Registration Dossier

Skin Irritation: Not a dermal irritant

Ocular Irritation: Not an ocular irritant

Reference

Endpoint:

skin irritation: in vivo

Remarks:

In vivo study

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-08-11 to 2011-03-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Principles of method if other than guideline:

Deviations of temperature and humidity (for several days during the study) were deemed to have had no adverse effects on the study animals or the integrity of the study, since all the animals gained weight normally, and were free from signs of stress based on daily observations.

GLP compliance:

yes

Specific details on test material used for the study:

Label Identity: Santicizer P-1400
Batch No: RP-620
Supplied by: Ferro Corporation
Data received: 08/19/2010
Storage: Room temperature and humidity
Description: Clear yellow liquid
Sample preparation: Te test article was used as received

Species:

rabbit

Strain:

New Zealand White

Remarks:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Myrtle Rabbitry Inc., Thompson Station, TN
- Received on: 10/21/10
- Date of birth: 07/20/10
{Age at study initiation 3 months 21 days - study initiation date mm/dd 11/09/2010}
- Weight at study initiation: 2.7 -3.0 kg
- Housing: suspended wire bottom cages
- Diet (e.g. ad libitum): Fresh PMI Rabbit Chow (Diet #5321) - daily
- Water (e.g. ad libitum): freeily available
- Acclimation period: (>5 days) - approx 3 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C):[ Room temperature]. Parameters deviated from the protocol for several days during the study;
- Humidity (%): Parameters deviated from the protocol for several days during the study - Deviations of temperature and humidity were deemed to have had no adverse effects on the study animals or the integrity of the study, since all the animals gained weight normally, and were free from signs of stress based on daily observations.
- Air changes (per hr): no info
- Photoperiod: 12 hr light/12 hr dark
Fresh PMI rabbit chow was priovided daily (diet #5321) and drinking water was available ad-lib. The animal room was kept clean and vermin-free.
IN-LIFE DATES:
Study initiation: 11/08/2010
Experimental start due: 11/09/2010
Experimental term data: 11/12/2010
Draft report signed: 01/07/2011
Final report signed: 03/03/2011

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml/site applied to a 2x3 cm gauze patch.

Duration of treatment / exposure:

4 hours

Observation period:

60 minutes, 24, 48, 72 hours post patch removal

Number of animals:

3 male rabbits

Details on study design:

TEST SITE
- Area of exposure: 10x10
- % coverage: 3x3 cm
- Type of wrap if used: porous, not irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): ethanol (end of exposure time) prior scoring

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

Dermal observations:
Well defined erythema and very slight edema was observed at 1 hour following the 4 hour exposure. At 24 and 48 hours, absent to very slight erythema and very slight edema was observed. No erythema or edema was observed at 72 hours.

Systemic Observations and Body Weights:
There were no abnormal physical signs noted during the observation period

Other effects:

Systemic Observations and Body Weights:
There were no abnormal physical signs noted during the observation period. All body weight changes were normal.

Table1. Dermal Observations, Body Weights, and Systemic Observations
Rabbit Eartag	Animal Number
Rabbit Eartag	H3798	H3799	H3800
Sex	Male	Male	Male
Pre-test Body Weight (Kg)	2.7	2.9	3.0
Terminal Body Weight (Kg)	2.7	2.9	3.0
Erythema and Eschar Formation
Time after Patch Removal
60 minutes	2	2	2
24 hours	0	1	1
48 hours	0	0	1
72 hours	0	0	0
Edema
60 minutes	1	1	1
24 hours	1	1	1
48 hours	1	1	1
72 hours	0	0	0
Systemic Observations
60 minutes	A	A	A
24 hours	A	A	A
48 hours	A	A	A
72 hours	A	A	A

A = Normal

Interpretation of results:

GHS criteria not met

Remarks:

Not classified

Conclusions:

The test material Santiciser P1400 is a mild dermal irritant under the conditions of the study but does not meet the criteria for classification under EU CLP or GHS.

Executive summary:

The test material Santicizer Platinum P1400 was investigated to determine the irritant and corrosive effects when applied dermally for 4 hours. Three New Zealand rabbits were dosed dermally with 0.5 ml of the test material, which was applied and kept in contact to one skin site for 4 hours, at which time the wrapping was removed. The skin was evaluated for edema, erythema and scored at 1, 24, 48 and 72 hr (numerical Draize technique) following the patch removal. Toxicological and pharmacological effects, body weight and mortality were also recorded.

