Santicizer 2148

Endpoint summary

Description of key information

Skin Irritation:

Test material produced mild but generally reversible dermal irritation. The average dermal irritation score of XP-2563 is 2.1. Not classified as a dermal irritant under EU CLP but classified as Category 3 (mild irritant) under UN GHS.

Eye Irritation:

Test material produced mild, transient ocular irritation Not classified as an ocular irritant under EU CLP or UN GHS.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-11-14 to 1990-04-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Version / remarks:

FIFRA: Pesticide Assessment Guidelines (Primary Dermal Irritation Study);
TSCA: Health Effects Test Guidelines (Acute Exposure, Primary Dermal Irritation)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

6 (3 males 3 females) young adults (at least 8 weeks old at study initiation) Albino rabbits (New Zealand White) were chosen for dermal irritation studies. The New Zealand White breed was used because of its historical and because of the existing historical database for comparative evaluation. All animals were checked for viability twice daily. Prior to assignment to study all animals were examined to ascertain suitability for study.
The rabbits were individually housed in suspended, stainless steel with wire mesh bottoms in a temperature (60-70°F – monitored and recorded twice daily) and humidity (30-70% - monitored and recorded daily) controlled room with a 12 hour light, 12 hour dark cycle controlled by an automatic timer.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 mL of test material per site (the material was applied to two intact sites on eachO animal)

Duration of treatment / exposure:

single 4 hour exposure

Observation period:

7-14 days

Number of animals:

6

Details on study design:

On the day before dosing, the hair of each rabbit was clipped from the dorsal area of the trunk with an electric clipper so as to expose at least 10% of the body surface area, Care was taken to avoid abrading the skin. Only animals with intact, healthy skin were used.

The test material was administered as received. An appropriate amount of the test material was applied beneath a gauze square 1'' x 1'', placed directly on the test site and held in place with tape and a semi-occlusive covering. Elizabethean collars were placed on each animal prior to or at the time of dosing in order to prevent the animal from disturbing the wrapping and test sites.

Following 4 hours of exposure, the wrappings and gauze squares were removed and the test site was gently wiped free of excess test material using water and gauze. After approximately 30 minutes, dermal observations were made and scoring done according to the method of Draize.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24/72 hr

Score:

2.1

Reversibility:

not fully reversible within: 14 days

Remarks:

5 of the 6 animals were free of signs of dermal irritation. 1 animal continued to exhibit very slight (barely perceptible) dermal irritation at study termination.

Remarks on result:

probability of mild irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

4

Irritant / corrosive response data:

All six animals exhibited slight erythema with little or no edema. By Day 14, 5 of the 6 animals were free of signs of dermal irritation while 1 animal continued to exhibit very slight (barely perceptible) dermal irritation at study termination.

Table 1. Primary dermal irritation study in rabbits (4-hour exposure/semi-occlusive covering)

Time interval^b	Patch Sites & Observations		Animal Number and Sex						Mean Score
			8648F	8649M	8650F	8651M	8652F	8563M
0.5 Hours	Right	ER	0	1	1	0	1	0	-
		ED	0	0	0	0	0	0
		Other	-	-	-	-	-	-
	Left	ER	0	1	0	0	1	0
		ED	0	0	0	0	0	0
		Other	-	-	-	-	-	-
24 Hours	Right	ER	2	2	2	2	2	2	2.0
		ED	0	0	0	0	0	0	0.0
		Other	-	-	-	-	-	-	-
	Left	ER	2	2	2	2	2	2	2.0
		ED	0	1	0	0	0	1	0.3
		Other	-	-	-	-	-	-	-
48 Hours	Right	ER	2	2	2	2	2	2	-
		ED	0	0	0	0	0	0
		Other	-	-	-	-	-	-
	Left	ER	2	2	2	2	2	2
		ED	0	0	0	0	0	0
		Other	-	-	-	-	-	-
72 Hours	Right	ER	2	2	2	2	2	2	2.0
		ED	0	0	0	0	0	0	0.0
		Other	-	-	-	-	-	-	-
	Left	ER	2	2	2	2	2	2	2.0
		ED	0	0	0	0	0	0	0.2
		Other	-	-	-	-	-	-	-
Day 7	Right	ER	2	0	0	2	2	2	N/A
		ED	0	0	0	0	0	0
		Other	D	-	-	-	-	-
	Left	ER	2	0	0	2	2	1
		ED	0	0	0	0	0	0
		Other	0	-	0	-	-	-
Day 10	Right	ER	0	-	-	1	0	1
		ED	0	-	-	0	0	0
		Other	D	-	-	-	-	-
	Left	ER	0	-	-	1	0	1
		ED	0	-	-	0	0	0
		Other	D	-	-	-	-	-
Day 14	Right	ER	-	-	-	1	-	0
		ED	-	-	-	0	-	0
		Other	-	-	-	-	-	-
	Left	ER	-	-	-	0	-	0
		ED	-	-		0	-	0
		Other	-	-		0	-	-

