Registration Dossier

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Administrative data

Description of key information

No acute toxicity studies with Fatty acids, C8-10, zinc salts are available, thus the acute toxicity will be addressed with existing data on the dissociation products zinc and fatty acids, C8-10 and with existing data on structurally similar zinc salts of fatty acids.

 

Signs of acute oral and dermal toxicity are not expected for Fatty acids, C8 -10, zinc salts, since the moiety zinc has not shown signs of acute oral toxicity in experimental testing and the acute dermal toxicity for the moiety zinc can be considered low in view of the poor absorption by this route. For the moiety fatty acids, C8-10 there were no toxicological findings reported in peer-reviewed publicly available assessment reports, neither by the oral nor by the dermal route.

 

The calculated oral and dermal LD50 for fatty acids, C8-10, zinc salts is > 2000mg/kg, hence the substance is not to be classified according to regulation (EC) 1272/2008 for acute oral and dermal toxicity as well as for specific target organ toxicity, single exposure (STOT SE).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-01-13 to 2012-02-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Fatty acids, C8 -10, zinc salts is a zinc salt of a short-chained fatty acids containing 8 -10 C-atoms. Thus, read-across of data available for zinc salts of short-chained (C8, C12) and longr-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 fatty acids, C8 -10, zinc salts. Acute toxicity is addressed with data read-across from relevant zinc soaps (zinc salts of short-chained (C8, C12) and long-chained (C16 -18) fatty acids), including (i) octanoic acid, zinc salt, basic (C8), (ii) zinc dilaurate,(iii) zinc bis[12 -hydroxy-octadecanoate, and (iv) Fatty acids, C16-18, zinc salts,as well as supporting information from slightly soluble/insoluble zinc compounds.

Regarding acute oral toxicity, a reliable GLP study conducted with octanoic acid, zinc salt, basic (C8) is read-across to address this endpoint.
Different reliable studies conducted with different zinc compounds are read-across as supporting information, including (i) zinc oxide; (ii) Fatty acids, C16-C18, zinc salts; (iii) zinc bis [12-hydroxy-octadecanoate]. Based o the lack of an acute toxicity potential of a zinc salt of a similar chained (C8) fatty acid and zinc salts of longer-chained (C16 -18) fatty acids and slightly soluble/insoluble zinc substances, the LD50 for fatty acids, C8 -10, zinc salts was estimated to be greater than 2000 mg/kg bw.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 2001-12-17
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
May 30, 2008)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2009-11-12
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
- Source: Charles River Laboratories, Research Models and Services, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: 167 - 182 g
- Fasting period before study: feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum.
- Housing: during the 14-day observation period the animals were kept in groups of 3 animals in MAKROLON cages (type III plus). Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages.
- Diet (ad libitum): commercial diet, ssniff R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum): drinking water
- Acclimation period: at least 5 adaptation days

ENVIRONMENTAL CONDITIONS:
- Temperature: 22°C ± 3°C (maximum range)
- Relative humidity: 55% ± 15% (maximum range)
- Air changes: 12 to 18- fold air change per hour
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: 0.8% aqueous hydroxypropylmethylcellulose
Details on oral exposure:
VEHICLE
- Methocel; batch no. 11 A 27-N27, Fagron GmbH & Co., 22885 Barsbüttel, Germany

MAXIMUM DOSE VOLUME APPLIED: the administration volume was 10 mL/kg bw.

DOSAGE PREPARATION: the test substance was diluted to the appropriate concentration in the vehicle.
Doses:
2000 mg/ kg bw
No. of animals per sex per dose:
6 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All surviving animals were observed for a period of 14 days.
During the follow-up period of two weeks, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Observations on deaths were made at least once daily to minimize loss of animals during the study. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded.
- Necropsy of survivors performed: yes
At the end of the experiments, all animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded. Autopsy and macroscopic inspection of animals which died prematurely would have been carried out as soon as possible after exitus.
Histopathology was not carried out as no macroscopical findings were noted at autopsy.


