Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine

Eye irritation

Administrative data

Endpoint:

eye irritation, other

Remarks:

in vitro eye irritation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 January to 12 February 2013

Reliability:

1 (reliable without restriction)

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

TETA – Fatty acids adducts (Mw 600-1000Da)

IUPAC Name:

TETA – Fatty acids adducts (Mw 600-1000Da)

Constituent 2

Reference substance name:

High molecular weight adducts of Fatty acids, C18-unsatd dimers and trimers with amines, polyethylenepoly-, triethylenetetramine fraction

IUPAC Name:

High molecular weight adducts of Fatty acids, C18-unsatd dimers and trimers with amines, polyethylenepoly-, triethylenetetramine fraction

Constituent 3

Reference substance name:

lower molecular weight adducts of Fatty acids, C18-unsatd dimers with amines, polyethylenepoly-, triethylenetetramine fraction

IUPAC Name:

lower molecular weight adducts of Fatty acids, C18-unsatd dimers with amines, polyethylenepoly-, triethylenetetramine fraction

Constituent 4

Reference substance name:

Amines, polyethylenepoly-, tetraethylenepentamine fraction

EC Number:

292-587-7

EC Name:

Amines, polyethylenepoly-, tetraethylenepentamine fraction

Cas Number:

90640-66-7

IUPAC Name:

Amines, polyethylenepoly-, tetraethylenepentamine fraction

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): TOFA_DimerFA_TETA_PAA
- Physical state: Yellow liquid with a brown hue.
- Analytical purity: 100%
- Lot/batch No.: BB001030V1
- Expiration date of the lot/batch: 30 May 2013
- Storage condition of test material: When not in use the test article was stored in a sealed container, at room temperature in the dark.

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

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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.