dodecane-12-lactam, manufacturing of, by-products from, distillation residues

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 September 2011 - 13 November 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Compliant to GLP and testing guidelines; adequate consistence between data, comments and conclusions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

the relative humidity recorded in the animal room was sometimes outside of the target ranges specified in the study plan.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

idem above

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

dodecane-12-lactam, manufacturing of, by-products from, distillation residues

EC Number:

923-400-5

IUPAC Name:

dodecane-12-lactam, manufacturing of, by-products from, distillation residues

Test material form:

solid

Details on test material:

- Name of test material: Dodecane-12-Lactam Manufacturing of, by-products from, distillation residues
- Physical state: brown solid
- Lot/batch No.: AVRIL 2011
- Expiry date: 30 April 2012
- Composition of test material: UVCB
- Storage condition: at room temperature.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: breeder: Hypharm, La Corbière, Roussay, France
- Age at study initiation: at the beginning of the study, the animals were 2 to 4 months old
- Mean body weight at study initiation: a body weight of 3026 g and 3150 g, respectively
- Fasting period before study: no
- Housing: noryl cage
- Diet: free access to pelleted breeding diet "type 110C"
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h (7:00 - 19:00)

IN-LIFE DATES: 26 October 2011 to 13 November 2011.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated right eye served as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: A dosage-volume of 0.1 g/animal was used.

Duration of treatment / exposure:

Not applicable: single application not followed by rinsing.

Observation period (in vivo):

1, 24, 48 and 72 h; if relevant, daily until reversibility of reactions

Number of animals or in vitro replicates:

2 males.

Details on study design:

REMOVAL OF TEST SUBSTANCE: No

SCORING SYSTEM: Draize scale.

- Conjunctival chemosis (lids and/or nictitating membranes):
0 no swelling
1 any swelling above normal (includes nictitating membranes)
2 obvious swelling with partial eversion of lids
3 swelling with lids about half-closed
4 swelling with lids more than half-closed

- Conjunctival redness (palpebral and bulbar conjunctivae, cornea and iris):
0 blood vessels normal
1 a number of blood vessels definitely hyperemic (injected)
2 diffuse, crimson colour, individual vessels not easily discernible
3 diffuse, beefy red

- Discharge:
0 absence of discharge
1 slight discharge (does not include small amounts normally found in inner canthus)
2 discharge with moistening of lids and hairs adjacent to lids
3 discharge with moistening of lids and hairs on wide area around the eye

- Iris lesions
0 normal
1 markedly deepened rugae, congestion, swelling, moderate circum-corneal hyperemia,or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2 no reaction to light, haemorrhage, gross destruction (any or all of these)

- Cornea intensity of opacity (direct examination and, if necessary, with an UV lamp)
0 no ulceration or opacity
1 scattered or diffuse areas of opacity (other than slight dulling or normal lustre), details of iris clearly visible
2 easily discernible translucent area, details of iris slightly obscured
3 nacreous areas, no details of iris visible, size of pupil barely discernible
4 opaque cornea, iris not discernible through the opacity

- Cornea area of opacity (direct examination and, if necessary, with an UV lamp)
1 one quarter (or less) but not zero
2 greater than one quarter but less than a half
3 greater than one half but less than three quarters
4 greater than three quarters up to whole area

- Any other lesions observed were noted

TOOL USED TO ASSESS SCORE: UV lamp after instillation of 0.5% sodium fluorescein solution

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48 and 72 h (mean)

Score:

2.7

Max. score:

4

Results 2

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: 24, 48 and 72 h (mean)

Score:

3

Max. score:

3

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24, 48 and 72 h (mean)

Score:

1

Max. score:

1

Results 4

Irritation parameter:

cornea opacity score

Remarks:

(intensity)

Basis:

animal #1

Time point:

other: 24, 48 and 72 h (mean)

Score:

2

Max. score:

3

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h (mean)

Score:

3

Max. score:

3

Results 6

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

other: 24, 48 and 72 h (mean)

Score:

3

Max. score:

3

Results 7

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h (mean)

Score:

1

Max. score:

1

Results 8

Irritation parameter:

cornea opacity score

Remarks:

(intensity)

Basis:

animal #2

Time point:

other: 24, 48 and 72 h (mean)

Score:

2.3

Max. score:

3

Applicant's summary and conclusion

Interpretation of results:

Category 2A (irritating to eyes)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item was irritant when administered by the ocular route to rabbits.
According to the criteria of CLP Regulation, the test item should be classified category 2 and assigned the signal word "warning" and the hazard statement "H319: causes serious eye irritation".

Executive summary:

The objective of this study was to evaluate the potential irritant properties of the test item for the eye following a single administration to rabbits.

This study was conducted in compliance with the principles of Good Laboratory Practice according to guideline OECD 404.

The test item was first administered to a single male New Zealand White rabbit. As ocular reactions were oserved, a second animal was tested. The test item was administered in the conjunctival sac of the left eye. The right eye remained untreated and served as control. A quantity of 0.1 g/animal was used. Just after the 1-hour scoring, both eyes were rinsed with a sterile isotonic saline solution (0.9% NaCl). Each animal was observed once a day for mortality and clinical signs.Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until the reversibility of the ocular reactions. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal. Body weight was recorded on the day of treatment and the end of the observation period and sacrificed without macroscopic post-mortemexamination.

 

A chemosis (graded up to marked) was observed from day 1 to day 13 in the first animal and from day 1 to day 10 in the second animal.

A moderate to severe redness of the conjunctiva was observed in both animals, from day 1 to day 7 in the first animal and from day 1 to day 6 in the second animal. The redness was slight on day 8 in the first animal and on day7 in the second animal.

Iris lesions were noted from days 1 to 6 or or 5 in both animals. Corneal opacity was observed from days 2 to 5 in both animals. In addition, whitish purulent discharge was observed from days 2 to 6 in the first animal and from days 1 to 4 in the second animal.

Brownish area was observed on the conjunctiva from days 2 to 12 in the first animal and from days 6 to 11 in the second animal.

Mean scores calculated for each animal over 24, 48 and 72 hours were as follows:

.            chemosis: 2.7 and 3.0,

.            redness of the conjunctiva: 3.0 and 3.0,

.            iris lesions: 1.0 and 1.0,

.            corneal opacity: 2.0 and 2.3 for intensity; 1.7 and 1.7 for area

The test item was irritant when administered by the ocular route to rabbits.

According to the criteria of CLP Regulation,the test item should be classified category 2 and assigned the signal word "warning" and the hazard statement "H319: causes serious eye irritation".