1,2-Cyclohexanedicarboxylic Acid, 1-(phenylmethyl) ester, ester with 2,2,4-trimethyl, 1,3-petanediol mono(2-methyl propanoate)

Skin irritation / corrosion

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

1,2-Cyclohexanedicarboxylic Acid, 1-(phenylmethyl) ester, ester with 2,2,4-trimethyl, 1,3-petanediol mono(2-methyl propanoate)

EC Number:

950-347-5

Cas Number:

1661012-65-2

Molecular formula:

C27H40O6

IUPAC Name:

1,2-Cyclohexanedicarboxylic Acid, 1-(phenylmethyl) ester, ester with 2,2,4-trimethyl, 1,3-petanediol mono(2-methyl propanoate)

Test material form:

liquid

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

Test animals

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.

Test system

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.

Results and discussion

In vivo

Results

Results 1

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

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.