Statistics:
No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: mortality: 0/6, no signs of toxicity
Mortality:
No death was recorded within the test period.
Clinical signs:
Under the present test conditions, a single oral administration of 2000 mg octanoic acid, zinc salt, basic/kg bw to female rats did not reveal any signs of toxicity.
Body weight:
All animals gained the expected weight throughout the whole study period.
Gross pathology:
No pathological changes were observed at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 (female rats) > 2000 mg/kg b.w.
According to the EC-Regulation 1272/2008, the test item is not classified as acute toxic via the oral route.


Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-04-24 to 2012-05-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Fatty acids, C8 -10, zinc salts is a zinc salt of a short-chained fatty acids containing 8 -10 C-atoms. Thus, read-across of data available for zinc salts of short-chained (C8, C12) and longr-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 fatty acids, C8 -10, zinc salts. Acute toxicity is addressed with data read-across from relevant zinc soaps (zinc salts of short-chained (C8, C12) and long-chained (C16 -18) fatty acids), including (i) octanoic acid, zinc salt, basic (C8), (ii) zinc dilaurate,(iii) zinc bis[12 -hydroxy-octadecanoate, and (iv) Fatty acids, C16-18, zinc salts,as well as supporting information from slightly soluble/insoluble zinc compounds.

Regarding the potential for inhalation toxicity, fatty acids, C8 -10, zinc salts was tested to determine the potential of the dust to be airborne (modified Heubach procedure (DIN 55992-1:2006)), yielding an MMAD of 21.66 µm with a GSD of 1.96. On the basis of this dustiness test (modified Heubach method), a MPPD modelling was performed and shows that only minimal amounts of the substance are able to penetrate to the deep lung tissues (tracheobronchial: 0.3%; pulmonary: 0.3%), whereas the overwhelming bulk (head: 59.1%) of inhaled material is cleared rapidly to the GI tract (by swallowing), where oral bioavailability will determine its uptake. Based on MMAD and MMPD modelling of fatty acids, C8 -10, zinc salts, the absence of a respiration risk is conceivable. Furthermore, different reliable studies conducted with different zinc compounds are read-across to address the endpoint acute inhalation toxicity, including (i) zinc oxide; and (ii) Fatty acids, C16-C18, zinc salts; and (iii) zinc dilaurate. Due to its particle size distribution, zinc dilaurate - the test item of the selected key study - potentially reaches in substantial higher amounts than substance Fatty acids, C8-10, zinc salts the deep respiratory tract and thus, represents a worst case read-across structural analog. Based on the absence of a respiration risk as well as the whole toxicity data base, fatty acids, C8 -10, zinc salts is not expected to be acutely toxic via the inhalation route. Reported LC50s of structural analogues (i.e. short- and long chained zinc salts of fatty acids) are magnitudes higher than the value reported for metal fume fever. In sum, metal fume fever is not relevant for zinc salts of fatty acids. In conclusion, testing for acute toxicity of fatty acids, C8-10, zinc salts via the inhalation route is not required according the criteria laid down in Regulation (EC) 1907/2006 Annex VIII, 8.5, column 2.
Qualifier:
according to guideline
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Version / remarks:
adopted September 7, 2009
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: OECD Series on Testing and Assessment No. 125, Document No. ENV/JM/MONO (2010) 16, June 01, 2010.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2009-11-12
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: males: 7 weeks; females: 9 weeks
- Weight at study initiation: males: 242 - 256 g; females: 217 - 240 g
- Fasting period before study: feeding was discontinued approx. 16 hours before exposure; only tap water was then available ad libitum.
- Housing: granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages. During the 14-day observation period, the animals are kept by sex in groups of 2 - 3 animals in MAKROLON cages (type III plus).
- Diet (e.g. ad libitum): commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum): drinking water
- Acclimation period: at least 5 adaptation days

The animals were randomised before use. They were acclimatised to the test apparatus for approx. 1 hour on 2 days prior to testing. The restraining tubes did not impose undue physical, thermal or immobilization stress on the animals.

