Allyl 3-cyclohexylpropionate

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

The effects of vehicles on the human dermal irritation potentials of allyl esters

Author:

Politano VT, Isola DA, Lalko J, Api AM

Year:

2006

Bibliographic source:

International Journal of Toxicology 25(3), 183-193

Materials and methods

Endpoint addressed:

skin irritation / corrosion

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

patch test with different vehicles

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Allyl 3-cyclohexylpropionate

EC Number:

220-292-5

EC Name:

Allyl 3-cyclohexylpropionate

Cas Number:

2705-87-5

Molecular formula:

C12H20O2

IUPAC Name:

prop-2-en-1-yl 3-cyclohexylpropanoate

Method

Ethical approval:

not specified

Details on study design:

The study was conducted to determine whether different vehicles affect the skin irritation potential of five different allyl esters. The allyl esters tested were allyl amyl glycolate, allyl caproate, allyl (cyclohexyloxy)acetate, allyl cyclohexylpropionate, and allyl phenoxyacetate in the vehicles diethyl phthalate, 3:1 diethyl phthalate:ethanol, and 1:3 diethyl phthalate:ethanol at concentrations of 0.1%, 0.5%, 1.0%, and 2.0% (w/w). A modified cumulative irritation test was conducted in 129 human subjects. Test materials (0.3 ml) were applied under occlusion to skin sites on the back for 1 day (24 h) using Hill Top chambers. Irritation was assessed at 1, 2, 4, and 5 days following application of test materials.

Exposure assessment:

measured

Details on exposure:

TYPE OF EXPOSURE: Dermal; 25 mm Hill Top Chamber patches (Holl Top Research, Miamiville, OH)

TYPE OF EXPOSURE MEASUREMENT: Exposure pads

SCORING SYSTEM: Draize scoring system (Draize, Woodard, and Calvery 1944)

EXPOSURE LEVELS: 0.3 mL of the test material

EXPOSURE PERIOD: 24 hours

POSTEXPOSURE PERIOD: 48, 96 and 120 hours

DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES: 130 subjects meeting criteria for inclusion were enrolled and were randomly divided into five test groups containing 26 subjects (5 groups for each of 5 test items). Each subject received a single application of 20 patches, which included the test material at four concentrations in each vehicle, vehicle controls, and positive and negative controls.

Results and discussion

Results:

The cumulative irritation score (CIS: summe of the scores of postexposure period) varied greatly among the test materials, with allyl 3-cyclohexylpropionate causing less irritation than any other allyl ester. The highest irritation score observed for any of the allyl esters tested was 2. No irritation was observed with saline.

Applicant's summary and conclusion

Conclusions:

Allyl 3-cyclohexanepropionate induced little to no irritation with any of the vehicles.

Executive summary:

This study was conducted to determine whether different vehicles affect the skin irritation potential of five different allyl esters. The allyl esters tested were allyl amyl glycolate (AAG), allyl caproate (AC), allyl (cyclohexyloxy) acetate (ACA), allyl cyclohexylpropionate (ACP), and allyl phenoxyacetate (APA) in the vehicles diethyl phthalate (DEP), 3:1 diethyl phthalate:ethanol (3:1 DEP:EtOH), and 1:3 diethyl phthalate:ethanol (1:3 DEP:EtOH) at concentrations of 0.1%, 0.5%, 1.0% and 2.0% (w/w). 1.0% sodium lauryl sulfate in distilled water, DEP, 3:1 DEP:EtOH, and 1:3 DEP:EtOH was the positive control. Each vehicle was tested as its own control and 100% physiological saline was the negative control. 130 subjects were enrolled in the study and 129 completed the study. One subject did not complete the study because patches did not remain on the back for the required 24 hour period. Subjects were randomly divided into five test groups containing 26 subjects. Test materials were applied using 25 mm Hill Top Chamber patches, which consisted of a flexible molded plastic chamber with a double rim that fits close to the skin. The chamber is lined with a nonwoven Webril pad, and the entire patch is held in place by semiocclusive tape. An aliquot of 0.3 ml of

the test material was dispensed onto the patch and the patch was affixed to the back of each subject. Each test material was tested in each vehicle at 0.1%, 0.5%, 1.0% and 2.0%. Each subject received a single application of 20 patches, which included the test material at four concentrations in each vehicle, vehicle controls, and positive and negative controls. The subjects were instructed not to expose thir backs to sunlight while on the study and to avoid excessive wetting while the patches were in place. After 1 day

(24 hrs), the subjects returned to the test facility and the patches were removed. Each patch area was rinsed with water and scored for irritation, using the Draize scoring system modified by Phillips et al (1972): 0 = no reaction; 1 = erythema throughout the entire patch area; 2 = erythema and edema; 3 = erythema, edema and vesicles; 4 = erythema, edema and bullae. Subjects were again evaluated 2, 4, and 5 days following patch application. The study was concluded after the day 5 laboratory visit. The irritation scores for each observation period were added to the scores from the previous observation periods to obtain a cumulative irritation score (CIS). The raw data were subjected to an analysis of variance (ANOVA). The calculated no-observed-effect-levels (NOELs) were determined by linear regression. Subjects: 129 Unspecified Sex Study Length: 24 hours Summary The test material, regardless of the vehicle used or concentration level, had no significant differences in the CIS. ACP had the highest CIS at 0.5 and 2.0% concentration when 1:3 DEP:EtOH was the vehicle. The NOELs for irritation, both the observed and calculated values were much lower when the vehicle was 1:3 DEP:EtOH. Irritant effects, concentrations were 0.1, 0.5, 1.0 and 2.0%. The test material, regardless of the vehicle used or concentration level, had no significant differences in the CIS. ACP had the highest CIS (2) at 0.5% and 2.0% concentration when 1:3 DEP:EtOH was the vehicle. CIS ranged from 0-1 in DEP and 3:1 DEP:EtOH and 0-2 in 1:3 DEP:EtOH. The NOELs for irritation, both the observed and calculated values were much lower when the vehicle was 1:3 DEP:EtOH (0.12 calculated/0.10 observed) vs 3:1 DEP:EtOH (0.40 calculated/1.00 observed) vs DEP (0.40 calculated/1.00 observed). ACP caused the least irritation of any ester tested.