Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Adequate substance specific and read across data are available for assessing the skin irritation and eye irritation potential of Santicizer P1700.

Skin Irritation: Not a dermal irritant

Ocular Irritation: Not an ocular irritant

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08/06/2015-16/09/2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
At the request of the sponsor additional analysis was conducted according to the currrent Globally Harmonized System of Classification and Labelling of Chemicals
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Label Identity: Santicizer P-1700
Batch No: VSC1002-2
Supplied by: Valerus Specialty Chemicals
Data received: 12/05/15
Storage: Room temperature and humidity
Description: Clear light-yellow liquid
Species:
rabbit
Strain:
New Zealand White
Remarks:
1 male & 2 female
Details on test animals or test system and environmental conditions:
Animals were received from Covance Research Products Inc Denver PA on 06 May 2015 and 20 May 2015. Following an acclimation period of at least 5 days, three healthy New Zealand White Rabbits (one male - two females) were selected from a larger group without conscious bias. The animals were born on 04 Oct 2014 and 03 Jan 2015. The pretest body weight was 3.0-3.2kg. The animals were identified by cage notation and a uniquely numbered metal eartag, and individually housed in suspended wire bottom cages. Absorbent paper bedding was placed beneath the cages and changed at least 3x per week. Fresh PMI Rabbit Chow (Diet #5321) was provided daily. Water was available ad libitum. The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12-hr light/dark cycle and was kept clean and vermin free.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5ml per site of test article (as supplied) was dosed under a 2cm x 3 cm gauze patch secured with non-irritating tape. Gentle pressure was applied to aid in the distribution of the test article over the prepared site. The torso was covered with a piece of porous dressing (semi- occlusive) large enough to cover the dose site with a least 5 cm squared to spare on all sides of the gauze patch. Porous, non-irritating tape was used to encircle the trunk of the animal. The test article was kept in contact with the skin for 4hr at which time the wrappings and patches were removed.
Duration of treatment / exposure:
4 hr
Observation period:
1, 24, 48 and 72 hours for all 3 animals, 7 and 14 days for two of these animals.
Number of animals:
1 male 2 females
Details on study design:
The test sites were scored for dermal irritation at 1, 24, 48 and 72hr for all animals and again on days 7 and 14 for two of these animals. Erythema and oedema were scored (0-4) according to the numerical Draize technique. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Body weights were recorded pretest and at termination.

Animals were observed for toxicological and pharmacological effects at each dermal absorption period and observed for mortality daily. All animals were humanely sacrificed using CO2 at study termination.Dermal irritation and corrosion were classified according to GHS criteria.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Very slight to well-defined erythema was observed between 1 hour and Day 7 post exposure to the test material. This was seen to be completely reversed by Day 14 of the study period. Absent to very slight edema was observed between 1 and 48 hours post exposure to the test material . No edema was observed at the 72 hour observation point. 

Skin irritation data is presented in Table 1 in the section 'Any other information on results incl. tables'.
Other effects:
There were no abnormal physical signs observed upon systemic evaluation.

Two animals gained weight by study termination. One animal's weight remained the same.

Table 1. Dermal Observations, Body Weights, and Systemic Observations

Rabbit Eartag

Animal Number

H7705

H7698

H7699

Sex

Male

Female

Female

Pre-test Body Weight (Kg)

3.0

3.0

3.2

Terminal Body Weight (Kg)

3.2

3.0

3.3

Erythema and Eschar Formation

Time after Patch Removal

 

 

 

