse within the 21 - day observation period therefore the test material was considered to be corrosive.
Executive summary:

The eye irritant potential of TOFA_DimerFA_TETA_PAA was evaluated in a single, male New Zealand White rabbit according to OECD 405. The undiluted test material (0.1 mL) was instilled into the left conjunctival sac of the rabbit on Day 1, the right eye remained untreated to serve as the control. Ocular reactions were assessed according to the Draize scoring system for 21 days after administration. Instillation of the test material produced easily discernible translucent areas of corneal opacity, iridial inflammation and severe conjunctival irritation. The effects on the cornea, iris and conjunctiva did not reverse within the 21 - day observation period therefore the test material was considered to be corrosive.

Based on the results of this study, the test material is classified as causing irreversible effects on the eye (Category 1) according to Regulation (EC) No 1272/2008.