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Administrative data

Description of key information

2 skin irritation/corrosion studies conducted in vivo in New Zealand white rabbits

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Standard OECD Guideline study conducted according to GLP
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Housing: The animal was singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times per week.

Animal Room Temperature: 19-21°C
Relative Humidity: see Section 9
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 8 days
Feed: Purina Certified High Fiber Rabbit Diet (PMI #5325).
Water: Filtered tap water was supplied ad-libitum by an automatic water dispensing
system.

Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with the results of this study. Analysis of the water is conducted at least once a year and the records are kept on file at Eurofins | Product Safety Laboratories. The most recent analysis was conducted in September 2006.
Purina Certified High Fiber Rabbit Diet, PMI #5325, Lot Number:
JUL 08 06 3A, was analyzed in July 2006.

Cage: The cage was identified with a cage card indicating at least the study number and identification and sex of the animal.
Animal: A number was allocated to the rabbit on receipt and a stainless steel ear tag bearing this number was attached to the animal. This number, together with a sequential animal number assigned to study 20361, constituted unique identification.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml of neat test substance was applied to the dose site (6 cm2 in dimension)
Duration of treatment / exposure:
1 hour
Observation period:
The study was terminated at the 1 hour time point due to necrosis
Number of animals:
1, Female. The animal assigned to test was nulliparous and non-pregnant.
Details on study design:
Initial testing was conducted on one rabbit to determine the irritation/corrosion potential of the test substance. Three test sites, each approximately 6-cm2, were delineated on this rabbit. Five-tenths of a milliliter of the test substance was applied to each dose site and covered with a 1-inch x 1-inch, 4- ply gauze pad. The pad and entire trunk of each animal were then wrapped with semi-occlusive 3- inch Micropore tape to avoid dislocation of the patch. The patches were removed at the appropriate intervals (3 minutes and 1-hour). The test sites were evaluated for corrosion 30-60 minutes after patch removal. Due to corrosion at the 1-hour test site, the 4-hour patch was removed at the same time as the 1-hour patch.
Irritation parameter:
other: Necrosis
Basis:
animal #1
Time point:
other: 1 hour
Reversibility:
other: study terminated after 1 hour so reversibility not assessed
Remarks on result:
other: substance was corrosive
Irritant / corrosive response data:
Substance was corrosive after 1 hour of exposure

The animal appeared active and healthy during the study. Apart from the skin irritation/corrosion noted below, there were no other signs of gross toxicity, adverse clinical signs, or abnormal behavior. One hour after patch removal, from the 3-minute dose site, well-defined erythema and slight edema were noted. Severe erythema, slight edema, and corrosion were noted at the 1-hour site one hour after patch removal. Due to corrosion noted at the 1-hour test site, the study was terminated and the animal was euthanized for humane reasons.

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, XU-12314.00 caused corrosion to the skin when applied for one
hour.
Executive summary:

A primary skin irritation test was conducted with a single rabbit to determine the potential for XU- 12314.00 to produce irritation and/or corrosion after topical application. Under the conditions of this study, the test substance was corrosive to the skin. Initially, one rabbit was tested to determine the irritation/corrosion potential of the test substance. Three test sites, each approximately 6-cm2, were delineated on this animal. Five-tenths of a milliliter of the test substance was applied to each dose site and covered with a 1-inch x 1-inch, 4-ply gauze pad. The pad and entire trunk of the animal was then wrapped with semi-occlusive 3-inch Micropore tape to avoid dislocation of the patches. The patches were removed at the appropriate intervals (3 minutes and 1- hour). The test sites were evaluated for corrosion 60 minutes after patch removal. Due to corrosion at the 1-hour test site, the 4-hour patch was removed at the same time as the 1-hour patch. The 3-minute and 1- hour test sites were also evaluated for skin irritation according to the Draize1 scoring system at 60 minutes after the patch removal. Since corrosion was noted at the 1-hour test site, the study was terminated and the animal was euthanized for humane reasons. One hour after patch removal, well-defined erythema and slight edema were noted at the 3-minute dose site. Severe erythema, slight edema, and corrosion were noted at the 1-hour site one hour after patch removal. Due to corrosion noted at the 1-hour test site, the study was terminated and the animal was euthanized for humane reasons.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Ocatanolamine was corrosive to the skin of albino rabbits when administered 'neat' or when pH adjusted to pH 9.5.

Due to the corrosion observed with both buffered and unbuffered octanolamine it was considered unnecessary and inappropriate to conduct an eye irritancy study.


Justification for selection of skin irritation / corrosion endpoint:
stnadard guideline study

Justification for selection of eye irritation endpoint:
no study conducted due to corrosivity of substance to skin

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Due to the necrosis seen at the 1 hour time point rather than the 3 minute time point Octanolamine meets the criteria for 'Corrosive' (EU DSD).

It also meets the criteria for classification as Corrosive, sub category 1B according to the GHS criteria since necrosis was seen at the 1 hour time point rather than the 3 minute time point.

No classification is considered necessary for respiratory irritation since the substance is corrosive and this overrules any additional classifications for respiratory irritancy.