Tetradecan-1-ol, propoxylated, esters with propionic acid

Endpoint summary

Description of key information

An in vitro skin and eye irritation study do not need to be conducted because adequate data from in vivo skin irritation studies and an in vivo eye irritation study are available. The potential of PPG-2 myristyl ether propionate to provoke skin irritation in human participants was examined in a study that followed a protocol similar to the Human Repeated Insult Patch Test (HRIPT) by Draize et al. (1944) and Draize (1959). Under the conditions of the study, it was determined that the registered substance was not a skin irritant. An in vivo study with New Zealand albino rabbits based on an experimental procedure similar / equivalent to that of Draize et al. (1944) further confirmed no irritation to skin (abraded and non-abraded) following exposure to PPG-2 myristyl ether propionate. No irritation symptoms (e.g. lesions) to the cornea, iris, or conjunctivae of New Zealand rabbits were reported after a 0.1 ml single dose to the eye mucosa for a 24-hour exposure period, inferring that the registered substance does not possess ocular irritation potential. Classification as an irritant / corrosive material to the skin or eyes is not required (CLP Regulation (EC) No. 1272/2008).

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:

April 19, 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

other: Human Repeated Insult Patch Test (HRIPT)

Version / remarks:

Draize, J.H., Woodard, G., and Calvery, H.D. (1944). Methods for the Study of Irritation and Toxicology of Substances Applied Topically to the Skin and Mucous Membrane. Journal of Pharmacology and Experimental Therapeutics. 83, 377 - 90.

Qualifier:

equivalent or similar to guideline

Guideline:

other: Human Repeated Insult Patch Test (HRIPT)

Version / remarks:

Draize (1959). Dermal toxicity. Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Texas State
Department of Health, Austin, Texas

Principles of method if other than guideline:

- Principle of test: To determine by dermal contact the primary or cumulative irritation and/or sensitisation potential of a test material
- Short description of test conditions: Fifty-one male / female human participants aged from 17 - 62 years completed the evaluation. Eight materials were examined, including PPG-2 myristyl ether propionate. Approximately 0.15 ml of each material was applied to a 1.5 x 2 inch portion of gauze, which were then applied to the upper back between the scapulae. The procedure was followed three times per week every other day (Monday, Wednesday, and Friday) for a total of ten applications. Each site was marked to ensure continuity of patch applications. After a 24-hour period, participants were instructed to remove the induction patches and evaluation of each site for erythema and/or edema was made immediately prior to re-application. Rest periods consisted of 24 hours on a Tuesday and Thursday following removal of the gauze patches and 48 hours following removal on Saturday. After a 14-day rest period from the tenth application, challenge patches were applied to the original sites and to virgin sites on the volar forearms. Each area was evaluated at 24 and 48 hours after application and the response after challenge compared to any response observed after the early induction patches
- Parameters analysed / observed: Erytheme, edema, and vosiculation and ulceration
- Status of validation / standardisation: No standardised test guideline is available. The HRIPT test has not undergone a formal validation process

GLP compliance:

no

Species:

other: Human (male / female)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Selection criteria: Willingness to cooperate; absence of any visible skin disease that might be confused with skin reaction from the test material; dependability and intelligence in following directions; and reading, understanding, and signing an informed consent contract
- Age at study initiation: 18 - 65 years

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.15 ml of each test material

Duration of treatment / exposure:

Ten applications of treated patches consisting of a 24-hour exposure period. Applications took place on a Monday, Wednesday, and Friday, with a 24-hour rest period following Tuesday and Thursday removal, and a 48-hour rest period following Saturday removal. At the conclusion of a 14-day rest period following the tenth application, challenge patches were applied and evaluated at 24 and 48 hours after application.

Observation period:

Examination of the skin sites was made 24 hours after the removal of the Monday and Wednesday patches and at 48 hours following the removal of the Friday treatment patch (i.e. immediately before re-application).

Number of animals:

Fifty-one

Details on study design:

TEST SITE
- Area of exposure: Upper back between the scapulae
- Coverage: 1.5 x 2 inch gauze portion
- Type of wrap: Gauze portion of a Coverlet adhesive dressing

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: Patches were removed after 24-hours by the participants

OBSERVATION TIME POINTS: Ten observation points that occurred immediately prior to reapplication (i.e. 24 or 48 hours after end-exposure). After a 14-day rest, tested areas at the original and virgin sites were evaluated at 24 and 48 hours after challenge patch application

SCORING SYSTEM: No visible reaction - 0; mild erythema - 1+; well defined erythema - 2+; erythema and edema - 3+; erythema and edema with vosiculation and ulceration - 4+

Irritation parameter:

other: Erythema / edema

Basis:

other: mean

Time point:

other: All

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Primary and cumulative dermal exposure to PPG-2 myristyl ether propionate did not result in erythema, edema, and/or vosiculation and ulceration over the study period. No visible reaction was observed.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study PPG-2 myristyl ether propionate did not exhibit any potential for dermal irritation and/or sensitisation in human participants and, therefore, it does not meet criteria for classification according to CLP Regulation (EC) No. 1272/2008.

