Hexadecyl palmitate

Endpoint summary

Description of key information

Skin, rabbit (similar to OECD 404): not irritating

Skin, rabbit (read across, OECD 404): not irritating

Eye, rabbit (read across, OECD 405): not irritating

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:

weight of evidence

Study period:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

yes

Remarks:

Limited documentation

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted in 2015

Deviations:

yes

Remarks:

Limited information on test substance, methods, no reading at 48 hours

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

other:

Remarks:

intact and abraded skin

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 500 mg of the product
- Concentration: pur product

Duration of treatment / exposure:

24 h

Observation period:

72 h
Reading time points: 24 and 72 h

Number of animals:

6 male animals

Details on study design:

OBSERVATION TIME POINTS: 24 h and 72 h

SCORING SYSTEM:
- Method according to OECD GL 404 (Draize scoring system)

Irritation parameter:

erythema score

Remarks:

intact skin and abraded skin

Basis:

animal #1

Time point:

other: mean after 24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other:

Remarks:

for calculating the mean score, the 48 h values were assumed to be the same as for 24 h

Irritation parameter:

erythema score

Remarks:

intact and abraded skin

Basis:

mean

Remarks:

of 5 animals

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

not applicable

Remarks on result:

other:

Remarks:

for calculating the mean score, the 48 h values were assumed to be the same as for 24 h

Irritation parameter:

edema score

Remarks:

intact skin and abraded skin

Basis:

mean

Remarks:

of 6 animals

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

not applicable

Remarks on result:

other:

Remarks:

for calculating the mean score, the 48 h values were assumed to be the same as for 24 h

	24 hours				72 hours
	Erythema		Oedema		Erythema		Oedema
Animal	intact skin	incised skin	intact skin	incised skin	intact skin	incised skin	intact skin	incised skin
#1	0	0	0	0	0	0	0	0
#2	0	0	0	0	0	0	0	0
#3	0	0	0	0	0	0	0	0
#4	1	1	0	0	0	0	0	0
#5	0	0	0	0	0	0	0	0
#6	0	0	0	0	0	0	0	0

Method similar to OECD 404

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

26 -29 May 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The analytical purity of the test substance was not specified.

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ESD (Chatillon sur Chalaronne, France)
- Weight at study initiation: 2-2.5 kg
- Housing: animals were housed individually in stainless steel cages with a wiremesh floor
- Diet: Food ref. 110-10 (U.A.R., Epinay sur Orge, France), ad libitum
- Water: filtered tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 30-80
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 26 May 1999 To: 29 May 1999

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: not required, untreated sites of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

3 days
Reading time points: 1, 24, 48 and 72 h

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: a gauze patch covering the test site was held in place by micropore tape; the trunk of the animals was wrapped in an elastic gauze band and semiocclusive, adhesive tape. Access to the test site was restricted with a plastified aerated wrapping fixed to the trunk of the animals with velcro tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the remnants of the test substance were removed with distilled water or, if necessary, a suitable solvent
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritation effects were observed at any time point in any animal.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

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:

weight of evidence

Study period:

26 - 31 May 1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The analytical purity of the test substance was not specified.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: ESD (Chatillon sur Chalaronne, France)
- Weight at study initiation: 2-2.5 kg
- Housing: animals were housed individually in high impact polystyrene cages with a mesh floor
- Diet: Food ref. 112 (U.A.R., Epinay sur Orge, France)
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 30-80
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 26 May 1999 To: 31 May 1999

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Single application without washing

Observation period (in vivo):

7 days
Reading time points: 1, 24, 48 and 72 h, and 7 days

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eye was not washed

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: After instilling 2% fluorescein into the eyes, any damage was assessed with a UV-lamp

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2, #3

Time point:

other: mean after 24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

At the 1-hour reading time point, 3/3 rabbits had slight-moderate conjunctivae (scores 1, 1, 2) and 2/3 slight chemosis (scores 0, 1, 1). The chemosis had cleared by the 24-hour reading time point, while 3/3 animals still had slight conjunctivae (scores 1, 1, 1). All eye irritation effects were fully reversible within 48 hours.

