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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 August 2010 to 18 August 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Available data from Etheramine C13i are considered to be applicable for C10i-etheramine as well. The structure of Etheramine C13i only differs from that of Etheramine C10i, in that the alkyl chain is only 2 carbons longer. This only has limited effects on physical properties, whereas chemical behaviour, reactivity and metabolism are the same. With alkylamines in general, the corrosive properties tend to increase with shortening of the alkyl chain. Therefore the results obtained from Etheramine C13i are therefore also expected to be of similar severity for Etheramine C10i, but certainly not less severe.

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
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3-(Isotridecyloxy)-1-propane amine
- Chemical name (IUPAC): 3-[(11-methyldodecyl)oxy]propan-1-amine
- Substance type: Clear colourless liquid
- Physical state: liquid
- Analytical purity: 95.8% m/m (NMR)
- Lot/batch No.: S001287
- Expiration date of the lot/batch: 30 April 2018
- Stability under storage conditions: Stable
- Storage condition of test material: At room temperature in the dark
- Density: 840 kg/m3
- pH: 11

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Source: Harlan, Belton, Leics, England
- Age at study initiation: at least 6 weeks old.
- Weight at study initiation: at least 1.0 kg.
- Housing: Animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
- Diet (e.g. ad libitum): Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) was provided at least three times a week.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: The acclimatization period was at least 5 days before the start of treatment under laboratory conditions.

A health inspection was performed prior to treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.

Results of analysis for diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.

Animal specifications (sex, age and body weight) are specified in the attached table.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.2 – 20.3ºC
- Humidity (%): 50 - 82%
Deviations from the maximum level of relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.
- Air changes (per hr): approximately 15 air changes per hour- Photoperiod (hrs dark / hrs light): 12 hours artificial
fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 03 August 2010 to 18 August 2010

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: Adjacent areas of the untreated skin of each animal served as controls.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
Single application.
Observation period:
14 days.
Number of animals:
1 male.
Details on study design:
STUDY DESIGN
The study was performed in a stepwise manner and started with the treatment of one animal (sentinel) with a stepwise exposure regime. Based on the severity of the skin reactions, no further animals were exposed.

TEST SUBSTANCE PREPARATION
The test substance was applied as delivered by the sponsor.

TEST SITE
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.

The test substance was applied to the 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#.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.

After the final observation, the animal was sacrificed by intra-venous injection of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands).

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to application) and after the final observation.
- Necropsy: The treated animal was subjected to necropsy and a description of all internal macroscopic abnormalities was recorded.
- Irritation:
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours and 7 and 14 days after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded.

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

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

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

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(mean)
Time point:
other: 24, 48 and 72 hours, 7 and 14 days
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
(mean)
Time point:
other: 24, 48 and 72 hours, 7 and 14 days
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
A 3-minute, 1- and 4-hour exposure to 0.5 mL of 3-(Isotridecyloxy)-1-propane amine resulted in erythema and oedema in the treated skin areas. Up to very slight erythema and oedema was observed on Day 1, progressing into severe erythema and oedema from 24 hours after exposure on all treated skin sites. The skin irritation remained present up the end of the observation period (14 days after exposure) on all treated skin sites. Reduced flexibility of the skin was observed between 24 hours and 7 days after exposure on all treated skin sites. A dry wound was visible at 7 days after exposure on the 3-minute skin site, and at 72 hours and 7 days after exposure on the 1- and 4-hour skin site. A bald, noticeable white skin (indicating full thickness destruction of the skin), and superficial red-brown eschar formation was observed at 14-days after exposure on all treated skin sites.

Tables containing individual and mean irritation scores are specified in the attached table.
Other effects:
No staining of the treated skin by the test substance was observed, and no remnants of the test substance were observed on the skin on Day 1.

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Remarks:
Migrated information
Conclusions:
3-(Isotridecyloxy)-1-propane amine is corrosive to the rabbit skin following 3 minutes exposure.
Executive summary:

Primary skin irritation/corrosion study with 3-(Isotridecyloxy)-1-propane amine in the rabbit (semi-occlusive application) according to OECD 404.

One rabbit was exposed to three samples of 0.5 mL of 3-(Isotridecyloxy)-1-propane amine 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 at least once daily for 4 days after treatment and 7 and 14 days after exposure. Based on the severity of the skin reactions, no further animals were exposed.

Exposure to 3-(Isotridecyloxy)-1-propane amine resulted in erythema and oedema in the treated skin areas. Up to very slight erythema and oedema was observed on Day 1, progressing into severe erythema and oedema from 24 hours after exposure on all treated skin sites. The skin irritation remained present up the end of the observation period (14 days after exposure) on all treated skin sites. Reduced flexibility of the skin was observed between 24 hours and 7 days after exposure on all treated skin sites. A dry wound was visible at 7 days after exposure on the 3-minute skin site, and at 72 hours and 7 days after exposure on the 1- and 4-hour skin site. A bald, noticeable white skin (indicating full thickness destruction of the skin), and superficial redbrown eschar formation was observed at 14-days after exposure on all treated skin sites.

The bald, noticeable white skin observed at 14-days after exposure on all treated skin sites was indicative of full thickness destruction of the skin, and indicated that corrosion of the skin had occurred by dermal application of 3-(Isotridecyloxy)-1-propane amine to the intact rabbit skin.

 

Based on these results and according to the:

-Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007), 3-(Isotridecyloxy)-1-propane amine should be classified as : skin corrosive (Category 1B).

- Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures, 3-(Isotridecyloxy)-1-propane amine should be classified as Corrosive (Category 1B) and labeled as H314: Causes severe skin burns and eye damage.