Executive summary:

PPG-2 myristyl ether propionate was applied to the upper back of fifty-one human participants (male / female) between the scapulae in order to determine its irritation and sensitisation potential. A guideline was not specified in the experimental report; however, the test procedure appears to be similar to that outlined in the Human Repeated Insult Patch Test (HRIPT) by Draize et al. (1944) and Draize (1959). A concentration of 0.15 ml PPG-2 myristyl ether propionate was applied to the gauze portion (1.5 inch x 2 inch) of Coverlet adhesive dressings and applied to the skin site to form an occlusive covering. The procedure was repeated three times per week on alternating days (Monday, Wednesday, and Friday) for a total of ten applications and removed by the participants after a 24-hour exposure time. A rest period of 24 hours (Tuesday and Thursday) or 48 hours (Saturday / Sunday) occurred between the application points. Examination for erythema, edema, and/or vesiculation and ulceration was made immediately prior to re-application and an appropriate grading score assigned from 0 - 4 based on the severity of any skin lesions. Following the tenth application, a rest period consisting of 14 days was permitted. Challenge patches were applied to the original back and virgin forearm skin sites thereafter and observed at 24 and 48 hours. Across all participants during the study period, no visible reaction was observed in the ten induction exposures, nor in the later original and virgin site skin test. It was concluded that PPG-2 myristyl ether propionate is not a dermal irritant or sensitiser and that it does not require classification (CLP Regulation (EC) No. 1272/2008).

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 14, 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

other: Draize test

Version / remarks:

Draize, J. H., Woodward, G. and Calvery, H. O (1944). Methods for the Study of Irritation and Toxicity of Substances Applied Topically to the Skin and Mucous Membranes. Journal of Pharmacology and Experimental Therapeutics, 82 (3), 377-390

Principles of method if other than guideline:

- Principle of test: Primary dermal irritation study in rabbits
- Short description of test conditions: The test method was essentially that of Draize et al (1944). Six albino New Zealand rabbits (half male and half female) were selected, each abraded and non-abraded, and treated with a single dose of 0.5 ml PPG-2 myristyl ether propionate under an occluded patch (1 x 1 inch gauze covered by adhesive tape) on skin that had been clipped of hair. The abrasions were longitudinal epidermal incisions sufficiently deep to penetrate the stratum corneum, but not so deep as to destroy the integrity of the derma. Following application of the test material the entire trunk of each animal was covered with an impermeable occlusive wrapping and the animals were immobilised. Observations for potential dermal irritation were made 24 and 72 hours after patch removal by examining each site individually and scoring separately for erythema and/or edema
- Parameters analysed / observed: Erythema and edema formation (score 0 - 4) and edema formation (score 0 - 4)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Summit View Farm, Belvidere, New Jersey (conditioned prior to use)
- Diet: Ad libitum with Wayne animal feed
- Water: Ad libitum

Type of coverage:

occlusive

Preparation of test site:

other: Clipped and abraded / non-abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml single application

Duration of treatment / exposure:

24 hour exposure period

Observation period:

Examination of skin sites 24 and 72 hours after patch removal

Number of animals:

Six rabbits (three male and three female)

Details on study design:

TEST SITE
- Type of wrap if used: Occlusive patch consisting of 1 inch x 1 inch gauze, covered by adhesive tape. The entire trunk of each animal was subsequently covered with an impermeable occlusive wrapping

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: Material removed after 24 hours

OBSERVATION TIME POINTS: 24 and 72 hours

SCORING SYSTEM:
- Erythema and edema formation: Very slight erythema (barely perceptible) - 1; well-defined erythema - 2; moderate to severe erythema - 3; severe erythema (beet redness) to slight eschar formation (injuries in depth) - 4
- Edema formation: Very slight erythema (barely perceptible) - 1; slight edema (edges of area well-defined by definite raising) - 2; moderate edema (area raised approximately 1 mm) - 3; severe edema (raised more than 1 mm and extending beyond area of exposure) - 4
- Total possible: Erythema score = 4; edema score = 4; primary irritation score = 8

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24/72 h

Score:

0.9

Max. score:

8

Remarks on result:

probability of weak irritation

Remarks:

rarely irritating to people - no warning required

Irritant / corrosive response data:

Very slight erythema (barely perceptible) was noted in rabbit 2, 5, and 6 at 72 hours post-patch removal, with rabbit 4 exhibiting signs of well-defined erythema. Only rabbit 4 displayed signs of edema by 72 hours, specifically, very slight edema (barely perceptible). A combined average across the study for primary skin irritation was calculated to give 3.6 (primary irritation index: 0.9). Overall, PPG-2 myristyl ether propionate was considered not to be a dermal irritant to rabbits.

