Santicizer P1400

Endpoint summary

Description of key information

ACUTE ORAL

The potential for oral acute toxicity of the test material Santicizer Platinum P1400 was determined according the OECD 423 and OPPTT 870.1000 Testing Guidelines.

Three males and three females Sprague Dawley were dosed orally with 2000 mg/kg of Santicizer Platinum P1400. The single dose was based on the sample weight as calculated from the specific gravity. A single dose was administered orally by syringe and dosing needle.

The animals were observed for mortality, body weight changes, general toxicity and pharmacological effects. All animals survived until the end of the treatment. No abnormal physical signs nor changes in body weights related to the treatment were observed. The gross pathology were normal. Based on the results of this study, the LD50 was considered to be greater than 2000 mg/kg bw.

ACUTE DERMAL

The test article Santicizer Platinum P1400 was applied dermally to five male and female rabbits. The test material was kept in contact with the scin for 24 hours (semi- occlusive patch). The test sites were scored for dermal irritation at 24 hours post dose and on day 14 using numerical Draize scoring code below. The skin was evaluated for ulceration, necrosis and tissue destruction. Mortality, body weights, toxicit, pharmacologic effects were recorded. The results of the study showed incidence of few faces in two males and one female with soiling of the angemital area on day 14. Erythema was slight to well denined with very slight to sligh edema at 24 hours and by day 14 no erytthema was observed. The body weights were normal as well as the necropsy results. Based on the result of this study, the acute dermal toxicity LD50 of the test material Santicizer Platinum P 1400 is greater than 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

Identity: Santicizer Platinum P-1400
Batch:: RP-620
Supplier: Ferro Corporation
Date Received: 19 August 2010
Storage: Room temperature and humidity
Description: Clear yellow liquid
Specific gravity: 1.05
Sample Preparation: Used as received

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Boyertown, PA on 11/09/10
- Age at study initiation: Born on 09/14/10
- Weight at study initiation: 179-184 grams for males and 291-324 for females
- Fasting period before study: 16-20 hours prior dosing
- Housing: suspended wire cages
- Diet (e.g. ad libitum): Fresh PMI Rat Chow (Diet#5012) was freely available except for 16-20 hours prior dosing
- Water (e.g. ad libitum): freely available
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): parameters deviated from protocol - not adverse effect on the study animals or the integrity of the study
- Humidity (%): parameters deviated from protocol - not adverse effect on the study animals or the integrity of the study
- Air changes (per hr): no info
- Photoperiod (hrs dark / hrs light): 12 hr light/12 hr dark

TEST DATES:
Study initiation: 08 November 2010
Experimental Start Date: 17 November 2010
Experiment Term date: 06 December 2010
Draft Report Signed: 06 January 2011
Final Report Signed: 03 March 2011

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2000 mg/kg
- The test article was used as received and the dose was based on the sample weight as calculated from the specific gravity.

Doses:

1 single dose: 2000 mg/kg

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: half hr, 1, 2, 3 hr post dose and once daily for 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, toxicity and pharmacological effects

Statistics:

Not available

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived the 2000 mg/kg oral dose

Clinical signs:

other: No abnormal physical signs were observed during the treatment

Gross pathology:

No effects

Other findings:

No additional observations

Table 1. Body Weights and Dose Volume
Animal No.		Sex	Dose Volume (mL)	Body Weight (g)
				Day 0	Day 7	Day 14
1		Female	0.34	179	246	262
2		Female	0.34	180	238	265
3		Female	0.35	184	243	277
Mean				181	242	268
S.D.				2.6	4.0	7.9
#				3	3	3
4	Male		0.61	320	384	418
5	Male		0.62	324	399	437
6	Male		0.55	291	363	398
Mean				312	382	418
S.D.				18.0	18.1	19.5
#				3	3	3

Table 2. Necropsy Observations
Animal Number	1	2	3	4	5	6
Sex	Female	Female	Female	Male	Male	Male
Death (D) / Sacrifice (S)	S	S	S	S	S
Observation
Appeared normal / No findings	X	X	X	X	X	X

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Based on the results observed, the LD50 of the test material Santicizer Platinum P1400 was determined to be greater than 2000 mg/Kg body weight in rats.

Executive summary:

The potential for oral acute toxicity of the test material Santicizer Platinum P1400 was determined according the OECD 423 and OPPTS 870.1000 Testing Guidelines. Three males and three females Sprague Dawley were dosed orally with 2000 mg/Kg of Santicizer Platinum P1400. The single dose was based on the sample weight as calculated from the specific gravity. A single dose was administered orally by syringe and dosing needle.

The animals were observed for mortality, body weight changes, general toxicity and pharmacological effects. All animals survived until the end of the treatment. No abnormal physical signs nor changes in body weights related to the treatment were observed. The gross pathology were normal. Based on the results of this study, the LD₅₀ was considered to be greater than 2000 mg/Kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Adequate

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
Due to the physicochemical properties, exposure by inhalation is absent.