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C (maximum range)
- Relative humidity: 55% ± 15% (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: the study was carried out using a dynamic inhalation apparatus (RHEMA-LABORTECHNIK, 65719 Hofheim/Taunus, Germany) (air changes/h (≥ 12 times)) with a nose-only exposure of the animals according to KIMMERLE & TEPPER. The apparatus consists of a cylindrical exposure chamber (volume 40 L) which holds 10 animals in pyrex tubes at the edge of the chamber in a radial position.

- System of generating particulates/aerosols: the dust of the test material was generated with a rotating brush dust generator (RBG 1000, PALAS GmbH Partikel und Lasermesstechnik,76229 Karlsruhe, Germany).
The generator was fed with compressed air (5.0 bar) from a compressor (ALUP Kompressorenfabrik, 73257 Köngen, Germany) (air was taken from the surrounding atmosphere of the laboratory room and filtered using at in-line disposable gas-filter).
At the bottom of the exposure chamber, the air was sucked off at a lower flow rate than it was created by the dust generator in order to produce a homogenous distribution and a positive pressure in the exposure chamber (inflow 900 L/h, outflow 800 L/h).
A manometer and an air-flow meter (ROTA Yokogawa GmbH & Co. KG, 79664 Wehr/Baden, Germany) were used to control the constant supply of compressed air and the exhaust, respectively. Flow rates were checked hourly and the corrected if necessary.
The exhaust air was drawn through gas wash-bottles.

- Method of particle size determination: an analysis of the particle size distribution was carried out twice during the exposure period using a cascade impactor according to MAY (MAY, K. R. Aerosol impaction jets, J. Aerosol Sci. 6, 403 (1975), RESEARCH ENGINEERS Ltd., London N1 5RD, UK.).
The dust from the exposure chamber was drawn through the cascade impactor for 5 minutes at a constant flow rate of 5 L/min. The slides were removed from the impactor and weighed on an analytical balance (SARTORIUS, type 1601 004, precision 0.1 mg). Deltas of slides’ weight were determined.
The mass median aerodynamic diameter (MMAD) was estimated by means of non-linear regression analysis. The 32 μm particle size range and the filter (particle size range < 0.5 μm) were not included in the determination of the MMAD in order not to give undue weight to these values.
The Geometric Standard Deviation (GSD) of the MMAD was calculated from the quotient of the 84.1%- and the 50%-mass fractions, both obtained from the above mentioned non-linear regression analysis.
In addition, a sample of approx. 10 g test material was taken from the exposure chamber to determine the median physical particle size with a CILAS 715 by My-Tec, 91325 Adelsdorf, Germany. This determination was non-GLP.

- Temperature, humidity, pressure in air chamber, oxygen content and carbon dioxide concentration: the oxygen content in the inhalation chamber was 21%. It was determined at the beginning and at the end of the exposure with a DRÄGER Oxygen-analysis test set (DRÄGER Tube Oxygen 67 28 081). Carbon dioxide concentration did not exceed 1%.
Temperature (22.5°C ± 0.4°C (main study) or 20.5°C ± 0.1°C (satellite group)) and humidity (61.9% ± 0.9% (main study) or 66.8% ± 0.1% (satellite group)) were measured once every hour with a climate control monitor (testo 175-HZ data logger).

The whole exposure system was mounted in an inhalation facility to protect the laboratory staff from possible hazards.

Exposition started by locating the animals into the exposure chamber after equilibration of the chamber concentration for at least 15 minutes (t95 approximately 8 minutes).

Before initiating the study with the animals, a pre-test was carried out with the exposure system in order to verify that under the experimental settings chosen, the limit concentration of 5 mg/L air could be achieved by gravimetric analysis.

The tests with the main study animals and the recovery animals were conducted in the same inhalation chamber but on different days. Between the exposure times the chamber was cleaned carefully.