Interpretation of results:

GHS criteria not met

Conclusions:

Following an in vivo primary dermal irritation study in New Zealand albino rabbits, it was concluded that PPG-2 myristyl ether propionate was not a dermal irritant under the conditions of this test.

Executive summary:

An in vivo primary dermal irritation study was undertaken to determine whether PPG-2 myristyl ether propionate possessed skin irritation potential using a protocol similar / equivalent to that of Draize et al. (1944) (Methods for the Study of Irritation and Toxicity of Substances Applied Topically to the Skin and Mucous Membranes). 0.5 ml (0.5 g) was applied to clipped areas of intact and abraded skin under occlusive patches that consisted of 1 inch x 1 inch gauze covered by adhesive tape. The wrapping material and test item were removed 24 hours post-application. Each skin site was individually examined at 24 and 72 hours and assigned a standard grading score related to the severity of any erythema and/or edema. Very slight erythema (barely perceptible) was noted in three rabbits at 72 hours post-patch removal, with an additional rabbit exhibiting signs of well-defined erythema and very slight edema by 72 hours (barely perceptible). An average of all erythema / edema gradings was obtained to give an overall skin irritation index of 0.9. PPG-2 myristyl ether propionate was determined to have slight irritation potential but rarely irritating to humans. Classification for hazard labelling is not required (CLP Regulation (EC) No. 1272/2008).

Reference 3

Endpoint:

skin corrosion: 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:

no adverse effect observed (not 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:

July 14, 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

other: Eye Irritation Test

Version / remarks:

Method used by J. H. Draize in Appraisal of the Safety of Chemicals in Food, Drugs, and Cosmetics, compiled by the staff of the Division of Pharmacology, Food, and Drug Administration - Department of Health, Education, and Welfare

Qualifier:

according to guideline

Guideline:

other: Scale of Weighted Scores for Grading the Severity of Ocular Lesions

Version / remarks:

Standard score system from Draize, J. H., Woodward, G. and Calvery, H. O (1944). Methods for the Study of Irritation and Toxicity of Substances Applied Topically to the Skin and Mucous Membranes. Journal of Pharmacology and Experimental Therapeutics, 82 (3), 377-390

Principles of method if other than guideline:

- Principle of test: To determine the extent of ocular irritation hazard from a particular substance in rabbits according to the Draize Rabbit Eye Test
- Short description of test conditions: Six healthy New Zealand rabbits of mixed sex that weighed 1.8 - 2.4 kg were used to determine the potential of PPG-2 myristyl ether propionate to induce irritation to eye mucosa. A single administration of 0.1 ml was applied to the right eye (the left served as a control) and the eyes were not washed for 24 hours. Observations took place on day 1, 2, and 3 and were extended up to 7 days where necessary. During this time, observations of injuries were made on the cornea, iris, and the bulbar and palpebral conjunctive. Readings were facilitated by hand-held lenses. A standard score system from 1 – 4 was used to quantify the severity of lesions (Draize et al. 1944)
- Parameters analysed / observed: Injury to the cornea and iris. These account for approximately 80 % of the total score because of their vital role in vision

GLP compliance:

no

Species:

rabbit

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Summit View Farm, Belvidere, New Jersey (conditioned prior to use)
- Weight at study initiation: 1.8 - 2.4 kg
- Diet: Ad libitum with Wayne animal feed
- Water: Ad libitum

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.1 ml instilled in the right eye

Duration of treatment / exposure:

The treated eyes of all rabbits remained unwashed for 24 hours

Observation period (in vivo):

Examinations were made on day 1, 2, and 3, and up to 7 days if required

Number of animals or in vitro replicates:

Six New Zealand rabbits of mixed sex

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Yes
- Time after start of exposure: Treated eyes were washed after 24 hours

SCORING SYSTEM:
Cornea
- Cornea opacity (A) based on degree of density (area which is dense is taken for reading): Scattered or diffuse area, details of iris clearly visible - 1; easily discernible translucent areas, details of iris slightly obscured - 2; opalescent areas, no details of iris visible, size of pupil barely discernible - 3; opaque, iris invisible - 4
- Area of cornea involved (B): One-quarter (or less), but not zero - 1; greater than one-quarter, but less than one-half - 2; greater than one-half, but less than three-quarters - 3; greater than three-quarters, up to whole area - 4
- Score = A x B x 5, total maximum of 80

