Feropur

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to the EU RAR for Sodium Hydroxide (2007; section 4.1.2.3.1), a Klimisch 1 reliability score was assigned since the test procedure is in accordance with generally accepted scientific standards and described in sufficient detail.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Evaluation of a human patch test for the identification and classification of skin irritation potential

Author:

York M, Griffiths E, Whittle E and Basketter DA

Year:

1996

Bibliographic source:

Contact Dermatitis, 34, 204-212

Materials and methods

Principles of method if other than guideline:

Treatment sites were assessed for the presence of irritation using a 4 point scale at 24, 48 and 72 hours after patch removal. Sodium dodecyl sulfate (20 %) was used as a positive control and is the minimum concentration classified as "irritating to skin" (R38) under EU regulations.

GLP compliance:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): Sodium hydroxide (NaOH)
- Other: source is Sherman

Test animals

Species:

human

Strain:

not specified

Details on test animals or test system and environmental conditions:

HUMAN VOLUNTEERS
- Sex distribution in the individual panels was not standardized
- Age: 18 to 65 years
- Normal healthy volunteers

Test system

Type of coverage:

other: patch - 25 mm Hill Top chamber containing a Webril pad (occluded exposure)

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

other: SDS (20%) was used as positive control

Amount / concentration applied:

Concentration: 0.5 %
Total volume applied: 0.2 ml

Duration of treatment / exposure:

To avoid the production of unacceptably high reactions a cautious approach to testing was adopted. Test materials were applied progressively from 15 and 30 min through 1, 2, 3 and 4 h. The 15 and 30 min exposure periods were omitted if the Study Directors were satisfied that excessive reactions would not occur following the 1 h exposure.

Observation period:

Examination time points: 24, 48 and 72 hours after patch removal

Number of animals:

Number of volunteers: 33

Details on study design:

TEST SITE
- Area of exposure: upper outer arm

SCORING SYSTEM: 0 (no reaction)- +++ (strongly positive reaction)

Results and discussion

In vivo

Irritant / corrosive response data:

The total number of "positive" reactions was 20 of the 33 subjects after 1 hour, which is higher than SDS (20 %) after 1 hour (4 of 33 subjects) but less than the 4 hour reaction to SDS (23/33).

Any other information on results incl. tables

Human patch testing with Hill Top chambers for up to 4 h; total reactivity to NaOH (relative to SDS (20%) reference solution) and existing and proposed EU classification:

Existing EU classification	Total reactivity at 4 h (% reactivity)	Comparable 20% SDS reactivity (%)	Classification based on human patch test
R38	20/33 (61)*	4/33 (12)**	R38
		20/33 (70)***

R38: Irritating to skin

*: maximum exposure 1 h because of strong level of response

**: 1h exposure

***: 4 h exposure

Similar results for sodium hydroxide (0.5%) are reported in the publication of Griffiths et al.(1997) where the patch test procedure of York et al. was used in an interlaboratory test to validate an alternative (in vivo) method to the Draize skin irritation test involving use of human volunteers to identify skin irritation hazard. The study was performed in three different test facilities (Unilever, proDerm and P&G). The Unilever results are summarised in the table above. Following results were obtained from proDerm and P&G:

Test group	Dates	No of (+)ve reactions*	No of (+)ve SDS reactions*	HPT Class§
proDerm	Nov/Dec 94	13/31 (42)**	1/31 (3)**	R38
			22/31 (71)
P&G	Sep/Oct 95	21/34 (62)**	7/34 (21)**	R38
			32/34 (94)

*Results are presented as the proportion of the test panel giving an irritant response, with percentages in parentheses

§EC classification based on the results of the human 4 hr patch test (HPT); the substance is not classified if the proportion of the panel reaching to it is not significantly less than that to the concurrent positive control using the Fisher's exact test

**Results at 1 hour of exposure.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information 0.5% NaOH; for exposure up to 1 hour

Conclusions:

NaOH was identified as R38 "Irritating to the skin". The "irritant" classification for NaOH (0.5%) may be an underestimation, based on the intensity of the response in a large proportion of the panel after only 1h of treatment.