^b Time indicated is time from patch removal

M = male; F = female; ER = Erythema; ED = Edema; D = Desquamation

Sum of means = 8.5

Average Dermal irritation score = 2.1

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

All 6 animals exhibited slight erythema with little or no edema. By Day 14, 5 of 6 animals were free of signs of dermal irritation; one animal continued to exhibit very slight (barely perceptible) dermal irritation at study termination (Day 14)

It was therefore concluded that XP-2563 produced mild by generally reversible dermal irritation. The average dermal irritation score of XP-2563 is 2.1 Animal experience or test data that indicates that the substance/mixture causes reversible damage to the skin following exposure of up to 4 hours, mean value of ≥1.5 < 2.3 for erythema/eschar in 2 of 3 tested animals.

Executive summary:

This study was intended to provide information on the health hazards likely to arise from a short-term accidental exposure to the test material by the dermal route. 6 (3 males 3 females) young adults (at least 8 weeks old at study initiation) Albino rabbits (New Zealand White) were chosen for dermal irritation studies. XP-2563 was applied to two intact sites on each animal, with a dosage of 0.5 ml per site, for an exposure period of approx. 4 hours under semi-occlusive conditions.

The results showed that all 6 animals exhibited slight erythema with little or no edema. By Day 14, five of six animals were free of signs of dermal irritation; one animal continued to exhibit very slight (barely perceptible) dermal irritation at study termination (Day 14)

It was therefore concluded that XP-2563 produced mild by generally reversible dermal irritation. The average dermal irritation score of XP-2563 is 2.1.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-11-14 to 1990-01-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

not specified

GLP compliance:

not specified

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
Source: Monsanto Company
Lot/batch no: 4321285
Purity: Not stated/determined

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Summit View Farm, Hazleton, Pennsylvania
- Age at study initiation: Young Adults
- Housing: Individually housed in suspended stainless steel cages with wire mesh bottom
- Diet (e.g. ad libitum): Lab rabbit chow HF ad libitum
- Water (e.g. ad libitum): Automatic watering system ad libitum
- Acclimation period: 62 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-21°C (given as 60-70°F)
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

IN-LIFE DATES: From: 14/11/89 To: 18/01/90

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

0.1 ml was introduced into the lower conjunctival sac of the right eye of each animal. The upper and lower lids were gently held together for 1 second prior to releasing to prevent loss of material. No wash was performed after application, however, ~24 hours after application the treated eye was rinsed to remove any residual test material

Observation period (in vivo):

All animals were checked for viability twice daily.
Ocular irritation was evaluated at 1, 24, 48, and 72 hours after treatment.

Number of animals or in vitro replicates:

6 (4 males, 2 females)

Details on study design:

On the day before dosing, both eyes of each animal were examined using fluorescein dye to check for presence of corneal ulceration. Just prior to test material application, the eyes were examined again without fluorescein. Animals showing pre-existing corneal or conjunctival injury or irritation were not placed on study.

A single dose of 1 ml was administered to the lower conjunctival sac of the right eye of each animal. The upper and lower lids were gently held together for 1 second prior to releasing to prevent loss of material. The left eye served as the control. The treated eyes were washed 24 hours after application to remove residual test material.