Iris
- Values (A), folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combinations of any thereof), iris still reacting to light: Sluggish reaction is positive - 1; no reaction to light haemorrhage, gross destruction (any or all of these) - 2
- Score = A x 5, total maximum of 10

Conjunctive
- Redness (A), refers to palpebral conjunctivae only: Vessels definitely injected above normal - 1; more diffuse, crimson red, individual vessels not easily discernible - 2; diffuse beefy red - 3
- Chemosis (B): Any swelling above normal (including nictitating membrane) - 1; obvious swelling with partial eversion of the lids - 2; swelling with lids about half-closed - 3; swelling with lids about half-closed to completely closed - 4
- Discharge (C): Any amount different from normal (does not include small amount observed in inner canthus of normal animals) - 1; discharge with moistening of the lids and hairs just adjacent to the lids - 2; discharge with moistening of the lids and hairs and considerable area around eye - 3
- Score equals (A + B + C) x 2, total maximum of 20

Note: The maximum total score is the sum of all scores obtained for the cornea, iris, and conjunctivae

TOOL USED TO ASSESS SCORE: Hand-held lenses

Irritation parameter:

other: Corneal opacity (A) plus area of cornea involved (B) score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

80

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Remarks:

Values (A)

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

10

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness (A), chemosis (B) and discharge (C)

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

20

Remarks on result:

no indication of irritation

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

110

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No sign of primary eye irritation was observed in the cornea, iris, or conjunctivae following application of PPG-2 myristyl ether propionate. This resulted in grading scores of 0 across all inspected ocular tissues, in all rabbits between day 0 and 3. Examination past this time point was not necessary.

Interpretation of results:

GHS criteria not met

Conclusions:

Following 24-hour exposure to PPG-2 myristyl ether propionate, the registered substance was determined not to be an ocular irritant under the conditions of this test.

Executive summary:

A study was performed using a modified version of the Rabbit Eye Test by J. H. Draize from the Appraisal of the Safety of Chemicals in Food, Drugs, and Cosmetics in conjunction with a standard score system to permit weighted grading of the severity of any ocular lesion (Draize et al. 1944). In this system, injuries to the cornea and iris account for approximately 80 % of the total score due to their vital role in vision. The test aimed to determine the eye irritation potential of PPG-2 myristyl ether propionate in New Zealand rabbits of mixed sex following a 0.1 ml single administration to the right eye mucosa. The treated eye was left unwashed for a 24-hour exposure period. The left eye served as a control. Observations of injuries to the cornea, iris, and bulbar and palpebral conjunctivae were scheduled on day 1, 2, and 3, up until day 7 where necessary. Accurate grading was facilitated by hand-held lenses. The maximum total score was the sum of all scores obtained for the cornea, iris, and conjunctivae. On day 1, 2, and 3, ocular irritation was not observed in any rabbit, resulting in a total score of 0 of 110. Examination of the treated eye past day 3 was not necessary. It can be concluded that PPG-2 myristyl ether propionate is not an ocular irritant based on the conditions of this test and classification is not required (CLP Regulation (EC) No. 1272/2008).

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

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

The endpoint conclusion obtained for skin irritation is determined to be suitable for regulatory purpose. The study detailed in record .001 was completed prior to Good Laboratory Practise (GLP) regulations of 1979 (21 CFR Part 58) but followed a protocol that is considered to be similar / equivalent to the Human Repeated Insult Patch Test (HRIPT) by Draize et al. (1944) and Draize (1959). Given that the procedure was published by The Journal of Pharmacology and Experimental Therapeutics and The Association of Food and Drug Officials of the United States, Department of Health it can be considered to be a national standard method. The restrictions of the study are acceptable and, therefore, a Klimisch score of 2 (reliable with restrictions) has been assigned. The conclusion obtained in record .002 has been assigned a reliability score of 2 as the test procedure, similar / equivalent to Draize et al. (1944), is in accordance with national standard methods with acceptable restrictions.

The eye irritation endpoint was derived from a key study that used a modified version of the Rabbit Eye Test by J. H. Draize, published by a reputable organisation, the Division of Pharmacology, Food, and Drug Administration - Department of Health, Education, and Welfare. The grading system followed to assess lesion severity was published by the Journal of Pharmacology and Experimental Therapeutics (Draize et al. 1944). The study was not GLP compliant, however, it was conducted prior to the introduction of the regulation. The restrictions of the endpoint are deemed to be acceptable and a Klimisch score of 2 (reliable with restrictions) has been recommended.