Glycerides, palm-oil mono- and di-, hydrogenated

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GCP-compliant, acceptable and well documented study report which meets basic scientific principles. Lack of details on test material

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Study type:

study with volunteers

Endpoint addressed:

skin irritation / corrosion

Principles of method if other than guideline:

Duhring-Kammer-Test (occlusive, epicutaneous patch test) in human volunteers

GLP compliance:

no

Remarks:

GCP-compliant

Test material

Test material information

Constituent 1

Reference substance name:

Glycerides, palm-oil mono- and di-, hydrogenated

EC Number:

267-057-3

EC Name:

Glycerides, palm-oil mono- and di-, hydrogenated

Cas Number:

67784-87-6

Molecular formula:

C19-39H38-76O4-5

IUPAC Name:

1,3-dihydroxypropan-2-yl hexadecanoate; 1,3-dihydroxypropan-2-yl octadecanoate; 1-hydroxy-3-(octadecanoyloxy)propan-2-yl octadecanoate; 2-(hexadecanoyloxy)-3-hydroxypropyl octadecanoate

Details on test material:

- Name of test material (as cited in study report): only trade name given
- Analytical purity: no data
- Lot/batch No.: MD01785037

Method

Type of population:

general

Subjects:

- Number of subjects exposed: 20
- Sex: male and female
- Age: 21-54 years (mean value: 38.7 years)
- Other: 15 test subjects had normal skin, 5 test subjects had sensitive skin.

Ethical approval:

not specified

Route of exposure:

dermal

Reason of exposure:

intentional

Exposure assessment:

measured

Details on exposure:

TEST SYSTEM

TEST PATCH
- Type of patch: Large-Finn-Chambers (12 mm in diameter) on Scanpor(R)-Patches
- Type of coverage: occlusive

AMOUNT / CONCENTRATION APPLIED
- Amount of test material applied: 70 µL/patch
- Concentration: 20%
- Preparation: The test material was prepared in 60% cosmetic alcohol. The test material was first mixed with the water fraction by stirring and slightly heating. The alcohol fraction was then added to the mixture yielding an emulsion.

VEHICLE
- Vehicle: cosmetic alcohol (98.8%, denaturated) with 0.5% DEP
- Concentration: 60% in demineralized water

CONTROLS
- Reference substances: demineralized water, physiological saline, cosmetic alcohol, 0.5% SDS, 1.0% Texapon N28

DURATION OF TREATMENT / EXPOSURE: 24 h

OBSERVATION PERIOD: 72 h (reading time points: 6, 24, 48 and 72 h)

TEST SITE
- Area of exposure: The occlusive test patches were applied on the back of the test subjects.

Examinations:

- Skin parameters examined: erythema, edema, scaling and scissures
- Scoring system: The following scoring scale was used to evaluate the degree of effects in the skin parameters examined:
0: no reaction
0.5: very slight reaction
1: slight reaction
2: moderate reaction
3: strong reaction
4: very strong reaction
-1: no response

EVALUATION
- Frequency of skin reactions: The frequency of occurrence of skin reactions and their corresponding degree were determined for all 20 subjects over all 4 reading time points and expressed as the incidence of a skin reaction of a given score out of all 80 individual readings:
Frequency = (incidence n of score m)/80
- Irritation indices
Sum Erythema Index: The sum erythema index was calculated as the overall sum of incidence of erythema multiplied by the assigned score(s) and divided by the number of subjects (20):
Sum Erythema Index = [SUM(erythema incidence n(i) x erythema score m(i))]/20
Sum Irritation Index: The sum irritation index was calculated in analogy to the sum erythema index by additionally taking into account the incidence and corresponding scores of the remaining parameters examined:
Sum Irritation Index = [SUM(skin reaction incidence n(i) x skin reaction score m(i))]/20
- Comparison with reference substances: The results obtained for the test material were compared with those for the (positive) reference substances (0.5% SDS, 1.0% Texapon N28) by calculating the ratio of the sum erythema and irritation indices for the test material and the reference substances, respectively, and expressed as per cent effect of the corresponding reference substance:
[Sum Erythema or Irritation Index (test material) / Sum Erythema or Irritation Index (reference substance)] x 100

STATISTICS
Differences in the frequency and degree of skin reactions between the test material and the (negative) reference substance cosmetic alcohol were determined by means of the two-tailed Wilcoxon rank-sum test. The statistical significance of rank-sum differences was assessed by comparison with tabulated literature values (Wilcoxon-Wilcox: Some rapid approximate statistical procedures, Lederle Laboratories, 1964, Tab. 6, p. 39, 41):
Rank-sum difference (statistical significance): 14.9 (95%*) and 18.5 (99%**)

Results and discussion

Clinical signs:

No clinical signs were reported.

Results of examinations:

FREQUENCY OF SKIN REACTIONS
Test Material:
- No. of subjects without skin reactions: 14/20
- Erythema: Slight erythema was observed at 1/80 readings.
- Edema: Not observed.
- Scaling: Slight, moderate and strong scaling was observed at 5/80, 3/80 and 1/80 readings, respectively.
- Scissures: Not observed.

Demineralised water (negative reference substance):
- No. of subjects without skin reactions: 19/20
- Erythema: Not observed.
- Edema: Not observed.
- Scaling: Slight scaling was observed at 1/80 readings.
- Scissures: Not observed.

