Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
02 February 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Oleyl tripropylenetetramine
- Substance type: white paste
- Physical state: solid
- Analytical purity: see attached certificate of analysis
- Impurities (identity and concentrations): Free acrylonitrile <4 ppm, water: 0.1 %)
- Composition of test material, percentage of components: see attached certificate of analysis
- Purity test date: 5 February 2009
- Lot/batch No.:S001029
- Expiration date of the lot/batch: 14 May 2017
- Stability under test conditions: stable
- Storage condition of test material: At room temperature in the dark under Nitrogen

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan, Belton, Leics, England.
- Age at study initiation: at least 6 weeks
- Weight at study initiation: at least 1.0 kg
- Housing: The animal was individually housed in a labeled cage with perforated floor and shelter
- Diet: ad libitum
- Water: ad libitum)
- Acclimation period: Acclimatization period was at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.8 - 20.6ºC
- Humidity (%): 44 - 74%
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 02 February 2010

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 grams

pH (1% in water, indicative range): 10.2-10.7

Duration of treatment / exposure:
3 minutes, 1 hour and 4 hours:
The study was initiated by treatment of one rabbit. This animal received of 0.5 grams of the test substance to the intact, clipped skin of one flank using a Metalline patch of 2x3 cm. The patch was mounted on Micropore tape#, which was wrapped around the abdomen and secured with Coban elastic bandage. The dressing was removed 3 minutes after application. Since no signs of severe skin reactions (i.e. necrosis or corrosion) were observed and it was considered that exposure could be continued humanely, two samples of 0.5 grams of the test substance were then applied to separate skin-sites on the intact, clipped skin of the same animal, using an identical procedure and one sample per dressing. One of the dressings was removed after a 1-hour exposure. After similar considerations (i.e. no severe skin reactions, necrosis or corrosion), the other dressing was removed after a 4-hour exposure. Since signs of severe skin reactions (i.e. necrosis) were observed after 4 hours of exposure, the study was immediately terminated, and no further testing was performed.
Observation period:
up to 4 hours after the first application when the single treated animal was sacrificed for ethical reasons.
Number of animals:
1 (based on the severe skin reactions, no further animals were exposed to the test substance)
Details on study design:
TEST SITE
- Area of exposure: 2x3 cm
- Type of wrap if used: Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): water and ethanol
- Time after start of exposure: immediately

SCORING SYSTEM:
The skin reactions of all visible treated sites were assessed immediately after removal of a dressing. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of untreated skin of the animal served as controls.

The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

Erythema and eschar formation:
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) * 4
*. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the
maximum grade for erythema (= 4) is given.

Oedema formation:
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimeter) 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Other observations:

Mortality/Viability Twice daily.

Toxicity At least once daily.

Body Weight Day of treatment (prior to application).

Necropsy No necropsy was performed.


Results and discussion

In vivo

Irritant / corrosive response data:
A 3-minute exposure to 0.5 g of Oleyl tripropylenetetramine resulted in very slight erythema at 1 and 4 hours after exposure.

A 1-hour exposure resulted in very slight erythema immediately after exposure and in well defined erythema at 3 hours after exposure.

A 4-hour exposure resulted in dark brown discolouration surrounded by grey discolouration at the edge of the application area (sign of necrosis) immediately after exposure.
Other effects:
Sticky or dry remnants of the test substance were present on the skin after exposure.

Any other information on results incl. tables

See attached table Individual irritation scores.

Applicant's summary and conclusion

Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Oleyl tripropylene tetramine (C18 tripropylene tetramine) should be classified as : skin corrosive (Category 1C).
Executive summary:

One rabbit was exposed to three samples of 0.5 grams of Oleyl tripropylene tetramine (C18tripropylene tetramine) applied to separate skin-sites on intact, clipped skin using a semi-occlusive dressing. The exposure periods were 3 minutes, 1 hour and 4 hours, respectively. Skin reactions were assessed up to 4 hours after the 3-minute exposure. Based on severe skin reactions, no further animals were exposed to the test substance. A 3-minute exposure to 0.5 g of Oleyl tripropylenetetramine (C18tripropylene tetramine) resulted in very slight erythema at 1 and 4 hours after exposure.

A 1-hour exposure resulted in very slight erythema immediately after exposure and in well defined erythema at 3 hours after exposure.

A 4-hour exposure resulted in dark brown discolouration surrounded by grey discolouration at the edge of the application area (sign of necrosis) immediately after exposure.

Sticky or dry remnants of the test substance were present on the skin after exposure. The dark brown discolouration surrounded by grey discolouration at the edge of the application area are signs of necrosis. Following this observation, the animal was sacrificed for humane reasons. These severe skin reactions are expected to result in deep and thick scab formation with possible ruptures of the scab, or the scab may drop off exposing scar tissue. Overall, these skin reactions were considered evidence of full thickness destruction of the skin, and hence no further animals were tested. Based on these results Oleyl tripropylene tetramine (C18tripropylene tetramine) should be considered corrosive to skin.