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Description of key information

Results of the histopathological examination of lung tissue acutely exposed to zinc dilaurate via inhalation (OECD 436 test) do not indicate an irritative potential of fatty acid zinc salts. Studies on skin and eye irritation performed on zinc salts of shorter-chained (C8,12) and similar chained (C16 -18) fatty acids demonstrate further the lack of irritation/corrosion potential.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1992-10-20 to 1992-10-29
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 1981-05-12
GLP compliance:
yes
Species:
rabbit
Strain:
other: Kleinrussen, CHbb:HM
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Thomae GmbH, Biberach/D.
- Age at study initiation: approx. 9 months
- Weight at study initiation: approx. 2590 g
- Housing: individual accommodation in cages
- Diet (ad libitum): Ssniff rabbit diet K4 (Ssniff GmbH, Soest/D, Batch: 770992/09)
- Water (ad libitum): tap water
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: approx. 20-25 °C
- Relative humidity: approx. 45-70 %
- Air changes: at least eight per hour
- Photoperiod (hrs dark / hrs light): 12/12
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): the undiluted test substance Stabiol VZN 1950 was applied at the dose level of 0.5 g per animal.
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after exposure
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
- Area of exposure: the flank of each experimental animal was sheared approx. 24 hours prior to the application with an electric clipper. Animals with intact and healthy skin were used in the test.
The semi-occlusive exposure was performed by means of a 6 cm^2 adhesive air- and vapour permeable gauze-patch which was fixed by a hypoallergic adhesive gauze-bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the exposure was terminated after four hours by removing the patch and cleaning the relevant skin from the residual test substance.

SCORING SYSTEM: according to Draize scale
Irritation parameter:
erythema score
Basis:
animal: #1, #2, #3
Time point:
other: mean 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal: #1, #2, #3
Time point:
other: mean 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
No dermal effects were observed at all experimental animals up to 72 hours after exposure.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Octanoic acid, zinc salt, basic is not irritating to the skin.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is not classified as skin irritant.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as skin irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2011-12-08 to 2011-12-18
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across of a GLP guideline study RL1
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted April 24, 2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
2008
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2009-11-12
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
- Source: LPT Laboratory of Pharmacology and Toxicology GmbH Co. KG, Branch Löhndorf, 24601 Löhndorf/Post Wankendorf, Germany
- Age at study initiation: approx. 4.5- 5.5 months
- Weight at study initiation: 2.5 - 2.8 kg
- Housing: animals were kept singly in cages of 380 mm x 425mm x 600 mm (manufacturer: Dipl. Ing. W. EHRET GmbH, 16352 Schönwalde, Germany) during the acclimatisation period and after the 8 hours period in restrainers (for 8 hours following test item application the animals were kept singly in restrainers).
- Diet (ad libitum): commercial diet, ssniff K-H V2333 (Ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum before and after the exposure period): tap water
- Acclimation period: at least 20 adaptation days

ENVIRONMENTAL CONDITIONS:
- Temperature: 20°C ± 3°C (maximum range)
- Relative humidity: 30% to 70 % (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL:
- Amount(s) applied (volume or weight with unit): 100 mg
Duration of treatment / exposure:
1 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
INITIAL AND CONFORMATORY TEST
The test was performed initially using one animal. As no corrosive or severe irritant effects were observed in this animal, 2 further animals were employed 24 hours after start of the initial test.

The test item were administered into one eye each of three animals. The test item was placed into the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second in order to prevent loss of the material. The left eye, which remained untreated, served as a control.

APPLICATION
- 100 mg of the test item were administered into one eye each of three animals. The volume of particulates was measured after gently compacting them, e.g. by tapping the measuring container. The test item was placed into the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second in order to prevent loss of the material. The left eye, which remained untreated, served as a control.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the eyes were rinsed with portions of 20 mL 0.9% aqueous NaCl solution, each.
- Time after start of exposure: 1 hour after administration

SCORING SYSTEM: according to the Draize scale
Any further lesions are listed.

TOOL USED TO ASSESS SCORE: the eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48 and 72 hours after the administration. The eye reactions were observed and registered.
24 hours and after administration, fluorescein (Fluorescein SE Thilo drops (ALCON PHARMA GmbH, 79108 Freiburg, Germany) was applied to the eyes before being examined to aid evaluation of the cornea for possible lesions.