Scores were given for treated eyes according to EPA testing guidelines, included in appendix A of the report. "Eye irritation" is the production of reversible changes in the eye following application of test material to the anterior surface of the eye. "Eye corrosio" is the production of irreversible tissue damage in the eye following application of test material to the anterior surface of the eye. Fluorescein dye was used to confirm presence or absence of corneal ulceration in treated eyes starting with the 24 hour observation and at each subsequent observation until there was no stain retention for 2 observations.

Irritation parameter:

conjunctivae score

Remarks:

Redness; Discharge

Basis:

animal #1

Remarks:

No. 8655

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness; Discharge

Basis:

animal #2

Remarks:

8659

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness; Discharge

Basis:

animal #3

Remarks:

8658

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness; Discharge

Basis:

animal #4

Remarks:

8659

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness; Discharge

Basis:

animal #5

Remarks:

8660

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness; Discharge

Basis:

animal #6

Remarks:

8661

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

iris score

Basis:

mean

Remarks:

Animals 1-6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

Animals 1-6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

Animals 1-6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Conjunctival irritation (redness, chemosis, discharge) in all animals at 1 hour, redness present in 1 male at 24 and 48 hours. 2 males exhibited slight dulling of cornea at 1 hour but recovered by 24 hours. No significant corneal or iridial changes were seen. All 6 animals were free of ocular irritation 24-72 hours after instillation of test material.

Scores are given for treated eyes. Unless otherwise noted, control (untreated) eyes had negative scores for all parameters. Scored according to scale presented in the scoring system presented in the section 'Any other information on materials and methods incl. tables'.

 

Table 1. Eye Irritation study in rabbits- individual ocular scores

	Time after Administration (Hours)
	1	24	48	72	Positive scores
Animal No. 8655 M
1.
A.	1	0	0	0	No
B.	1	0	0	0	No
C.	2	0	0	0	No
D.	0	0	0	0	No
2.	0	0	0	0	No
3.
A.	0	0	0	0	No
B.	0	0	0	0	No
C.	0	0	0	0	No
D.	0	0f	0f	0	No
Animal No. 8657 M
1.
A.	1	0	0	0	No
B.	1	0	0	0	No
C.	1	0	0	0	No
D.	0	0	0	0	No
2.	0	0	0	0	No
3.
A.	+	0	0	0	No
B.	4	0	0	0	No
C.	0	0	0	0	No
D.	0	0f	0f	0	No
Animal No. 8658 F
1.
A.	1	0	0	0	No
B.	1	0	0	0	No
C.	2	0	0	0	No
D.	0	0	0	0	No
2.	0	0	0	0	No
3.
A.	0	0	0	0	No
B.	0	0	0	0	No
C.	0	0	0	0	No
D.	0	0f	0f	0	No
Animal No. 8659 M
1.
A.	1	0	0	0	No
B.	1	0	0	0	No
C.	2	0	0	0	No
D.	0	0	0	0	No
2.	0	0	0	0	No
3.
A.	0	0	0	0	No
B.	0	0	0	0	No
C.	0	0	0	0	No
D.	0	0f	0f	0	No
Animal No. 8660 F
1.
A.	1	0	0	0	No
B.	1	0	0	0	No
C.	2	0	0	0	No
D.	0	0	0	0	No
2.	0	0	0	0	No
3. Cornea
A.	0	0	0	0	No
B.	0	0	0	0	No
C.	0	0	0	0	No
D.	0	0f	0f	0	No
Animal No. 8661 M
1.
A.	2	1	1	0	Yes
B.	1	0	0	0	No
C.	2	0	0	0	No
D.	0	0	0	0	No
2.	0	0	0	0	No
3.	Cornea
A.	+	0	0	0	No
B.	4	0	0	0	No
C.	0	0	0	0	No
D.	0	0f	0f	0	No

f - Observation confirmed with fluorescein

M - Male

F - Female

 

Table 2. Summary of responses

	Positive (+) or Negative (-) Scores*
	Cornea		Iris	Conjunctivae
	Opacity	Ulceration		Redness	Chemosis	Necrosis or Ulceration
8655 M	-	-	-	-	-	-
8657 M	-	-	-	-	-	-
8658 F	-	-	-	-	-	-
8659 M	-	-	-	-	-	-
8660 F	-	-	-	-	-	-
8661 M	-	-	-	+	-	-

* = Reference for positive and negative scores: See scoring system presented in the section 'Any other information on materials and methods incl. tables'.