The results of the study showed well defined erythema and very slight edema at 1hr after the 4 hour exposure. At 24 and 48 hours, slight erythema and very slight edema was observed. These effects were fully reversible in all 3 tested animals by 72 hours. No adverse clinical signs, abnormal body weight or mortality were observed during the study. In conclusion, the test material Santiciser P1400 is a mild dermal irritant but does not meet the criteria for classification under EU CLP or GHS.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Remarks:

In vivo study

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-08-11 to 2011-03-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

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:

Label Identity: Santicizer P-1400
Batch No: RP-620
Supplied by: Ferro Corporation
Data received: 08/19/2010
Storage: Room temperature and humidity
Description: Clear yellow liquid
Sample preparation: Te test article was used as received

Species:

rabbit

Strain:

New Zealand White

Remarks:

1 female and 2 males

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Myrtle's Rabbitry, Inc. Thompsons, TN
- Date received: 10/21/10
- Date of birth: 07/20/10
- Weight at study initiation: 2.7 -2.8 kg
- Housing: 1/ cage in suspended cages
- Diet ( ad libitum): Fresh PMI Rabbit Chow - daily
- Water: ad libitum
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): This parameter deviated from the standard protocol. This did not influence the study animals and the integrity of the study.
- Humidity (%): This parameter deviated from the standard protocol. This did not influence the study animals and the integrity of the study.
- Air changes (per hr): no info
- Photoperiod (hrs dark / hrs light): 12hr /12 hr

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Single 0.1 mL dose into eye

Observation period (in vivo):

1, 24, 48, 72 hours

Duration of post- treatment incubation (in vitro):

Not applicable

Number of animals or in vitro replicates:

Three rabbits: 2 males and 1 female

Details on study design:

SCORING SYSTEM: see attachment
TOOL USED TO ASSESS SCORE: sodium fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

1 Female and 2 Males

Time point:

24/48/72 h

Score:

0

Max. score:

80

Irritation parameter:

iris score

Basis:

mean

Remarks:

1 Female and 2 Males

Time point:

24/48/72 h

Score:

0

Max. score:

10

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

1 Female and 2 Males

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

1 Female and 2 Males

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Ocular finding
Treated eyes: There was no corneal opacity, iritis or conjunctival irritation at any observation period.
Control eyes: The control eyes appeared normal at all observation periods.

Other effects:

Systemic observation
There were no abnormal physical signs noted during the observation period.

Table 1. Ocular Findings, Systemic Observations, and Body Weights
Animal No. / Sex	Item	Tissue	Reading	1 hour	24 hours	48 hours	72 hours
H3811 / Male	A	Cornea	Opacity	0	0	0	0
	B	Cornea	Area	0	0	0	0
		1. Total = (A x B) x 5		0	0	0	0
	C	Iris		0	0	0	0
		2. Total = (C x 5)		0	0	0	0
	D	Conjunctiva	Redness	0	0	0	0
	E		Chemosis	0	0	0	0
	F		Discharge	0	0	0	0
		3. Total = (D+E+F) x 2		0	0	0	0
		Total = 1+2+3		0	0	0	0
		Systemic Observations		A	A	A	A
		Sodium Fluorescein			0	N/A	N/A
		Pretest Body Weight: 2.7 Kg

H3812 / Male	A	Cornea	Opacity	0	0	0	0
	B	Cornea	Area	0	0	0	0
		1. Total = (A x B) x 5		0	0	0	0
	C	Iris		0	0	0	0
		2. Total = (C x 5)		0	0	0	0
	D	Conjunctiva	Redness	0	0	0	0
	E		Chemosis	1	0	0	0
	F		Discharge	1	0	0	0
		3. Total = (D+E+F) x 2		4	0	0	0
		Total = 1+2+3		4	0	0	0
		Systemic Observations		A	A	A	A
		Sodium Fluorescein			0	N/A	N/A
		Pretest Body Weight: 2.7 Kg

H3837 / Female	A	Cornea	Opacity	0	0	0	0
	B	Cornea	Area	0	0	0	0
		1. Total = (A x B) x 5		0	0	0	0
	C	Iris		0	0	0	0
		2. Total = (C x 5)		0	0	0	0
	D	Conjunctiva	Redness	0	0	0	0
	E		Chemosis	0	0	0	0
	F		Discharge	0	0	0	0
		3. Total = (D+E+F) x 2		0	0	0	0
		Total = 1+2+3		0	0	0	0
		Systemic Observations		A	A	A	A
		Sodium Fluorescein			0	N/A	N/A
		Pretest Body Weight: 2.8 Kg