TEST ATMOSPHERE
- Brief description of analytical method used: the actual dust concentration in the inhalation chamber was measured gravimetrically with an air sample filter (Minisart SM 17598 0.45 μm) and pump (Vacuubrand, MZ 2C (Membrane Pump,Vacuubrand GmbH + Co. KG, 97877 Wertheim/Main, Germany)) controlled by a rotameter. Dust samples were taken once every hour during the exposure. For that purpose, a probe was placed close to the animals' noses and air was drawn through the air sample filter at a constant flow of air of 5 L/min for 1 minute. The filters were weighed before and after sampling (accuracy 0.1 mg).
Individual chamber concentration samples did not deviate from the mean chamber concentration by more than 1%.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
Main study: 1.953 µm (GSD: 2.94)
Satellite group: 2.037 µm (GSD: 3.06)
No smaller GSDs could be obtained with the test item supplied.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
see above ("Details on inhalation exposure")
Duration of exposure:
4 h
Concentrations:
Main study (limit test):
- actual concentration: 5.08 ± 0.03 mg/L air
- nominal concentration: 6.67 mg/L air
Satellite group:
- actual concentration: 5.05 ± 0.04 mg/L air
- nominal concentration: 6.67 mg/L air
No. of animals per sex per dose:
Main study (limit test):
3 males / 3 females
Satellite group:
3 males / 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 24 hours (satellite group) and 14 days (main study)

- Frequency of observations and weighing: during and following exposure, observations were made and recorded systematically; individual records were maintained for each animal. Careful clinical examinations were made at least once daily until all symptoms subsided, thereafter each working day. Observations on mortality were made at least once daily (in the morning starting on test day 2) to minimize loss of animals to the study, e.g. necropsy or refrigeration of those animals found dead and isolation or sacrifice of weak or moribund animals.
Cageside observations included, but were not limited to: changes in the skin and fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, as well as somatomotor activity and behaviour pattern.
Particular attention was directed to observation of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma. The animals were also observed for possible indications of respiratory irritation such as dyspnoea, rhinitis etc.
Individual weights of animals were determined once during the acclimatisation period, before and after the exposure on test day 1, on test days 3, 8 and 15. Changes in weight were calculated and recorded when survival exceeded one day. At the end of the test, all animals were weighed and sacrificed.

- Necropsy of survivors performed: yes
Necropsy of all main study and satellite animals (3 + 3 males and 3+3 females) was carried out and all gross pathological changes were recorded:
- Satellite animals: necropsy at 24 hours after cessation of exposure, as this is likely to be the time at which any signs of respiratory irritation would have manifested;
- Main study animals: necropsy at the end of the 14-day observation period, also to assess whether any respiratory tract irritation persists or abates.

