RD 14156

Endpoint summary

Description of key information

The substnace is not a dermal irritant.

The substance is not an eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between 20 October 2015 and 18 January 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor Lot/Batch number 1004R17501


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature and humidity

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
- Preliminary purification step (if any):
- Final dilution of a dissolved solid, stock liquid or gel:
- Final preparation of a solid:

FORM AS APPLIED IN THE TEST (if different from that of starting material)

OTHER SPECIFICS:

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Covance Research Products Inc., Denver, PA, USA.
- Age at study initiation: ~27 weeks
- Weight at study initiation: 2.9 - 3.3 kg
- Housing: individually housed in suspended cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 20 October 2015 To: 23 October 2015

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g


VEHICLE
- Amount(s) applied (volume or weight with unit): 1.0

Duration of treatment / exposure:

72 h

Observation period:

72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: approx 6 sq cm
- % coverage: 100
- Type of wrap if used: non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): distilled water
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) 1, 24, 48 and 72 h

SCORING SYSTEM:
- Method of calculation: Draize technique

Irritation parameter:

erythema score

Basis:

animal: ALL

Time point:

24 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal: All

Time point:

24 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

erythema score

Basis:

animal: all

Time point:

48 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal: all

Time point:

48 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

erythema score

Basis:

animal: all

Time point:

72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal: all

Time point:

72 h

Score:

ca. 0

Max. score:

0

Results Table:

No. of animals	Dermal responses (time post exposure)	Erythema	Edema	Addiitonal dermal observations
Four-hour exposure
3	1 hr	Absent to very slight	Absent	NA
3	24 hr	Absent	Absent	NA
3	48 hr	Absent	Absent	NA
3	72 hr	Absent	Absent	NA
Systemic Observations		No abnormal physical signs were observed
Body weights		One animal gained bodyweight by study termination and two animals' weight remained the same
Conclusion		RC 14156 is not a dermal irritant

NA = Not Applicable

Interpretation of results:

GHS criteria not met

Conclusions:

RD 14156 is not a dermal irritant

Executive summary:

Objective:

To determine the irritant or corrosive effects, if any, of a test article when applied to the skin of a rabbit. This study was designed to comply with the standards set forth in the current OECD Guideline for Testing of Chemicals, Number 404 Acute Dermal Irritation/Corrosion.

Method Synopsis:

Since the test article was not expected to produce severe irritation or corrosion, three healthy New Zealand White rabbits (one male - two females) were dosed dermally with RD 14156. The test article (0.5 g) was applied dermally to one intact site per rabbit and wrapped with a semi-occlusive dressing. The test article was kept in contact with the skin for 4 hours at which time the wrappings were removed. Erythema and edema were scored at 1, 24, 48 and 72 hours. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction at these time periods. Animals were observed for mortality, toxicological and pharmacological effects at each dermal observation period. Body weights were recorded pretest and at termination.

Summary:

No. of animals	Dermal responses (time post exposure)	Erythema	Edema	Addiitonal dermal observations
Four-hour exposure
3	1 hr	Absent to very slight	Absent	NA
3	24 hr	Absent	Absent	NA
3	48 hr	Absent	Absent	NA
3	72 hr	Absent	Absent	NA
Systemic Observations		No abnormal physical signs were observed
Body weights		One animal gained bodyweight by study termination and two animals' weight remained the same
Conclusion		RC 14156 is not a dermal irritant

NA = Not Applicable

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between 20 October 2015 and 14 January 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor Lot/Batch number 1004R17501

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature and humidity


FORM AS APPLIED IN THE TEST (if different from that of starting material)

OTHER SPECIFICS:

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Covance Research Products, Inc., Denver, PA, USA
- Age at study initiation: ~27 weeks
- Weight at study initiation: 2.9 - 3.4 kg
- Housing: The animals were housed one per cage in suspended cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL equivalent to 32.5 mg RD 14156

Duration of treatment / exposure:

72 h

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done
- Time after start of exposure:

SCORING SYSTEM: OECD 405
The ocular irritation scores were evaluated in conjunction with the nature and severity of lesions, and their reversibility or lack of reversibility. The scores were categorized/classified as outlined below.

Non irritant: Substances that are not classified as EPA Category I, II, or III ocular irritants; or GHS eye irritation Category 1, 2, 2A or 2B; or EU Category 1 or 2.

