Docosyltrimethylammonium methyl sulphate

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:

key study

Study period:

23.04.2008-24.04.2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 405; EU B.5). For justification for read-across see chapter 1 of the chemical safety report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

see below

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

see below

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

yes

Remarks:

see below

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF guidelines (2000) including the most recent partial revisions

Deviations:

yes

Remarks:

see below

Principles of method if other than guideline:

The body weight of the animal was not determined after sacrifice.
Evaluation: Sufficient data was available to assess the possible irritation or corrosion potential of the test substance.

The study integrity was not adversely affected by the deviations.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Quaternary ammonium compounds, C20-22-alkyltrimethyl, chlorides

EC Number:

271-756-9

EC Name:

Quaternary ammonium compounds, C20-22-alkyltrimethyl, chlorides

Cas Number:

68607-24-9

IUPAC Name:

68607-24-9

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan France SARL, Gannat, France
- Age at study initiation: 10-12 weeks old
- Weight at study initiation: 2215 g
- Housing: Individually in labeled cages with perforated floors (dimensions 56x44x37.5 cm).
- Diet (e.g. ad libitum): Pelleted diet for rabbits approximately 100 grams per day. Hay was provided at least three times a week
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: 5 days before start of treatment under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.3 ¿ 21.3
- Humidity (%): 45 - 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the other eye remained untreated and served as the reference control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 64.9 mg (volume of approx. 0.1ml)

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

1 and 24 hours after instillation of the test substance

Number of animals or in vitro replicates:

1 male

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done

SCORING SYSTEM: Draize scoring system

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #1

Time point:

other: 1 hour

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks:

within 24 hours

Results 2

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #1

Time point:

other: 24 hours

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks:

within 24 hours

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1 hour

Score:

1

Max. score:

2

Reversibility:

not reversible

Remarks:

within 24 hours

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24 hours

Score:

1

Max. score:

2

Reversibility:

not reversible

Remarks:

within 24 hours

Results 5

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: 1 hour

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks:

within 24 hours

Results 6

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: 24 hours

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks:

within 24 hours

Results 7

Irritation parameter:

conjunctivae score

Remarks:

chemosis

Basis:

animal #1

Time point:

other: 1 hour

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

within 24 hours

Results 8

Irritation parameter:

conjunctivae score

Remarks:

chemosis

Basis:

animal #1

Time point:

other: 24 hours

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

within 24 hours

Results 9

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

animal #1

Time point:

other: 1 hour

Score:

3

Reversibility:

not reversible

Remarks:

within 24 hours

Results 10

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

animal #1

Time point:

other: 24 hours

Score:

3

Reversibility:

not reversible

Remarks:

within 24 hours

Irritant / corrosive response data:

Instillation of approximately 65 mg of the test substance (a volume of approximately 0.1 mL) into an eye of one rabbit resulted in effects on the cornea, iris and conjunctivae.
The corneal injury consisted of opacity (maximum grade 2) and epithelial damage (100% of the corneal area). Iridial irritation grade 1 was observed and the irritation of the conjunctivae consisted of redness, chemosis and discharge.
Grey/white discoloration of the eyelids and nictating membrane (a sign of severe tissue damage) was noted. Erythema and oedema of the outside of the eyelids was noted.
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.

Other effects:

Remnants of the test substance were present in the eye on Day 1.
No staining of (peri) ocular tissues by the test substance was observed.
No symptoms of systemic toxicity were observed in the animal until the animal was sacrficed due to severe ocular effects.

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:

In a guideline-compliant acute eye irritation/corrosion study in rabbits, a supporting substance caused corneal opacity (maximum grade 2) with epithelial damage of 100% of the corneal area, iridial irritation grade 1, and irritation of the conjunctivae consisting of redness (grade 3), chemosis (grade 4) and discharge (grade 3) 24 hours after treatment. Signs of tissue damage of the eyelids and nictating membrane were observed as grey/white discoloration. Based on the severity of the ocular lesions observed during the study, the animal was sacrificed for ethical reasons after 24 hours. The supporting substance caused irreversible effects on the rabbit eye.

Executive summary:

An acute eye irritation/corrosion study with a supporting substance in the rabbit was carried out according to the following guidelines:

OECD No.405 (2002) "Acute Eye Irritation / Corrosion"

EC, Council Directive 67/548/EEC, An. V,B.5, (2004) "Acute Toxicity: Eye Irritation / Corrosion"

EPA, OPPTS 870.2400 (1998): "Acute Eye Irritation"

JMAFF guidelines (2000) including the most recent partial revisions.

 A single sample of approximately 65 mg of supporting substance (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, iris and conjunctivae.

The corneal injury consisted of opacity (maximum grade 2) and epithelial damage (100% of the corneal area). Iridial irritation grade 1 was observed and the irritation of the conjunctivae consisted of redness, chemosis and discharge. Grey/white discoloration of the eyelids and nictating membrane (a sign of severe tissue damage) was noted. Erythema and oedema of the outside of the eyelids was noted.  

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. 

Remnants of the test substance were present in the eye on Day 1.

Based on the degree of the ocular injury and observed necrosis, it was concluded that ocular corrosion had occurred by instillation of the supporting substance into the rabbit eye.