Cosmetic alcohol (negative reference substance):
- No. of subjects without skin reactions: 17/20
- Erythema: Slight erythema was observed at 1/80 readings.
- Edema: Not observed.
- Scaling: Slight and moderate scaling was observed at 3/80 and 1/80 readings, respectively.
- Scissures: Not observed.

Physiological saline (negative reference substance):
- No. of subjects without skin reactions: 19/20
- Erythema: Not observed.
- Edema: Not observed.
- Scaling: Slight scaling was observed at 1/80 readings.
- Scissures: Not observed.

0.5% SDS (positive reference substance):
- No. of subjects without skin reactions: 2/20
- Erythema: Slight, moderate and strong erythema was observed at 24/80, 14/80 and 2/80 readings, respectively.
- Edema: Slight and moderate edema was observed at 5/80 and 1/80 readings, respectively.
- Scaling: Slight, moderate, strong and very strong scaling was observed at 13/80, 20/80, 10/80 and 2/80 readings, respectively.
- Scissures: Slight, moderate and strong scissures were observed at 4/80, 4/80 and 1/80 readings, respectively.

1.0% Texapon N28 (positive reference substance):
- No. of subjects without skin reactions: 5/20
- Erythema: Slight erythema was observed at 16/80 readings.
- Edema: Not observed.
- Scaling: Slight, moderate and strong scaling was observed at 17/80, 4/80 and 1/80 readings, respectively.
- Scissures: Not observed.

IRRITATION INDICES
The Sum Erythema and Irritation Indices for the test material were 0.05 and 0.75, and comparable to those obtained for the negative reference substance cosmetic alcohol (0.05, 0.30). Corresponding values for the negative reference substances demineralised water (0.00, 0.05) and physiological saline (0.00, 0.05) were lower.
The Sum Erythema and Irritation Indices for the positive references substances 0.5% SDS (2.90, 8.10) and 1.0% Texapon N28 (0.80, 2.20) were higher as expected.

COMPARISON OF RESULTS BETWEEN TEST MATERIAL AND (POSITIVE) REFERENCE SUBSTANCES (Table 3)
The per cent erythema effect for the test material compared with the positive reference substances 0.5% SDS and 1.0% Texapon N28 was 1.7 and 6.2%, respectively.
The overall per cent skin reaction for the test material compared with the positive reference substances 0.5% SDS and 1.0% Texapon N28 was 9.3 and 34.1%, respectively.

RANK-SUM DIFFERENCES AND STATISTICAL SIGNIFICANCE (Table 4)
No statistically significant rank-sum differences were observed between the test material and the reference substance cosmetic alcohol for any of the skin parameters examined.

OVERALL EVALUATION
Under the test conditions of the study, the skin compatibility of the test material (20% AS in 60% cosmetic alcohol) was not significantly different in comparison with pure cosmetic alcohol. Thus, the test material shows a good skin compatibility.

Any other information on results incl. tables

Table 1. Frequency of skin reactions and degree (scores).

Substance	Subjects without reactions	Erythema						Edema						Scaling						Scissures
		0.5	1	2	3	4	0	0.5	1	2	3	4	0	0.5	1	2	3	4	0	0.5	1	2	3	0
Test material	14/20	0	1	0	0	0	79	0	0	0	0	0	80	0	5	3	1	0	71	0	0	0	0	80
Demineralised water	19/20	0	0	0	0	0	80	0	0	0	0	0	80	0	1	0	0	0	79	0	0	0	0	80
Cosmetic alcohol	17/20	0	1	0	0	0	79	0	0	0	0	0	80	0	3	1	0	0	76	0	0	0	0	80
Physiological saline	19/20	0	0	0	0	0	80	0	0	0	0	0	80	0	1	0	0	0	79	0	0	0	0	80
0.5% SDS	2/20	0	24	14	2	0	40	0	5	1	0	0	74	0	13	20	10	2	35	0	4	4	1	75
1.0% Texapon N28	5/20	0	16	0	0	0	64	0	0	0	0	0	80	0	17	4	1	0	58	0	0	0	0	80

 

 

Table 2. Irritation indices.

Substance	Sum Erythema Index	Sum Irritation Index (erythema + edema + scaling + scissures)
Test material	0.05	0.75
Demineralised water	0.00	0.05
Cosmetic alcohol	0.05	0.30
Physiological saline	0.00	0.05
0.5% SDS	1.90	8.10
1.0% Texapon N28	0.80	2.20

 

 

Table 3. Comparison with (positive) reference substances.

Substance	Per cent effect compared with reference substance
	Erythema		Erythema + Edema + Scaling + Scissures
	0.5% SDS	1.0% Texapon N28	0.5% SDS	1.0% Texapon N28
Test material	1.7%	6.2%	9.3%	34.1%

 

 

Table 4. Rank-sum differences between test material and (negative) reference substance cosmetic alcohol and statistical significance (Wilcoxon rank-sum test).

Skin reaction	Rank-sum difference	Statistical significance (two-tailed)
Erythema	0.0	no
Edema	identical	-
Scaling	6.5	no
Scissures	identical	-

Applicant's summary and conclusion

Conclusions:

Not skin irritating (at 20% AS in 60% cosmetic alcohol)