60 minutes

1

1

1

24 hours

2

2

1

48 hours

1

1*

1

72 hours

1

0

1

 7 days

1

NA

1

14 days

0

NA

0

Edema

60 minutes

1

0

0

24 hours

2

0

1

48 hours

1

0

0

72 hours

0

0

0

7 days

0

NA

0

14 days

A

NA

0

Systemic Observations

60 minutes

A

A

A

24 hours

A

A

A

48 hours

A

A

A

72 hours

A

A

A

7 days

A

NA

A

14 days

A

NA

A

A =Appeared Normal

NA = Not Applicable

* = Reclipped

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results observed,Santicizer P1700 does not meet the criteria for classification as a skin 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 870.2500 study, three New Zealand White rabbits (one male and two female) were dermally exposed to the test material Santicizer P1700. 0.5 mL of the test material was applied dermally to one intact site per rabbit and kept in contact with the skin for a period of 4 hours under semi-occlusive wrap. Erythema and edema were scored at 1, 24, 48, and 72 hours for all animals and then again on days 7 and 14 for two animals. The skin of animals was also evaluated for ulceration and necrosis or for any evidence of tissue destruction. Animals were observed for toxicological and pharmacological effects for each dermal observation period and observed daily for mortality while body weights were recorded pretest and at termination.

 

There were no abnormal physical signs observed upon systemic evaluation. Two animals gained weight by study termination while one animal's weight remained the same. Very slight to well-defined erythema was observed between 1 hour and Day 7 post exposure to the test material. This was seen to be completely reversed by Day 14 of the study period. Absent to very slight edema was observed between 1 and 48 hours post exposure to the test material . No edema was observed at the 72 hour observation point. 

 

Based on the results observed,Santicizer P1700 does not meet the criteria for classification as a skin irritant under GHS or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.


Endpoint:
skin irritation / corrosion, other
Remarks:
In vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Only available as a brief summary report
Justification for type of information:
The justification for read across is provided as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
no guideline followed
Principles of method if other than guideline:
The undiluted test material was applied (occluded) to the skin of rabbits for 24 hours, and the skin was subsequently assessed for signs of irritation over a period of a week.
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Probably New Zealand white
Details on test animals or test system and environmental conditions:
no data
Type of coverage:
occlusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
no data
Duration of treatment / exposure:
24 hours
Observation period:
One week
Number of animals:
Two females and one male
Details on study design:
TEST SITE
- Type of wrap if used: "plastic strips" to retard evaporation and avoid contamination.
no further data


REMOVAL OF TEST SUBSTANCE
Test material removed after 24 hours, presumbaly by gentle washing but no details given.


SCORING SYSTEM: According to the method of Draize et al. (1944).
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24 h
Score:
ca. 0.6
Max. score:
8
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: mean 24/48/72 hours not specified
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: mean 24/48/72 hours not specified
Irritant / corrosive response data:
Barely perceptible redness was reported in two of the three rabbits examined 24-hours after removal of the test material, with an average maximum score of 0.6 out of a possible 8. No irritation was reported at the other time points (1, 48, 72, 120 and 168 hours after the end of exposure) with any of the three rabbits.
Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
A 24-hour covered application of undiluted Santicizer 278 was not irritating to the intact skin of three rabbits.
Executive summary:

Undiluted Santicizer 278 was applied to the clipped, intact skin of one male and two female albino rabbits, covered with "plastic strips", and removed after 24 hours. The animals were subsequently assessed for signs of irritation during the 7-day observation period, and the data scored according to the method of Draize.

Barely perceptible redness was reported in two of the three rabbits examined 24-hours after removal of the test material, with an average maximum score of 0.6 out of a possible 8. No irritation was reported at the other time points in any of the three rabbits. The investigators classed the test material as non-irritating when applied (occluded) to the intact skin of male and female rabbits. Under EC CLP regulations, this study would indicate that Santicizer 278 is not irritating to the skin.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because an acute toxicity study by the dermal route does not indicate skin irritation up to the relevant limit dose level (2 000 mg/kg body weight)
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
An in vitro study does not need to be conducted because an acute toxicity study by the dermal route does not indicate skin irritation up to the relevant limit dose. Please, see key study. Additionally, adequate in vivo skin irritation data is also available for assessment from studies conducted to fulfill requirements as mandated by the United States Environmental Protection Agency (US EPA).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09/06/2015-16/09/2015
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:
yes
Remarks:
Sodium fluorescein dye was used at 48 and 72hr after there was no stain retention at 24hr. No impact expected since the additional observations confirm no corneal opacity.
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
yes
Remarks:
Sodium fluorescein dye was used at 48 and 72hr after there was no stain retention at 24hr. No impact expected since the additional observations confirm no corneal opacity.
Principles of method if other than guideline:
Test article characterisation (Certificate of Analysis) not done to GLP by sponsor. No impact expected.