M - Male

F - Female

Interpretation of results:

GHS criteria not met

Conclusions:

XP-2563 produced mild, transient ocular irritation.

Executive summary:

A key EPA OPPTS Guideline 81-4 study was conducted to evaluate the ocular irritation potential of the test material (XP-2563) in rabbits (Bio/dynamics Inc., 1990c). 0.1 mL of the test material was introduced into the lower conjunctival sac of the right eye of six New Zealand White albino rabbits (3/sex). The upper and lower eye lids were gently held together for one second prior to releasing to prevent loss of the test material. The contralateral eye served as the control.

No wash was performed subsequent to application but 24 hours post exposure, the treated eyes were rinsed to remove any residual test material. Eyes were evaluated and scored for ocular reactions at approximately 1, 24, 48, and 72 hours after treatment. Fluorescein dye was used to confirm presence or absence of corneal ulceration in treated eyes starting with the 24-hour observation and at each subsequent observation until there was no stain retention for two observations.

Irritation observed consisted primarily of conjunctival irritation (redness, chemosis, discharge) with most effects occurring at 1 hour. Two animals exhibited a slight dulling of the corneal surface but no significant corneal or iridial changes were observed. All six animals were free of ocular irritation within 24 to 72 hours post instillation of the test material.

It was concluded that the test material (XP-2563) produced mild, transient ocular irritation.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation

A key EPA OPPTS Guideline 81-5 study was conducted to provide information on the health hazards likely to arise from a short-term accidental exposure to the test material (XP-2563) by the dermal route (Bio/dynamics Inc., 1990b). Six (3 males 3 females) young adult (at least 8 weeks old at study initiation) Albino rabbits (New Zealand White) were chosen for dermal irritation studies. The test material was applied to two intact sites on each animal, with a dosage of 0.5 mL per site for an exposure period of approximately 4 hours under semi-occlusive conditions.

The results showed that all 6 animals exhibited slight erythema with little or no edema. By Day 14, five of six animals were free of signs of dermal irritation; one animal continued to exhibit very slight (barely perceptible) dermal irritation at study termination (Day 14)

It was therefore concluded that XP-2563 produced mild by generally reversible dermal irritation. The average dermal irritation score of XP-2563 is 2.1.

Eye Irritation

A key EPA OPPTS Guideline 81-4 study was conducted to evaluate the ocular irritation potential of the test material (XP-2563) in rabbits (Bio/dynamics Inc., 1990c). 0.1 mL of the test material was introduced into the lower conjunctival sac of the right eye of six New Zealand White albino rabbits (3/sex). The upper and lower eye lids were gently held together for one second prior to releasing to prevent loss of the test material. The contralateral eye served as the control.

No wash was performed subsequent to application but 24 hours post exposure, the treated eyes were rinsed to remove any residual test material. Eyes were evaluated and scored for ocular reactions at approximately 1, 24, 48, and 72 hours after treatment. Fluorescein dye was used to confirm presence or absence of corneal ulceration in treated eyes starting with the 24-hour observation and at each subsequent observation until there was no stain retention for two observations.

Irritation observed consisted primarily of conjunctival irritation (redness, chemosis, discharge) with most effects occurring at 1 hour. Two animals exhibited a slight dulling of the corneal surface but no significant corneal or iridial changes were observed. All six animals were free of ocular irritation within 24 to 72 hours post instillation of the test material.

It was concluded that the test material (XP-2563) produced mild, transient ocular irritation.

Justification for classification or non-classification

Santicizer 2148 Plasticizer does not meet the criteria for classification as a dermal irritant under EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. However, Santicizer 2148 Plasticizer meets the criteria for classification as Category 3 (mild irritant) under the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Santicizer 2148 Plasticizer does not meet the criteria for classification as an ocular irritant under EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 or the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).