Table 1: Eye irritation score

Rabbit #	Time [h]	conjunctivae		iris	cornea
		redness	chemosis
1	1	1	0	0	0
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.0	0.0	0.0
2	1	2	1	0	0
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.0	0.0	0.0
3	1	1	1	0	0
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.0	0.0	0.0

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

23 - 26 Feb 1998

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:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Broekman Institute, Someren, the Netherlands
- Age at study initiation: 8 weeks
- Weight at study initiation: 1.49-1.58 kg
- Housing: individually housed in labelled cages with perforated floors (Scanbur, Denmark)
- Diet: standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, the Netherlands), approximately 100 g/day. Hay (BMI, Helmond, the Netherlands) was provided once a week.
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 Feb 1998 To: 26 Feb 1998

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

Single application without washing

Observation period (in vivo):

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the eye was not washed after application

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: during the 24-hour reading time point, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal and the extent of corneal epithelial damage was assessed using a UV-light.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

iris score

Basis:

other: each of 3 animals

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean after 24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of animals #2 and #3

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

At the 1-hour reading time point 3/3 rabbits had slight conjunctivae (score 1, 1, 1), which was still present in 1/3 rabbits at the 24-hour reading time point. The effect had cleared completely within 48 hours. No other eye irritation effects were observed in any rabbit at any time point (see Table 1).

Other effects:

There was no mortality, and no clinical signs were observed during the study period.

Table 1: Eye irritation scores

Rabbit #	Time [h]	conjunctivae		iris	cornea
		redness	swelling
1	1	1 (AB)	0	0	0
	24	1 (A)	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.0	0.0	0.0
2	1	1 (ABC)	0	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.00	0.0	0.0	0.0
3	1	1 (AB)	0	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.00	0.0	0.0	0.0

 

	Time [h]	conjunctivae		iris	cornea
		redness	swelling
average score	1	1.00	0.00	0.00	0.00
	24	0.33	0.00	0.00	0.00
	48	0.00	0.00	0.00	0.00
	72	0.00	0.00	0.00	0.00
	24+48+72	0.11	0.00	0.00	0.00

A = eyelids

B = nictating membrane

C = sclera

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for read-across

There are no adequate study data on the skin and eye irritation effects of Hexadecyl palmitate (CAS 540-10-3). The assessment was therefore based on data without detailed documentation, secondary literature and studies conducted with analogue substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Skin irritation

 

CAS 540-10-3

A skin irritation study was performed according to OECD guideline 404 with Hexadecyl palmitate (WoE, 1985). The report contained limited documentation. Six rabbits were exposed for 24 hours to 500 mg of the unchanged solid test substance under occlusive conditions. Readings were done at 24 and 72 hours using the Draize scoring system.

Slight erythema of score 1 was noted only in one out of 6 rabbits at the 24-hour reading time point, which was fully reversible within 72 hours. No oedema was reported in any of the animals at any reading time point. The individual mean erythema and oedema scores over 24/48/72-hour readings were calculated using the value recorded at the 24-hour reading time point instead of the missing 48-hour value as a worst case approach. The individual mean erythema scores over 24/48/72 hours were 0.66, 0, 0, 0, 0 and 0. The substance was not considered to cause skin irritation.

 

As referenced in the publication “Final Report on the Safety Assessment of Octyl Palmitate, Cetyl Palmitate and Isopropyl Palmitate”, International Journal of Toxicology, Jan 1, 1990, the skin irritation potential of Hexadecyl palmitate (named as Cetyl palmitate) was summarised in 4 separate in vivo studies. In each study, samples of diluted or undiluted Hexadecyl palmitate were applied under occlusive patches on clipped areas of the intact and abraded skin of six albino rabbits and occluded for 24 hours. Skin irritation reactions were evaluated at 24 and 72 hours.

In the first study, 0.5 mL of a 5% w/w dispersion of Hexadecyl palmitate in mineral oil produced a Primary Irritation Index (PII) of 0.38. The mean score was 0.75 at 24 hours; all scores were 0.0 at 72 hours. In the second study, 1.0 mL of a 50% dispersion in distilled water was used, giving an effective dosage of 500 mg of Hexadecyl palmitate. All reaction scores were 0.0. In the third study, 0.5 g of Hexadecyl palmitate moistened with saline produced a PII of 0.17. In the fourth study, Hexadecyl palmitate was melted and used as a liquid at 100% concentration. A dose of 0.5 ml produced a PII of 0.4. The mean score at 24 hours was 0.8; all scores were 0.0 at 72 hours. In these fourin vivostudies, Hexadecyl palmitate (named Cetyl palmitate) showed no or only mild skin irritating potential. Due to the limited documentation and lack of individual scores, this data cannot be used for classification purposes.