A = Normal

The control eyes appeared normal at all observation points

Table 2. Mean scores (EU and GHS)
Time Points	24 hours	48 hours	72 hours	Mean
Animal Number / Sex	H3811 / Male
Corneal Opacity	0	0	0	0.0
Iritis	0	0	0	0.0
Conjunctival Redness	0	0	0	0.0
Conjunctival Edema (chemosis)	0	0	0	0.0

Animal Number / Sex	H3812 / Male
Corneal Opacity	0	0	0	0.0
Iritis	0	0	0	0.0
Conjunctival Redness	0	0	0	0.0
Conjunctival Edema (chemosis)	0	0	0	0.0

Animal Number / Sex	H3837 / Female
Corneal Opacity	0	0	0	0.0
Iritis	0	0	0	0.0
Conjunctival Redness	0	0	0	0.0
Conjunctival Edema (chemosis)	0	0	0	0.0

Interpretation of results:

GHS criteria not met

Remarks:

Not irritating

Conclusions:

Based on the lack of effects observed, It was determined that the test material Santicizer P1400 did not produce irritation to eyes and does not meet the criteria for classification as an ocular irritant under GHS or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Executive summary:

In a key EPA OPPTS Guideline 870.2400 study, the potential of the test material (Santicizer P1400) to cause ocular irritation or corrosion was evaluated after instillation into the rabbit eye. 0.1 mL of the test material was placed into the conjunctival sac of one eye of three healthy New Zealand White rabbits (1 female and 2 males) with the contralateral eye serving as control. Treated and control eyes were examined pretest and scored by the Draize technique at 1, 24, 48, and 72 hours post-exposure. Sodium fluorescein dye procedures were used at the 24 hour observation interval and animals were evaluated for mortality, toxicity, and pharmacological effects at each ocular observation point. Body weights were recorded pretest.

No abnormal physical signs were observed during the study period and no corneal opacity, iritis, or conjunctival irritation was observed at any observation point. In 1 animal at the 1 hour timepoint, chemosis (1) and discharge (1), without redness (0) was observed. However, this was fully reversible by 24 hours and not considered indicative of irritation by the test material. All control eyes appeared normal through the study period.

Based on the lack of effects observed, It was determined that the test material Santicizer P1400 did not produce irritation to eyes and does not meet the criteria for classification as an ocular irritant under GHS or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin Irritation

The test material Santicizer Platinum P1400 was investigated to determine the irritant and corrosive effects when applied dermally for 4 hours (MB Research Laboratories, 2011c). Three New Zealand rabbits were dosed dermally with 0.5 ml of the test material, which was applied and kept in contact to one skin site for 4 hours, at which time the wrapping was removed. The skin was evaluated for edema, erythema and scored at 1, 24, 48 and 72 hr (numerical Draize technique) following the patch removal. Toxicological and pharmacological effects, body weight and mortality were also recorded.

The results of the study showed well defined erythema and very slight edema at 1hr after the 4 hour exposure. At 24 and 48 hours, slight erythema and very slight edema was observed. These effects were fully reversible in all 3 tested animals by 72 hours. No adverse clinical signs, abnormal body weight or mortality were observed during the study. In conclusion, the test material Santiciser P1400 is a mild dermal irritant but does not meet the criteria for classification under EU CLP or GHS.

Based on the lack of effects observed, it was determined that the test material Santicizer P1400 does not meet the criteria for classification as a dermal irritant under GHS or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Eye Irritation

In a key read across EPA OPPTS Guideline 870.2400 study, the potential of the test material (Santicizer P1400) to cause ocular irritation or corrosion was evaluated after instillation into the rabbit eye (MB Research Laboratories, 2011d). 0.1 mL of the test material was placed into the conjunctival sac of one eye of three healthy New Zealand White rabbits (1 female and 2 males) with the contralateral eye serving as control. Treated and control eyes were examined pretest and scored by the Draize technique at 1, 24, 48, and 72 hours post-exposure. Sodium fluorescein dye procedures were used at the 24 hour observation interval and animals were evaluated for mortality, toxicity, and pharmacological effects at each ocular observation point. Body weights were recorded pretest.

No abnormal physical signs were observed during the study period and no corneal opacity, iritis, or conjunctival irritation was observed at any observation point. In 1 animal at the 1 hour timepoint, chemosis (1) and discharge (1), without redness (0) was observed. However, this was fully reversible by 24 hours and not considered indicative of irritation by the test material. All control eyes appeared normal through the study period.

Based on the lack of effects observed, it was determined that the test material Santicizer P1400 did not produce irritation to eyes anddoes not meet the criteria for classification as an ocular irritant under GHS or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

P1400 does not meet the criteria for classification as a dermal or ocular irritant under EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.