Lithium salt of branched-aliphatic dicarboxylic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-10-21 to 2014-11-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted under GLP conditions in accordance with the official OECD guideline No 405 (2012).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(2012)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(May, 2008)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

(August, 1998)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF, 12 Nousan, Notification No 8147 (November, 2000; including the most recent partial revisions)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Physical state: light yellow powder with lumps (determined at WIL Research Europe B.V.)
- Storage condition of test material: at room temperature in the dark
- Other: pH (1% in water, indicative range) 7.3-7.3 (determined by WIL Research Europe B.V.)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: between 12 and 24 weeks old
- Weight at study initiation: at least 1.5 kg
- Housing: individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
- Diet (e.g. ad libitum): Pelleted diet for rabbits approx. 100 grams per day; hay and wooden sticks ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before the start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): average 54.2 mg (range 54.0 - 54.4 mg)

Duration of treatment / exposure:

7 days

Observation period (in vivo):

Irritation: 1 hr, 24, 48, 72 hours and 7 days after instillation
Mortality/Viability: twice daily.
Toxicity: at least once daily.
Body Weight: day of treatment (prior to instillation) and after the final observation.

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: according to OECD 405 and in addition:

Area of cornea involved:
No ulceration or opacity: 0
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

Discharge:
No discharge (may include small amounts observed in inner canthus of normal animals): 0
Any amount different from normal and/or lacrimation: 1
Discharge with moistening of the lids and hairs just adjacent to lids: 2
Discharge with moistening of the lids and hairs (considerable area around the eye): 3


TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible

Results 3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible

Results 4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible

Results 5

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Results 6

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible

Irritant / corrosive response data:

Irritation: Instillation of approximately 54 mg of Lithium salt of branched-aliphatic dicarboxylic acid (a volume of approximately 0.1 mL) into one eye of each of three rabbits resulted in effects on the iris and conjunctivae.
Iridial irritation was observed 1 hour after installation and resolved within 24 hours.
The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 7 days in all animals.

No corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

Corrosion: There was no evidence of ocular corrosion.

Other effects:

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

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

Any other information on results incl. tables

Table1: Individual eye irritation scores

					Cornea				Iris		Conjunctivae				Comments
Animal	Time after dosing				Opacity (0-4)	Area (0-4)	Fluor area (%)^2		(0-2)		Redness (0-3)	Chemosis (0-4)	Discharge (0-3)
797^1	1 hour				0	0			1		2	2	2		-
	24 hours				0	0	0		0		2	1	1		-
	48 hours				0	0			0		1	1	1		-
	72 hours				0	0			0		1	0	0		-
	7 days				0	0			0		0	0	0		-
802	1 hour				0	0			1		2	2	2		-
	24 hours				0	0	0		0		2	1	1		-
	48 hours				0	0			0		1	0	1		-
	72 hours				0	0			0		1	0	1		-
	7 days				0	0			0		0	0	0		-
805	1 hour				0	0			1		2	2	2		-
	24 hours				0	0	0		0		2	1	1		-
	48 hours				0	0			0		1	1	1		-
	72 hours				0	0			0		1	1	1		-
	7 days				0	0			0		0	0	0		-

 

¹Sentinel,²  Green staining after fluorescein treatment (percentage of total corneal area)

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Iridial irritation was observed 1 hour after installation and resolved within 24 hours. The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 7 days in all animals. Based on these results, Lithium salt of branched-aliphatic dicarboxylic acid does not have to be classified for eye irritation.

Executive summary:

Acute eye irritation/corrosion study with Lithium salt of branched-aliphatic dicarboxylic acid in the rabbit.

 

The study was carried out based on the guidelines described in:

OECD No.405 (2012) "Acute Eye Irritation / Corrosion"

EC, No 440/2008, B5: "Acute Toxicity: Eye Irritation/Corrosion"

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

JMAFF Guidelines (2000), including the most recent revisions.

 

Single samples of approximately 54 mg of Lithium salt of branched-aliphatic dicarboxylic acid (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 days after instillation.

 

Instillation of the test substance resulted in effects on the iris and conjunctivae. Iridial irritation was observed 1 hour after installation and resolved within 24 hours. The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 7 days in all animals.

  

Based on these results, Lithium salt of branched-aliphatic dicarboxylic acid does not have to be classified and has no obligatory labelling requirement for eye irritation according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011)(including all amendments),

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).