Registration Dossier

Toxicological information

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
Study period:
January to February 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Type of study / information:
Type of method: in vivo study with volunteers
Endpoint addressed:
skin irritation / corrosion
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Human 10-day occlusion test: according to the method of A. M. Kligman and W. Wooding: A method for the measurement and evaluation of irritants on human skin; J. Invest. Derm. 49: 78-94, 1967.
3-day chamber scarification test: according to the method of Frosch, P.J. and A.M. Kligman: The chamber-scarification test of irritancy. Contact Dermatitis 2: 314-324, 1976
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Ethical approval:
not specified
Details on study design:
Test on intact skin:
The ten-day occlusive patch test method was used (A.M. Kligman and W. Wooding: A method for the measurement and evaluation of irritants on human skin. J.Invest.Derm. 49: 78-94, 1967). One, five and ten percent concentrations of S-1333 were applied daily to the forearms of ten young adult female college student. Reactions were scored daily as follows:
0 = no reaction;
1 = mil d erythema;
2 = moderate erythema;
3 = intense erythema and edema.

Test on scarified skin:
The chamber scarification method was used (Frosch, P.J. and A.M. Kligman: The chamber-scarification test of irritancy. Contact Dermatitis 2: 314-324, 1976). One, five and ten percent concentrations were applied once daily for three days to scarified skin (eight rightangle scratches without bleeding) . The sites were scored daily.
1 = redness confined to scratches;
2 = spreading redness;
3 = confluent redness and edema;
4 = intense redness and confluent swelling.
Exposure assessment:
measured
Details on exposure:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): no data
- Concentration (if solution): Test on intact and scarified skin: 1 %, 5 % and 10 %

VEHICLE: water

Results and discussion

Any other information on results incl. tables

Test on intact skin:

1 %: 1% of S-1333 produced no visible reaction in any of the subjects. All scores zero.

5 %: By the sixth day, some (3/10) of the volunteers treated with 5% of S-1333 began to exhibit mild erythema (score 1) which gradually worsened thereafter. At treatment day 10 2/10 volunteers had skin reactions score 1 and 8/10 skin reactions score 2.

10 %: The results with 10% were indistinguishable from the 5% concentration. First skin reactions were visible on treatment day 6 (4/10 volunteers with skin reactions score 1). At treatment day 10 1/10 volunteer had skin reactions score 1 and 9/10 volunteers skin reactions score 2.

According to the discussion of the study author, five and ten percent S-1333 are mildly irritating when applied under continuous occlusion. The latter mode of exposure is, of course, greatly exaggerated in relation to normal use.

Test on scarified skin:

1 %: One percent was mildly irritating in three of ten subjects by the third day.

5 %: 5% was markedly irritating from the beginning. At the first day 5/10 volunteers had skin reactions score 1 and 5/10 volunteers skin reactions score 2. The skin reactions worsend until day 3 (8/10 volunteers with score 3 and 2/10 volunteers with score 4).

10%: 10 % was somewhat worse than 5% (at the first day 1/10 volunteers with score 1 and 9/10 volunteers with score 2; at day 3 3/10 volunteers with score 3 and 7/10 volunteers with score 4).

According to the discussion of the study author, S-1333 is irritating when applied continuously for three days to skin in which the "barrier" to penetration has been breached by scratching. S-1333 in concentrations of 5% and 10% could be potentially irritating on damaged skin.

Applicant's summary and conclusion

Executive summary:

In a human patch test, according to the method of Kligman and Wooding 1967, 1 %, 5 % and 10 % solutions of S-1333 were applied daily to the forearms under occlusive dressing for 24 hours, on 10 consecutive days to 10 young adult female volunteers. Scores were recorded daily on a scale from 0 – 3.

1% of S -1333 produced no visible reactions in any of the subjects. At day 6 the development of an increasing skin reaction was observed at 5 and 10 %, with a similar intensity for both concentrations. Score 2 was observed in 8/10 (5 %) and 9/10 (10 %) at day 10, whereas in the remaining subjects a score of 1 was observed.

As judged by the study authors five and ten percent S-1333 were mildly irritating when applied under continuous occlusion. The latter mode of exposure is, of course, greatly exaggerated in relation to normal use.

In an additional human patch test using the chamber-scarification method, according to Frosch and Kligman 1976, 1 %, 5 % and 10 % solutions of S-1333 were applied once daily for 3 days and a 24 hour period to scarified skin of 10 volunteers. Scores were recorded daily on a scale from 1 – 4.

A concentration of 1 % was mildly irritating in 3/10 subjects by the third day.  Irritation was observed from the first scoring with increasing intensity. At day 3 for the 5 % test substance score 3 was observed in 8/10 and score 4 in 2/10 subjects. A somewhat worse reaction was observed at 10 % with score 3 in 3/10 and score 4 in 7/10 subjects respectively.

As judged by the study authors S -1333 is irritating when applied continuously for three days to skin in which the "barrier" to penetration has been breached by scratching. S-1333 in concentrations of 5% and 10% could be potentially irritating on damaged skin.

Solids content of Rewoderm S -1333 according to producers information: minimum 39 %. Taking this value into account, solid content of the test solutions was 0.39, 1.95 and 3.9 %, respectively, in minimum.