Sodium fluorescein dye procedures were performed at the 48 and 72 hour observation intervals after there was no stain retention at the 24 hour observation interval. No impact is expected since the additional information confirms there was no corneal opacity
GLP compliance:
yes
Specific details on test material used for the study:
Label Identity: Santicizer P-1700
Batch No: VSC1002-2
Supplied by: Valerus Specialty Chemicals
Data received: 12/05/15
Storage: Room temperature and humidity
Description: Clear light-yellow liquid
Species:
rabbit
Strain:
New Zealand White
Remarks:
1 female & 2 male
Details on test animals or tissues and environmental conditions:
Test Animals
New Zealand White rabbits were received from Covance Research Products, Inc., Denver, PA on 06 May 2015 and 20 May 2015 and acclimated for at least five days. Only animals in apparent good health were made available for study assignment. Prior to being selected for this study, both eyes of each animal were examined according to the Draize technique for any evidence of irritation or abnormalities of the cornea, iris and/or conjunctiva. A Mini-Maglite® flashlight equipped with a high intensity bulb was used
to aid in the examination. Three rabbits (one female - two males), free from evidence of ocular irritation or abnormalities, were assigned to this study without conscious bias. The animals were born on 04 Oct 2014 or 29 Nov 2014 and/or 03 Jan 2015. The pretest body weight range was 3.2 - 3.4 kg. The animals were identified by cage notation and a uniquely numbered metal eartag. The animals were housed one per cage in suspended cages. Absorbent paper bedding was placed beneath the cages and changed at least three times per week. Fresh PMI Rabbit Chow (Diet #5321) was provided daily. Water was available ad fib/turn. The animal room, reserved exclusively for
rabbits on acute tests, was temperature controlled, had a 12-hour light/dark cycle and was kept clean and vermin free.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
The test article (0.1 mL) was placed by syringe into the conjunctival sac that was formed by gently pulling the lower eyelid away from the eye. After instillation, the lids were held together for approximately one second to insure adequate distribution of the test article. One eye of each rabbit was dosed. The contralateral eye served as a control.
Duration of treatment / exposure:
Single 0.1 mL dose into eye, observed post-dosing for 72 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
1 female, 2 males
Details on study design:
Analgesic:
An analgesic. Buprenorphine was administered subcutaneously between the shoulder blades approximately 1.5 hours prior to instillation of the test article.

Dosing
The test article (0.1 n,I) was placed by syringe into the conjunctival sac that was formed by gently pulling the lower eyelid away from the eye. After instillation, the lids were held together for approximately one second to insure adequate distribution of the test article. One eye of each rabbit was dosed. The contralateral eye served as a control.

Type and Frequency of Observations
Using a Mini-Maglite® flashlight equipped with a high intensity bulb, the treated eye of each rabbit was examined for irritation of the cornea, iris and conjunctiva 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 24,48 and 72 hour observation intervals. The eye was examined with the aid of an tiltraviolet light source. Ocular reactions were graded according to the numerical Draize technique. Body weights were recorded pretest and at termination. Animals were evaluated for physical signs twice daily for the first three days of the study All animals were humanely sacrificed with a 1 ml intravenous injection (via the marginal ear vein) of Fatal-Plus following study termination.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
Female
Time point:
24/48/72 h
Score:
0
Max. score:
80
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
Male
Time point:
24/48/72 h
Score:
0
Max. score:
80
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
Male
Time point:
24/48/72 h
Score:
0
Max. score:
80
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
10
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
10
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
10
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
There was no corneal opacity or iritis noted at any time point. Conjunctival redness (grade 1) was noted in one out of three eyes at 24 hours, which cleared by 48 hours [and was considered not due to test material]. The control eyes were normal at all time points.
Other effects:
There were no abnormal physical signs noted during the observation period. One animal gained weight and two animals' weights remained the same.