- Histopathology:
All main study and satellite animals were subjected to the same level of histopathological examination upon necropsy at the end of the respective observation period. During histopathology, attention was paid to alterations that might be indicative of respiratory irritation, such as hyperaemia, oedema, minimal inflammation, thickened mucous layer.
The following organs of all animals were fixed in 10% (nose, i.e. head without brain, eyes and lower jaw) or 7% (other organs) buffered formalin for histopathological examination:
- Nasal cavity, nasopharynx and paranasal sinus:
The tip and level 1 of the nose were taken from a cut just anterior to the incisor teeth. With tip removed, level 2 was taken approximately 2 mm posterior to free tip of the incisor teeth. Level 3 was cut through the incisive papilla. Level 4 was cut through the middle of the second palatal ridge, which is located just anterior to the molar teeth. Level 5 was cut through the middle of the molar teeth. All sections were embedded face down to yield a section from the anterior section, except the nose tip was embedded posterior surface down.
- Larynx
- Trachea
- Lungs (five levels)
Paraffin sections were prepared of all above mentioned organs and stained with haematoxylin-eosin.
Statistics:
Since no animal died prematurely, the calculation of an LC50 was not required.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.08 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: mortality: 0/10; temporary slight clinical signs attributed to inert dust exposure, no clinical signs of substance specific irritation, macroscopic findings (marbled lungs associated with small black foci) without histopathological correlation
Mortality:
No animal died prematurely.
Clinical signs:
other: Under the present test conditions, a 4-hour inhalation exposure to zinc dilaurate at a concentration of 5.08 mg/L air revealed slightly reduced motility, slight ataxia and slightly reduced muscle tone on test day 1 immediately after the end of exposure un
Body weight:
No influence on body weight gain was observed.
Gross pathology:
Macroscopic changes in the nasal cavity and lungs. Marbled lungs were observed in all animals of the main study (14-day sacrifice) and in all satellite animals (24-hour sacrifice). Small black foci were observed in 2 of 3 male and 1 of 3 female satellite animals.
Other findings:
- HISTOPATHOLOGY
Microscopic changes in the nasal cavity and lungs:
1. Test item-related histopathological changes: the histomorphological examination of the trachea, larynx, lungs and the nose of male and female rats after inhalation of zinc dilaurate did not reveal any morphological changes, considered to be related to the inhalation of the test item, in the main study animals and in the satellite animals.
2. Non-test item-related histopathological changes:
Male and female animals of the main study and the satellite group:
- Observations made for the nose (five levels): the nasal cavity of level 1 showed a normal squamous epithelium and a normal respiratory epithelium with goblet cells. A mild congestion was noted in all animals.
The level 2 and 3 showed a similar normal morphological finding with congestion compared to level 1.
The normal respiratory epithelium partially with cilia contained three major cell types, the basal cells above the basement membrane, the ciliated epithelial cells and the secretory goblet cells.
A normal olfactory epithelium with 5 to 7 nuclear layers, normal basal cells, olfactory sensory cells and sustentacular cells was noted in the male and female animals.
The level 4 and 5 of the nose showed focally an olfactory epithelium with mild vacuolization and a loss of epithelial cells (artefacts) on the nasal surface in the dorsal region of the nasal cavity. A normal olfactory epithelium was noted in the other region of the nasal cavity.
Minimal to mild lympho-histiocytic infiltrations or follicular lymphoid hyperplasia in the subepithelial region of the respiratory epithelium (naso-pharynx region) was observed as a normal finding.
- Observations made for the lungs (five levels): the most localisations of the lungs in the main study (14-day sacrifice) and in the satellite group (24-hour sacrifice) were morphologically normal without pathological findings.
Some localisations showed minimal to mild alveolar pulmonary emphysema and mild congestion. In some animals a focal haemorrhage was observed.
The larynx showed in some rats a minimal subepithelial lympho-histiocytic infiltration.
In the trachea some animals showed a focal mild lympho-histiocytic infiltration or a tracheal gland dilatation.
Only in 7 from 30 lung localisations a focal minimal inflammatory oedema with few lymphocytes and neutrophilic granulocytes and a mild congestion was observed.
Interpretation of results:
GHS criteria not met
Conclusions:
LC50 (rats; 4 hours) > 5.08 mg/L air (actual concentration)
Based on the results of the histopathological and macroscopic investigations, zinc dilaurate does not require classification for respiratory irritation.
According to the EC-Regulation 1272/2008, the test item is not classified as acute toxic via the inhalation route or as specific target organ toxicity - single exposure.
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Fatty acids, C8-10, zinc salts

No acute toxicity studies with Fatty acids, C8-10, zinc salts are available, thus the acute toxicity will be addressed with existing data on the dissociation products zinc and fatty acids, C8-10 and with existing data on structurally similar zinc salts of fatty acids.

 

Acute oral toxicity

Regarding acute oral toxicity, a reliable GLP study conducted with octanoic acid, zinc salt, basic (C8) is read-across to address this endpoint.

