Aromatic hydrocarbons, C10-13, reaction products with branched nonene, sulfonated, sodium salts

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 April - 15 May 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147, April 2011, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Aromatic hydrocarbons, C10-13, reaction products with branched nonene, sulfonated, sodium salts

EC Number:

800-660-7

Cas Number:

1258274-08-6

Molecular formula:

Not applicable, UVCB substance

IUPAC Name:

Aromatic hydrocarbons, C10-13, reaction products with branched nonene, sulfonated, sodium salts

Constituent 2

Reference substance name:

Sodium akylnaphthalene sulfonate (low nonene)

IUPAC Name:

Sodium akylnaphthalene sulfonate (low nonene)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Sodium akylnaphthalene sulfonate (low nonene)
- Substance type: Off-white powder
- Physical state: Powder
- Purity: 96.7 w/w%
- Lot/batch No.: 1156700
- Expiration date of the lot/batch: 20 February 2018
- Storage condition of test material: At room temperature in the dark under nitrogen
- pH: 7.9-7.8

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: Animals used within the study were 12 - 13 weeks old.
- Weight at study initiation: Body weights were between 2577 - 3172 kg.
- Housing: Individually housed in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 Harlan Teklad, Italy). Hay and wooden sticks were available during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.

IN-LIFE DATES: From: 02 April - 15 May 2014

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: One eye of each animal remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL- Amount(s) applied (volume or weight with unit): 92.6 mg (range 92.4 – 92.9 mg)

Duration of treatment / exposure:

Single instillation on Day 1.

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7, and 14 days after instillation of the test substance for one animal and 1, 24, 48 and 72 hours and 6, 7, 14 and 21 days after instillation for two animals.

Number of animals or in vitro replicates:

3 males

Details on study design:

PREEMPRIVE PAIN MANAGEMENT
Approximately one hour prior to instillation of the test substance, buprenorphine (Buprenodale®, Dechra Ltd., Stoke-on-Trent, United Kingdom) 0.01 mg/kg was administered by subcutaneous injection in order to provide a therapeutic level of systemic analgesia. Approximately five minutes prior to instillation of the test substance, two drops of the topical anesthetic lidocaïne eyedrops (AST Farma BV, Oudewater, The Netherlands) were applied to both eyes.

STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner three weeks later, after considering the degree of eye irritation observed in the first animal..

TREATMENT
Animals were treated by instillation of, on average, 92.6 mg (range 92.4 – 92.9 mg) of the test substance (a volume of approximately 0.1 mL), in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control. Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. This procedure was repeated to assess recovery. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area. Immediately after fluorescein examination on Day 2, in order to provide a continued level of systemic analgesia, buprenorphine 0.01 mg/kg and meloxicam (Metacam®, Boehringer Vetmed GmbH, Ingelheim/Rhein, Germany) 0.5 mg/kg were administered by subcutaneous injection.
Additional injections were supplied for all animals during the observation period to reduce pain and distress:
Time Description anaesthetic procedure
After 1 hr observation *1 sc 0.01 mg/kg buprenorphine
End of day *1 sc 0.01 mg/kg buprenorphine
After 24 hr obs end of the day *2 sc 0.03 mg/kg buprenorphine
After 48 hr observation *3 sc 0.01 mg/kg buprenorphine
After 48 hr observation *3 sc 0.5 mg/kg meloxicam

sc = subcutaneous injection.
*1 Due to score 3 for conjunctivae at 1-hr observation.
*2 Only for animal nos. 667 and 670.
*3 Due to score 3 for cornea and/or conjunctivae at 48 hr observation.

After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands).

REMOVAL OF TEST SUBSTANCE
-Washing: No

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to instillation) and after the final observation.
- Necropsy: No necropsy was performed according to protocol.
- Irritation:The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7, and 14 days after instillation of the test substance for one animal and 1, 24, 48 and 72 hours and 6, 7, 14 and 21 days after instillation for two animals. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 405.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

mean

Remarks:

(3 animals)

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: reversible in two animals, the third animal showed slightly dulling of the normal lustre of cornea

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

(3 animals)

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

(3 animals)

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 21 Days

Remarks on result:

other: Reversible in two animals and the third animal showed slightly erythema

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(3 animals)

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

Irritation and Corrosion: Instillation of approximately 93 mg of Sodium akylnaphthalene sulfonate (low nonene) (a volume of approximately 0.1 mL) into one eye of each of three rabbits resulted in effects on the cornea, iris and conjunctivae. The corneal injury consisted of opacity and epithelial damage. As a result of the corneal injury, pannus (neovascularization of the cornea) was apparent in all animals at 6 and/or 7 days after instillation for two animals, or between 6 and 21 days after instillation for one animal. The corneal injury resolved within 14 days in two animals, but slight dulling of the normal luster remained present up to the end of the observation period (21 days) in the other animal. Iridial irritation was observed in all animals and resolved within 6 or 7 days. The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 14 days in two animals, but redness remained present up to the end of the observation period (21 days) in the other animal. Reduced elasticity of the yelids was noted for one anima (no. 670) on Days 6 and 7. Gray-white discolouration of the nictating membrane (a sign of necrosis) was noted for one animal (no. 670) from 24 hours following instillation onwards.

Other effects:

Colouration/Remnants: No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen.

Toxicity/Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

Category I

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Sodium akylnaphthalene sulfonate (low nonene) showed irreversible effects in the eye of one of three rabbits tested, and should be GHS classified as having irreversible effects on the eyes (Category 1).

Executive summary:

Acute eye irritation/corrosion study with Sodium akylnaphthalene sulfonate (low nonene) in the rabbit. The study was carried out based on the guidelines described in OECD No.405 (2012) "Acute Eye Irritation / Corrosion".

 

Single samples of approximately 93 mg of Sodium akylnaphthalene sulfonate (low nonene) (a volume of approximately 0.1 mL) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours and 7, and 14 days after instillation for one animal and 1, 24, 48 and 72 hours and 6, 7, 14 and 21 days after instillation for two animals.

Instillation of the test substance resulted in effects on the cornea, iris and conjunctivae.

The corneal injury consisted of opacity and epithelial damage. As a result of the corneal injury, pannus (neovascularization of the cornea) was apparent in all animals at 6 and/or 7 days after instillation for two animals, or between 6 and 21 days after instillation for one animal. The corneal injury resolved within 14 days in two animals, but slight dulling of the normal luster remained present up to the end of the observation period (21 days) in the other animal. Iridial irritation was observed in all animals and resolved within 6 or 7 days. The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 14 days in two animals, but redness remained present up to the end of the observation period (21 days) in the other animal. Reduced elasticity of the eyelids was noted for one anima (no. 670) on Days 6 and 7. Gray-white discolouration of the nictating membrane (a sign of necrosis) was noted for one animal (no. 670) from 24 hours following instillation onwards.