Ocular irritant: A substance that produces a reversible change in the eye; Substances that are classified as EPA Category II or III ocular irritants; or GHS eye irritants Category 2, 2A or 2B; or EU Eye irritant Category 2.

Ocular corrosive: A substance that causes irreversible tissue damage to the eye; Substances that are classified as GHS eye irritants Category 1, or EPA Category I ocular irritants, or EU Category1.

Ocular severe irritant: A substance that causes tissue damage in the eye that does not resolve within 21 days of application or causes serious physical decay of vision; Substances that are classified as GHS eye irritant Category 1, or EPA Category I ocular irritants, or EU Category 1.

TOOL USED TO ASSESS SCORE: Mini-Maglite® flashlight equipped with a high intensity bulb/ fluorescein at 24h observation interval

Irritation parameter:

cornea opacity score

Basis:

animal: ALL

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal: ALL

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

48 h

Score:

1

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 1 hr

Score:

1

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 1 hr

Score:

1

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal: all

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

animal: all

Time point:

24 h

Score:

1

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal: all

Time point:

72 h

Score:

1

Max. score:

2

1. Ocular findings

Corneal opacity and iritis were not noted at any observation period. Conjunctival irritation, noted in three out of three eyes, cleared in two eyes by 24 hours, and in one eye by 72 hours. Additional ocular observations of test article residue in the conjunctival sac was noted at the 1-hour observation period. The control eyes appeared normal at all observation periods.

2. Systemic Observations and Body Weights

One animal was noted with few feces on Days 2 and 3. All other animals appeared normal. Two animals lost weight and one animal gained weight.

Interpretation of results:

GHS criteria not met

Conclusions:

Ocular irritant: A substance that produces a reversible change in the eye; Substances that are classified as EPA Category II or III ocular irritants; or GHS eye irritants Category 2, 2A or 28; or EU Eye irritant Category 2.

EU Classification Not classified
GHS Classification Not classified
US EPA Classification Category III

Executive summary:

Objective:

To determine the irritant or corrosive effects, if any, of a test article when instilled into the rabbit eye. This study was designed to comply with the standards set forth in the current EPA Health Effects Testing Guidelines, OCSPP Series 870.2400 and OECD Guidelines for Testing Chemicals, Number 405.

Method Synopsis:

Three healthy New Zealand White rabbits (two males - one female), free from evidence of ocular irritation and corneal abnormalities, were placed on the study. An analgesic, Buprenorphine was administered subcutaneously between the shoulder blades approximately 1 hour prior to instillation of the test article. A dose of 0.1 ml equivalent (32.5 mg) of RD 14156 was placed into the conjunctival sac of one eye of each rabbit. The eyes were examined pretest and scored by the Draize technique at 1, 24, 48 and 72 hours postdose. The control eyes were observed at the same time periods. Sodium fluorescein dye procedures were used at the 24-hour observation interval. Animals were evaluated for physical signs twice daily for the first three days of the study. Body weights were recorded immediately pretest and at termination.

Summary:

Corneal opacity and iritis were not noted at any observation period. Conjunctival irritation, noted in three out of three eyes, cleared in two eyes by 24 hours, and in one eye by 72 hours. Additional ocular observations of test article residue in the conjunctival sac was noted at the 1-hour observation period. The control eyes appeared normal at all observation periods. One animal was noted with few feces on Days 2 and 3. All other animals appeared normal. Two animals lost weight and one animal gained weight.

Conclusions:

OECD 405

Ocular irritant: A substance that produces a reversible change in the eye; Substances that are classified as EPA Category II or III ocular irritants; or GHS eye irritants Category 2, 2A or 2B; or EU Eye irritant Category 2.

EU Classification Not classified

GHS Classification Not classified

US EPA Classification Category III

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In a study to investigate skin irritation, very slight Erythema was observed in one rabbit at 1h time point, no erythema or edema effects seen in any other animlas at any time point.

In a study to investigate eye irritation, corneal opacity and iritis were not noted at any observation period, Although conjunctival irritation, was noted in three out of three eyes at the 1 -hour observation period, it cleared by 24 hours in all cases. Additional ocular observations of test article residue in the conjunctival sac were noted at the 1-hour observation period.

Justification for classification or non-classification

The substance has been tested and found not to be a skin irritant.

The substance has been tested and found not to be an eye irritant.

In accordance with the classifciation criteria described in CLP Regulation 1272/2008 the substance is not classified for skin irritation or eye irritation..