Different reliable studies conducted with different zinc compounds are read-across as supporting information, including (i) zinc oxide; (ii) Fatty acids, C16-C18, zinc salts; (iii) zinc bis [12-hydroxy-octadecanoate]. Based on the lack of an acute toxicity potential of a zinc salt of a similar chained (C8) fatty acid and zinc salts of longer-chained (C16 -18) fatty acids and slightly soluble/insoluble zinc substances, the LD50 for fatty acids, C8 -10, zinc salts was estimated to be greater than 2000 mg/kg bw.

 

Acute inhalation toxicity

Regarding the potential for inhalation toxicity, fatty acids, C8 -10, zinc salts was tested to determine the potential of the dust to be airborne (modified Heubach procedure (DIN 55992-1:2006)), yielding an MMAD of 21.66 µm with a GSD of 1.96. On the basis of this dustiness test (modified Heubach method), a MPPD modelling was performed and shows that only minimal amounts of the substance are able to penetrate to the deep lung tissues (tracheobronchial: 0.3%; pulmonary: 0.3%), whereas the overwhelming bulk (head: 59.1%) of inhaled material is cleared rapidly to the GI tract (by swallowing), where oral bioavailability will determine its uptake. Based on MMAD and MMPD modelling of fatty acids, C8 -10, zinc salts, the absence of a respiration risk is conceivable. Furthermore, different reliable studies conducted with different zinc compounds are read-across to address the endpoint acute inhalation toxicity, including (i) zinc oxide; and (ii) Fatty acids, C16-C18, zinc salts; and (iii) zinc dilaurate. Due to its particle size distribution, zinc dilaurate - the test item of the selected key study - potentially reaches in substantial higher amounts than substance Fatty acids, C8-10, zinc salts the deep respiratory tract and thus, represents a worst case read-across structural analogue. Based on the absence of a respiration risk as well as the whole toxicity data base, fatty acids, C8 -10, zinc salts is not expected to be acutely toxic via the inhalation route. Reported LC50s of structural analogues (i.e. short- and long chained zinc salts of fatty acids) are magnitudes higher than the value reported for metal fume fever. In sum, metal fume fever is not relevant for zinc salts of fatty acids.

 

Acute dermal toxicity

Regarding acute dermal toxicity, a study is not available. However, following the HERAG guidance for metals and metal salts (see section 7.1.2 of the technical dossier: dermal absorption), negligible percutaneous uptake based on minimal penetration, i.e. a dermal absorption rate in the range of maximally 0.1 - 1.0 %, can be anticipated. Dermal absorption in this order of magnitude is not considered to be “significant”. Furthermore, the LD50 of Fatty acids, C16-18, zinc salts has been estimated to be greater than 2000 mg/kg bw. Based on the assumption that zinc compounds with similar solubility characteristics can be read-across, it is concluded that other slightly soluble and insoluble zinc compounds are also expected to be not acutely toxic. This conclusion is applied to fatty acids, C8 -10, zinc salts. In conclusion, testing for acute toxicity of fatty acids, C8 -10 zinc salts via the dermal route is not required according the criteria laid down in Regulation (EC) 1907/2006, Annex VIII, point 8.5.

The oral, inhalation and dermal LD50 for fatty acids, C8-10, zinc salts is > 2000mg/kg, hence the substance is not to be classified according to regulation (EC) 1272/2008 for acute oral, inhalation and dermal toxicity as well as for specific target organ toxicity, single exposure (STOT SE). Further testing is not required.

This conclusion is in line with the EU risk assessment carried out on the structural analogue substance Fatty acids, C16-18, zinc salts (i.e. zinc stearate) within the framework of EU Existing Chemicals Regulation 793/93 (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): "Zinc distearate does not need to be classified on the basis of its acute toxicity according to the EC criteria." A similar lack of acute toxicity is considered for substance Fatty acids, C8-10, zinc salts.

Please refer to the respective assessment entity section for data on the moieties zinc and fatty acids C8-10. In brief:

Zinc

 

Acute oral toxicity

With LD50values consistently exceeding 2,000 mg/kg bw, zinc oxide (LD50ranges between 5,000 and 15,000mg/kg bw), shows very low level of acute oral toxicity.