Table 1. Mean scores (EU and GHS)

Time Points

24 hours

48 hours

72 hours

Mean

Animal Number / Sex

H7700 / 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

 

Animal Number / Sex

H7706 / Male

Corneal Opacity

0

0

0

0.0

Iritis

0

0

0

0.0

Conjunctival Redness

1

0

0

0.33

Conjunctival Edema (chemosis)

0

0

0

0.0

 

Animal Number / Sex

H7707 / 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

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the effects observed, Santicizer P1400 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. Santicizer P1700 meets the criteria for classification as Category IV (Minimal effects clearing in less than 24 hours) under the US Environmental Protection Agency system of classification for eye irritation.
Executive summary:

In a key OECD Guideline 405 study, the potential of the test material (Santicizer P1700) to cause ocular irritation or corrosion was evaluated after instillation into the rabbit eye. 1.5 hours prior to exposure, an analgesic, Buprenorphine was administered subcutaneously between the shoulder blade of three healthy New Zealand White rabbits (1 female and 2 males). 0.1 mL of the test material was placed into the conjunctival sac of one eye of each of the three rabbits, 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, 48, and 72 hour observation intervals and 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.

 

No abnormal physical signs were observed during the study period and one animal gained weight while the weight of the remaining two animals remained the same. No corneal opacity or iritis was observed at any observation point and conjunctival redness was observed in one animal at the 24 hour observation point. However, this has cleared by the 48 hour observation point. No other treatment-related ocular effects were observed and all control eyes appeared normal through the study period.

 

Based on the effects observed, Santicizer P1400 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. Santicizer P1700 meets the criteria for classification as Category IV (Minimal effects clearing in less than 24 hours) under the US Environmental Protection Agency system of classification for eye irritation.


Endpoint:
eye irritation, other
Remarks:
In vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Only available as a brief summary report
Justification for type of information:
The justification for read across is provided as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
no guideline followed
Principles of method if other than guideline:
The undiluted test material was placed in the conjunctival sac of the right eye of each of three rabbits, and the eyes were rinsed after 24 hours and assessed for signs of inflammation over a period of a week.
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Probably New Zealand white
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
One week
Number of animals or in vitro replicates:
Two males and one female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm isotonic saline solution
- Time after start of exposure: 24 hours


SCORING SYSTEM: According to the method of Draize et al. (1944).

Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 hour
Score:
ca. 4
Max. score:
110
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: mean 24/48/72 hour scores not specified
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: mean 24/48/72 hour scores not specified
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: mean 24/48/72 hour scores not specified
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: mean 24/48/72 hour scores not specified
Irritant / corrosive response data:
Immediately after rinsing, little or no discomfort was observed. At 10 minutes and 1 hour after rinsing, barely perceptible erythema and slight discharge was seen (but no oedema), with an average score of 4 out of a possible 110 when examined at 1 hour post exposure. Eyes were described as normal when examined 24, 48, 72, 120 and 168 hours after rinsing.
Other effects:
no data
Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Slight eye irritation was seen shortly after undiluted Santicizer 278 was placed in the conjunctival sac of the right eye of each of three rabbits, and subsequently rinsed after 24 hours, although this had cleared 24 hours later.
Executive summary:

Undiluted Santicizer 278 (0.1 ml) was placed in the conjunctival sac of the right eye of three albino rabbits, and subsequently rinsed with warm saline after 24 hours. The treated eyes were assessed for signs of irritation during the 7-day observation period, and the data scored according to the method of Draize.

Immediately after rinsing, little or no discomfort was observed. However, at 10 minutes and 1 hour after rinsing, barely perceptible erythema and slight discharge was seen (but no oedema), with an average score of 4 out of a possible 110 when examined at 1 hour post exposure. Eyes were described as normal when examined 24, 48, 72, 120 and 168 hours after rinsing. The investigators classed the test material as a slight eye irritant in male and female rabbits. Under the EC CLP regulations, this study would indicate that Santicizer 278 is not irritating to the eyes.