OBSERVATIONS
Body weight of all animals was measured at the beginning of the study. Behaviour and food consumption were monitored.
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
other: mean 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Time point:
other: mean 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal: #1, #2
Time point:
other: mean 24, 48, 72 hours
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Time point:
other: mean 24, 48, 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal: #1, #2, #3
Time point:
other: mean 24, 48, 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
Conjunctival redness (grade 1) was observed in all animals for 60 minutes, and in one animal for 24 hours after the instillation.
The corneae and irises were not affected by instillation of the test item.
The fluorescein test performed 24 hours after instillation did not reveal any changes.
Other effects:
There were no systemic intolerance reactions.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material is non-irritating to the eyes.
According to 67/548/EC and subsequent regulations, the substance is not classified as an eye irritant.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the substance is not classified as an eye irritant.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Zinc bis[12-hydroxyoctadecanoate]:

Zinc bis[12-hydroxyoctadecanoate] is a zinc salt of a fatty acid containing 18 C-atoms. Thus, read-across of data available for zinc salts of shorter-chained (C8, C12) and similar chained (C16-18) fatty acids based on structural similarity, water solubility and zinc content in a conservative, worst-case approach is assumed to adequately describe the toxicological potential of zinc bis[12-hydroxyoctadecanoate]. The irritation and corrosion potential is described with information read-across from relevant zinc soaps (zinc salts of shorter-chained (C8, C12) and similar-chained (C16 -18) fatty acids) as well as supporting information from slightly soluble/insoluble zinc compounds. A 1:1 read-across of toxicological data of (i) octanoic acid, zinc salt, basic; (ii) Fatty acids, C16-18, zinc salts; and (iii) zinc oxide is applied to zinc bis[12-hydroxyoctadecanoate] as it is assumed that during exposure zinc bis[12-hydroxyoctadecanoate] would be changed (at least in part) to ionic zinc and its fatty acid moiety. Consequently following the worst-case approach, the studies on the fatty acid zinc salt with highest zinc amount and lowest pH of the non-saponified free fatty acid were selected. Octanoic acid, zinc salt, basic (C8) is not irritating to the skin and zinc dilaurate (C12) is not irritating to the eye. In addition, the results of the histopathological examination of lung tissue acutely exposed to zinc dilaurate via inhalation (OECD 436 test) do not indicate an irritative potential. Furthermore, zinc bis[12-hydroxyoctadecanoate] is not expected to be irritating to the skin or the eye based on the lack of respective irritation potential of zinc salts of similar-chained (C16 -18) fatty acids as well as supporting information from slightly soluble/insoluble zinc compounds. Thus, a lack of skin, eye and respiratory irritancy is considered for Zinc bis[12-hydroxyoctadecanoate], and classification according to Directive 67/548/EEC and Regulation (EC) 1272/2008 is not required. These conclusions are in line with conclusions for the structural analogue (i.e. Fatty acids, C16 -18, zinc salts) from EU RAR “Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II – Human Health. EUR 21168 EN (http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1):

"It is consequently concluded that zinc distearate is not likely to have eye and skin irritation potential and, therefore does not need to be classified/labelled... Zinc distearate is not corrosive to skin or eyes."

A similar lack of skin and eye irritancy is considered for zinc bis[12-hydroxyoctadecanoate]. For a comprehensive overview of the (non) irritancy of zinc, see the hazard assessment of "Zinc" within the framework of Regulation (EC) No 1907/2006 below.

 

ZINC:

Based on the available information it appears that he slightly soluble zinc oxide and insoluble zinc sulphide are not skin irritants and therefore slightly soluble zinc hydroxide, zinc phosphate, zinc carbonate and zinc metal are also expected to be not irritating to skin. Zinc oxide, zinc phosphate, zinc metal and zinc sulphide are not eye irritants and therefore zinc carbonate and zinc hydroxide are also expected to be not irritating to eyes. None of the slightly soluble or insoluble zinc compounds appear to cause respiratory tract irritation.

The slightly soluble and insoluble zinc compounds (zinc oxide, zinc hydroxide, zinc phosphate, zinc carbonate, zinc metal and zinc sulphide) are not corrosive based on the available irritation data.


Justification for selection of skin irritation / corrosion endpoint:
Different reliable, relevant and adequate studies conducted with different zinc compounds are read-across to address this endpoint, (i) zinc oxide; (ii) Fatty acids, C16-18, zinc salts; and (iii) octanoic acid, zinc salt, basic. Consequently following the worst-case approach, the study on the fatty acid zinc salt with highest zinc amount and lowest pH of the non-saponified free fatty acid (octanoic acid, zinc salt, basic) was selected. Based on the whole data base, zinc bis[12-hydroxyoctadecanoate] is not considered to be irritating to the skin.

Justification for selection of eye irritation endpoint:
Different reliable, relevant and adequate studies conducted with different zinc compounds are read-across to address this endpoint, (i) zinc oxide; (ii) Fatty acids, C16-18, zinc salts; and (iii) zinc dilaurate. Consequently following the worst-case approach, the study on the fatty acid zinc salt with highest zinc amount and lowest pH of the non-saponified free fatty acid (zinc dilaurate) was selected. Based on the whole data base, zinc bis[12-hydroxyoctadecanoate] is not considered to be irritating to the eyes.

Justification for classification or non-classification

Zinc bis[12-hydroxyoctadecanoate] as slightly soluble/insoluble zinc compound is not irritating or corrosive based on the available irritation data. Therefore, classification is not required for irritation or corrosion according to EC criteria outlined inCLP Regulation (EC) No 1272/2008 and Directive 67/548/EEC .