Acute inhalation toxicity

Key study carried out according to OECD guideline no 403 indicating for micro zinc oxide LC50 > 5.7 mg/L/4hrs

Acute dermal toxicity

There are no available data on which to evaluate acute dermal toxicity for ZnO micromaterial. However, acute dermal toxicity can be considered to be low taking into account the poor percutaneous absorption of zinc oxide or the zinc cation.

Fatty acids, C8-10

 

Acute oral toxicity

Fatty acids, C8 -10 is a mixture of the naturally occurring even numbered saturated fatty acids caprylic and capric acid. Caprylic and capric acid are present in milk of various mammals and also in coconut oil and palm kernel oil. Based on this, the following endpoint is covered by publicly available data on fatty acids with the same or similar structure.

According to the HERA document on fatty acid salts (2002) “the available data for fatty acids provide a clear picture of low acute toxicity for this class of chemicals. All oral LD50values were greater than 2,000 mg/kg, with little mortality being observed even at the highest doses tested in the studies (IUCLID, 2000c, 2000e, 2000f, 2000g; Clayton & Clayton, 1982; CIR, 1987)” (HERA, 2002).

Based on in vivo data it was reported that “in an OECD TG 401 study, a group of five rats/sex was administered octanoic acid at a dose of 2000 mg/kg bw. There were no deaths, clinical signs, or findings at gross necropsy. The LD50was > 2000 mg/kg bw”(OECD SIDS, 2014).

“Smyth et al. (1962) studied the acute oral toxicity of undiluted caprylic- or capric acid (mixed isomers tested) in groups of five non-fasted male Carworth–Wistar rats. Based upon mortalities during the 14-day observation period, the authors reported median lethal dose (LD50) values of 1,300 mg/kg bw for caprylic acid and 3,300 mg/kg bw for capric acid (no further details available). Jenner et al. (1964) administered, by gavage, increasing doses of octanoic acid to groups of five male and five female fasted Osborn–Mendel rats (dose range 8,190–12,370 mg/kg bw). The treated rats showed depression and diarrhoea during the 2-week observation period. The rats died between 4 h and 9 days after application. The authors calculated a LD50 of 10,080 mg/kg bw for male and female rats (no further details given)” (EFSA ANS Panel, 2017).

 

Acute dermal toxicity

Fatty acids, C8 -10 is a mixture of the naturally occurring saturated fatty acids caprylic and capric acid. Caprylic and capric acid are present in milk of various mammals and also in coconut oil and palm kernel oil. Based on this, the following endpoint is covered by publicly available data on fatty acids with the same or similar structure.

The HERA document on fatty acids salts concluded that “the available acute dermal toxicity data for the fatty acids (and their salts) provide a clear picture of low acute toxicity for this group of chemicals. All dermal LD50values were greater than 2,000 mg/kg (BIBRA, 1996; IUCLID, 2000e; Clayton & Clayton, 1982; CIR, 1982, 1987).

In a series of studies performed by the British Industrial Biological Research Association (BIBRA, UK), the acute dermal toxicity of octanoic acid was evaluated in rats. In these studies, octanoic acid was found to have a very low acute dermal toxicity in rats. The established LD50 was higher than 5,000 mg/kg bw (BIBRA, 1996).

In a dermal study in which concentrations of sodium stearate (C18) ranged between 10-25% in a 20% bath soap detergent form, the LD50was >3000 mg/kg (highest dose tested) (CIR, 1982). In a dermal study in guinea pigs, application of commercial grade oleic acid (3,000 mg/kg) produced no deaths and no signs of toxicity. The number of applications was not stated (CIR, 1987)” (HERA, 2002).

 

Justification for classification or non-classification

The oral and dermal LD50 for Fatty acids, C8-10, zinc salts is > 2000mg/kg, hence the substance is not to be classified according to regulation (EC) 1272/2008 for acute oral and dermal toxicity as well as for specific target organ toxicity, single exposure (STOT SE).

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