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
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
Adequate in vivo eye irritation data is also available for assessment from studies conducted to fulfill requirements as mandated by the United States Environmental Protection Agency (US EPA).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Three healthy New Zealand White Rabbits (one male, two females) were dosed with the test article Santicizer P1700 with a semi-occlusive patch for 4-hours (MB Research Laboratories, 2015c).  The test sites were scored for dermal irritation at 1, 24, 48 and 72hr for all animals and again on days 7 and 14 for two of these animals. Erythema and oedema were scored (0-4) according to the numerical Draize technique. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Body weights were recorded pretest and at termination.

For all three animals up to 48hr, erythema was present – very slight (except 24hr – very slight to well defined), whereas edema was absent to slight. At 72 hr erythema was absent to very slight and edema was absent. For the two animals observed at 7 days, erythema was very slight and edema was absent; at 14 days both erythema and edema were absent. All effects were reversible. No abnormal physical signs were observed. One animal maintained weight and the other two gained weight by study termination. According to OECD and EPA guidelines, Santicizer P1700 is not a dermal irritant; by GHS it is unclassified.

Read across data is also available from the source dossier that tested Santicizer S278 (benzyl 3-(isobutyryloxy)-1-isopropyl-2,2-dimethylpropyl phthalate) based on analogue read across. A discussion and report on the read across strategy is provided as an attachment in Section 13 of the dossier.

When undiluted Santicizer 278 was applied (occluded) to the intact skin of one male and two female albino rabbits for 24 hours, barely perceptible redness (with an average maximum score of 0.6 out of a possible 8) was reported in two of the three rabbits examined 24 hours after removal of the test material. No irritation was reported at the other time points in any of the three rabbits. The investigators classed the test material as non-irritating when applied (occluded) to the intact skin of male and female rabbits (Younger Laboratories, 1969c).

Eye Irritation

In a key OECD Guideline 405 study, the potential of the test material (Santicizer P1700) to cause ocular irritation or corrosion was evaluated after instillation into the rabbit eye (MB Research Laboratories, 2015d). 1.5 hours prior to exposure, an analgesic, Buprenorphine was administered subcutaneously between the shoulder blade of three healthy New Zealand White rabbits (1 female and 2 males). 0.1 mL of the test material was placed into the conjunctival sac of one eye of each of the three rabbits, 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, 48, and 72 hour observation intervals and 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.

 

No abnormal physical signs were observed during the study period and one animal gained weight while the weight of the remaining two animals remained the same. No corneal opacity or iritis was observed at any observation point and conjunctival redness was observed in one animal at the 24 hour observation point. However, this has cleared by the 48 hour observation point. No other treatment-related ocular effects were observed and all control eyes appeared normal through the study period.

 

Based on the effects observed, Santicizer P1700 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. Santicizer P1700 meets the criteria for classification as Category IV (Minimal effects clearing in less than 24 hours) under the US Environmental Protection Agency system of classification for eye irritation.


Read across data is also available from the source dossier that tested Santicizer S278 (benzyl 3-(isobutyryloxy)-1-isopropyl-2,2-dimethylpropyl phthalate)based on analogue read across. A discussion and report on the read across strategy is provided as an attachment in Section 13 of the dossier.

When undiluted Santicizer 278 (0.1 ml) was placed in the eyes of one female and two male albino rabbits, and subsequently rinsed after 24 hours, slight or no discomfort was observed immediately after the 24-hour exposure period, and barely perceptible erythema and slight discharge (but no oedema) were seen with an average score of 4 out of a possible 110 when examined at 1-hour post exposure. Eyes were apparently unaffected by treatment when examined 24, 48, 72, 120 and 168 hours after rinsing, giving an overall irritation score of 0 (average of scores assessed at 24, 48 and 72 hours after rinsing). The investigators classed the test material as a slight eye irritant in rabbits (Younger Laboratories, 1969d).


Justification for classification or non-classification

P1700 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.