2,2'-methylenebis(6-nonyl-p-cresol)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study pre-dates GLP and the standard guidelines; nevertheless, data is well summarised and the experiment is conducted in accordance with generally accepted scientific principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1973

Report date:

1973

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Test conducted in accordance with FHSA principles.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

6,6'-di-tert-butyl-4,4'-thiodi-m-cresol

EC Number:

202-525-2

EC Name:

6,6'-di-tert-butyl-4,4'-thiodi-m-cresol

Cas Number:

96-69-5

IUPAC Name:

4,4'-sulfanediylbis(2-tert-butyl-5-methylphenol)

Test material form:

solid: crystalline

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

100 mg applied as a finely ground powder.

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6

Details on study design:

SCORING SYSTEM: Draize Scale for Ocular Irritation.

Draize Scale for Scoring Ocular Irritation

1. CONJUNCTIVAE

(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal............................................................................................................................................0
Vessels definitely injected above normal................................................................................................1
More diffuse, deeper crimson red, individual vessels not easily discernible....................................2
Diffuse beefy red.........................................................................................................................................3

(B) Chemosis
No swelling..................................................................................................................................................0
Any swelling above normal (includes nictitating membrane).............................................................1
Obvious swelling with partial eversion of lids.......................................................................................2
Swelling with lids about half closed.........................................................................................................3
Swelling with lids half closed to completely closed...............................................................................4

(C) Discharge
No discharge...............................................................................................................................................0
Any amount different from normal (does not include small amounts observed in inner
canthus of normal animals)......................................................................................................................1
Discharge with moistening of the lids and hairs just adjacent to lids...............................................2
Discharge with moistening of the lids and hairs a considerable area around the eye...................3

THE TOTAL SCORE = (A + B + C) x 2 MAXIMUM TOTAL = 20

2. IRIS

(D) Values
Normal.........................................................................................................................................................0
Folds above normal, congestion, swelling, circumcorneal injection (any or all
of these or combination of any thereof) iris still reacting to light
(sluggish reaction is positive).................................................................................................................1
No reaction to light, haemorrhage, gross destruction (any or all of these)....................................2

THE TOTAL SCORE = D x 5 MAXIMUM TOTAL = 10

3. CORNEA

(E) Degree of Opacity (most dense area used)
No opacity...................................................................................................................................................0
Scattered or diffuse areas, details of iris clearly visible......................................................................1
Easily discernible translucent areas, details of iris slightly obscured..............................................2
Opalescent areas, no details of iris visible, size of pupil barely discernible....................................3
Opaque, iris not discernible through the opacity................................................................................4

(F) Area of Cornea Involved
One quarter (or less) but not zero..........................................................................................................1
Greater than one quarter but less than half...........................................................................................2
Greater than half but less than three quarters......................................................................................3
Greater than three quarters, up to whole area.......................................................................................4

THE TOTAL SCORE = (E x F) x 5 MAXIMUM TOTAL = 80

MAXIMUM TOTAL SCORE POSSIBLE = 110

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Remarks:

score for 6 rabbits

Time point:

other: Mean score for 24, 48 and 72 hours

Score:

5

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

- Immediately after administration: slight discomfort was seen.
- 10 minutes after administration: moderate erythema, very slight oedema and copious discharge were evident.
- 1 hour after administration: moderate to severe erythema, slight oedema and copious discharge.
- 24 hours: moderate to severe erythema, slight oedema and copious discharge containing slight whitish exudates.
- 48 hours: gradual improvement seen.
- 72 hours: all scored zero.

Any other information on results incl. tables

Table 1 Summary of Results

Time of Reading (hours)	Structure	Scores						Mean Score (Maximum possible 110)
		Animal Number
		1	2	3	4	5	6
24	-Cornea -Iris -Conjunctivae	0 0 14	0 0 14	0 0 16	0 0 12	0 0 12	0 0 14	13.6
48	-Cornea -Iris -Conjunctivae	0 0 2	0 0 0	0 0 6	0 0 0	0 0 0	0 0 2	1.6
72	-Cornea -Iris -Conjunctivae	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0.0
168	-Cornea -Iris -Conjunctivae	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0.0

 

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the test material is not classified for eye irritation in accordance with EU criteria.

Executive summary:

The potential of the test material to cause eye irritation was assessed in the New Zealand Albino rabbit.

100 mg of the test material was applied as a finely ground powder to the eyes of 6 test animals, with exposure lasting for 24 hours. The animals were observed for 7 days.

Moderate erythema and discharge were evident for the 24 hours following installation. However these effects were markedly improved by 48 hours and completely reversed after 72 based on these findings, no classification is required in accordance with EU criteria under the conditions of this study.