 

CAS 72576-80-8

A skin irritation study equivalent to OECD guideline 404 (WoE, 1999) was performed with Isooctadecyl palmitate (CAS 72576-80-8). 0.5 mL of the liquid test substance was applied to the shaved skin of 3 male rabbits for 4 hours of exposure under semi-occlusive conditions. Skin irritation readings were done at 1, 24, 48, and 72 hours. No erythema or oedema was found at the 24-, 48-, and 72-hour reading time point . No indication of irritation to skin was found for the test substance. The individual mean erythema and oedema scores over 24/48/72-hours were 0.0 for each rabbit.

 

Eye irritation

CAS 540-10-3

Three separate in vivo eye irritation studies were summarised in secondary literature (Cosmetic Ingredient Review, 1982). The Draize eye irritation technique was used to evaluate the eye irritation potential ofHexadecyl palmitate (Cetyl palmitate). In each, 0.1 ml or 0.1 g of the test material was instilled into the conjunctival sac of one eye in each of six rabbits. The treated eyes were examined and graded on the Draize eye irritation scale at 24, 48, and 72 hours. In one study, the Draize Ocular Irritation Index for a 5% w/w dispersion ofHexadecyl palmitatein mineral oil was 0.0 for all days. The Draize scores for 100%Hexadecyl palmitatein another study were 0.3 on the first day and 0.0 thereafter. In the third study,Hexadecyl palmitatedelivered as a white powder received scores of 2.3 on the first day, 0.7 on the second day, and 0.3 on the third day. The Ocular Irritation Indices for undilutedHexadecyl palmitatein the fourth study were 6.7 on the first day, 2.2 on the second day, and 0.0 on the third day. The ocular irritation indices reported in the secondary literature did not provide details on primary irritation scores and therefore the referenced studies could not be used for classification.

 

CAS 72576-80-8

An eye irritation GLP study was performed with Isooctadecyl palmitate (CAS 72576-80-8) according to OECD guideline 405 (WoE, 1999). 0.1 mL of the unchanged test substance was instilled into one eye of each of 3 male New Zealand White rabbits. The animals were observed for 7 days and scoring according to Draize was performed 1, 24, 48 and 72 hours, and 7 days after application. The eyes were not rinsed. At the 1-hour reading time point, 3/3 rabbits had slight-moderate conjunctivae (scores 1, 1, 2) and 2/3 slight chemosis (scores 0, 1, 1). The chemosis had cleared by the 24-hour reading time point, while 3/3 animals still had slight conjunctivae (scores 1, 1, 1). All eye irritation effects were fully reversible within 48 hours. The individual mean cornea opacity, iris, and chemosis scores over 24/48/72 hours were 0.0 for each rabbit. The individual mean conjunctivae scores over 24/48/72 hours were 0.33, 0.33 and 0.33 . The test substance did not cause eye irritation under the conditions of the study.

CAS 93803-87-3

2-octyldodecyl isooctadecanoate (CA 93803-87-3) was examined for its eye irritation potential in a GLP study performed according to OECD guideline 405 (WoE, 1998). 0.1 mL of undiluted test liquid test substance was instilled into one eye of each of 3 rabbits. The animals were observed for 72 hours and scoring according to Draize was performed 1, 24, 48, and 72 hours after application. At the 1-hour reading time point 3/3 rabbits had slight conjunctivae (score 1, 1, 1), which was still present in 1/3 rabbits at the 24-hour reading time point. The effect had cleared completely within 48 hours. No other eye irritation effects were observed in any rabbit at any time point. The individual mean cornea opacity, iris, and chemosis scores over 24/48/72-hour readings were 0.0 for each rabbit. The individual mean conjunctivae scores over 24/48/72-hour readings were 0.33, 0 and 0. The test substance did not cause eye irritation under the conditions of the study.

 

Overall conclusion for skin and eye irritation

The available data for the target and source substances indicate no or only mild skin and eye irritation potential. No skin or eye irritation potential is expected for the target substance Hexadecyl palmitate (CAS 540-10-3).

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Hexadecyl palmitate (CAS 540-10-3), data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

 

The available data on skin and eye irritation do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.