Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline study, limitations in design and/or reporting but otherwise adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Skin irritation patch test, as described in Federal Register 1973, Vol. 38, No. 187, Section 1500: 41.
Deviations:
not specified
Principles of method if other than guideline:
Occluded application of test material to shaved abraded and intact skin of six rabbits and assessed for primary irritation.
GLP compliance:
no
Remarks:
Conducted prior to requirement for GLP

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Ammonium perrhenate
- Substance type: white powder
- Physical state: solid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: “recognised breeders”
- Age at study initiation: 16-18 weeks
- Weight at study initiation: 2.4 kg (average)
- Diet: ad libitum commercial rabbit diet supplied by Rank Hovis MacDougal
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): “natural lighting conditions”

Test system

Type of coverage:
occlusive
Preparation of test site:
other: Backs of the rabbits were shaved (not “closely clipped” as recommended by the OECD guidelines). One site on each rabbit was abraded immediately before application of the test materials, the other site remained intact.
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): “sample was moistened with sterile distilled water”
Duration of treatment / exposure:
24 hrs
Observation period:
48 hrs after removal of patch
Number of animals:
Six females
Details on study design:
TEST SITE
- Area of exposure: each site 2.5 cm2 (one site intact, one site abraded)
- Type of wrap if used: Gauze pad was secured by “Sleek” adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

SCORING SYSTEM: Oedema and erythema (and eschar) formation were assessed on the non-abraded and abraded skin of six rabbits 24 and 72 hrs after the initial application of the test material (i.e. as soon as the dressing was removed and again 48 hr later). The primary irritation index was then calculated by adding the four values for eryhtema (and eschar) formation to the four for oedema formation, and dividing the total by four. According to the study report, Draize (1959) considers that “compounds producing combined averages (primary irritation indices) of 2 or less are only mildly irritating; whereas those with indices of 2 to 5 are moderate irritants, and those with scores above 6 are considered severe irritants”.

Results and discussion

In vivo

Results
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hrs after initial application.
Score:
0.08
Reversibility:
other: Reversibility was not assessed as the observation period was only for 48 hrs after removal of the patch (not up to 14 days as recommended in the OECD guidelines).
Irritant / corrosive response data:
See Individual rabbit results under Attached background material, below.
Other effects:
The systemic toxicity was not reported.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Ammonium perrhenate (0.5 g) produced a primary irritation index of 0.08 following occluded application to the shaved abraded and intact skin of six rabbits, and therefore would be classified at most as only a mild irritant in this test system. This study was not performed to current guidelines.
Executive summary:

Ammonium perrhenate (0.5 g) was applied (occluded) to the shaved abraded and intact skin of six female rabbits. After 24 hrs, the dressings were removed and the abraded and intact skin sites were quantitatively assessed for erythema (and eschar) formation and oedema formation. Readings were again made 48 hrs later. Slight reddening (“barely perceptible”) was seen in one rabbit, 24 and 72 hours following exposure, only on the abraded skin. No other reactions were observed in any other animals. Overall scores were combined and divided by four to give a primary irritation score or 0.08, which would be deemed to be at most only mildly irritating in this test system. This study suffered from a number of significant deviations when compared with current OECD guidelines, including use of abraded skin, a longer exposure period and failure to wash off any residual test material after removal of the patch, observation period was insufficient to assess reversibility of effects, and skin was only examined on 2 occasions, at 0 and 48 hrs, rather than at 1, 24, 48 and 72 hrs, after removal of the patch. However, certain of these deviations would likely increase the possibility of an irritant reaction and thus ammonium perrhenate would be unlikely to cause significant skin irritation in a study performed to current OECD guidelines.