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Due to the physicochemical properties, exposure by inhalation is absent.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Identity: Santicizer P-1400
Batch No: RP-620
Supplied by: Ferro Corporation
Data received: 09/19/2010
Storage: Room temperature and humidity
Description: Clear yellow liquid
Specific gravity: 1.05
Sample Preparation: The test article was used as received

TEST DATES:
Study Initiation: 08 November 2010
Experimental Start Date: 10 November 2010
Experimental Term Date: 24 November 2010
Draft Report Signed: 07 January 2011
FInal Report Signed: 03 March 2011

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Myrtle's Rabbitry Incorporated, Thompson Statio, TN
- Received on: 10/21/10
- Date of birdh: 07/20/10
- Weight at study initiation: 2.4-2.9 Kg for males and 2.8-3.0 Kg for females
- Housing: 1/cage in suspended cages
- Diet (e.g. ad libitum): PMI Rabbit Chow - daily
- Water (e.g. ad libitum): freely available
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): parameters deviated from protocol - no adverse effect on the study animals or the integrity of the study
- Humidity (%): parameters deviated from protocol - no adverse effect on the study animals or the integrity of the study
- Air changes (per hr): no info
- Photoperiod (hrs dark / hrs light): 12 hr dark/12 hr light

Type of coverage:

semiocclusive

Vehicle:

not specified

Details on dermal exposure:

TEST SITE
- Area of exposure: 10x15 cm
- % coverage: 10%
- Type of wrap if used: piece of porous dressing (semi occlusive)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): water distillated
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

Single Dose of 2000 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1, 4 hours post dosing and once daily until Day 14
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, toxicity, pharmacological effects, gross pathology

Statistics:

An estimate of the LD50 was made based on the mortality occurring during the study.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived until the end of the study.

Clinical signs:

other: Few feces were observed in two males and one female was observed with soiling of the anogenital area on day 14. No other observation.

Gross pathology:

Necropsy did not reveal any treatment-related changes.

Other findings:

Erythema was slight to well defined with very slight to slight edema at 24 hours and by day 14 there was no erythema or edema observed.

Table 1. Body Weights and Dose Volume
Animal No.	Sex	Dose Volume (mL)	Body Weight (Kg)
			Day 0	Day 7	Day 14
H3813	Male	5.5	2.9	3.0	3.1
H3842	Male	4.6	2.4	2.6	2.6
H3816	Male	5.3	2.8	2.9	3.0
H3802	Male	5.3	2.8	3.0	3.0
H3803	Male	5.3	2.8	2.9	3.0
Mean			2.7	2.9	2.9
S.D.			0.2	0.2	0.2
#			5	5	5
H3829	Female	5.7	3.0	3.2	3.1
H3830	Female	5.3	2.8	3.0	3.2
H3831	Female	5.3	2.8	3.0	3.0
H3824	Female	5.5	2.9	2.9	3.1
H3825	Female	5.3	2.8	3.0	3.2
Mean			2.9	3.0	3.1
S.D.			0.1	0.	0.1
#			5	5	5

Table 2. Dermal Observations
Time Periods		Animal Number and Sex
		Male					Female
		H3813	H3842	H3816	H3802	H3803	H3829	H3830	H3831	H3824	H3825
24-hour	Erythema	2	2	1	1	2	2	1	2	1	2
	Edema	2	1	2	2	1	0	1	2	2	1
Day 14	Erythema	0	0	0	0	0	0	0	0	0	0
	Edema	0	0	0	0	0	0	0	0	0	0

Table3. Necropsy Observations
Animal Number	H3813	H3842	H3816	H3802	H3803	H3829	H3830	H3831	H3824	H3825
Sex	Male					Female
Death (D) / Sacrifice (S)	S	S	S	S	S	S	S	S	S	S
Observation
Normal	X	X	X	X	X		X	X	X	X
Anogenital area: soiled						X

X: Observed

Interpretation of results:

other: Not classified

Conclusions:

Based on the results observed, the dermal LD50 of Santicizer P1400 was determined to be greater than 2000 mg/Kg of body weight in rabbits. According to GHS Classification, Santicizer P1400 meets the criteria to be classified as Acute Toxic Category 5.

Executive summary:

A key EPA Guideline OPPTS 870.1200 study was conducted to determine the potential for toxicity of the test material (Santicizer P1400) when applied dermally. Five male and five female New Zealand White rabbits were dosed dermally with Santicizer P1400 at 2000 mg/Kg of body weight. The test material was kept in contact with the skin for 24 hours and dermal responses recorded at 24 hours post exposure and on Day 14. Animals were observed for toxicity, mortality and pharmacological effects at 1 and 4 hours post exposure and once daily for 14 days. Body weights were recorded pretest, weekly and at termination and all animals were examined for gross pathology.

 

No mortality was observed through the study period. Incidences of few faeces were observed in two males while one female was observed to have soiling of the anogenital area on Day 14. No other physical signs were observed. At 24 hours post exposure, erythema was slight to well-defined and edema was very slight to slight. By Day 14, no erythema or edema was observed. Body weight changes in all animals in both sexes appeared normal and gross necropsy revealed no remarkable findings.

 

Based on the results observed, the dermal LD₅₀ of Santicizer P1400 was determined to be greater than 2000 mg/Kg of body weight in rabbits. According to GHS Classification, Santicizer P1400 meets the criteria to be classified as Acute Toxic Category 5.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Adequate for assessment

Justification for classification or non-classification

P1400 is not classified as hazardous according to the CLP regulation.