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Administrative data

Description of key information

The slightly soluble and insoluble zinc compounds (i.e., zinc oxide, zinc hydroxide,  zinc phosphate, zinc carbonate, zinc metal, zinc sulphide as well as zinc bis[12-hydroxyoctadecanoate]) are of low acute, dermal and inhalation toxicity not requiring a classification for acute toxicity.

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:
2002-02-19 to 2002-03-06
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study. Signed translation of an original well documented report.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 1996-03-22
GLP compliance:
not specified
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Gartenstrße 27, D- 33178 Borchen, Germany
- Weight at study initiation:mean weight males: 217.7 g; mean weight females: 208 g
- Fasting period before study: Food was withheld overnight before the day of administration. Food was withheld for further 4 hours after administration.
- Housing: The rats housed individually in Makrolon cages (area 800 cm^2, height 19 cm) with bedding
- Diet: Haltungsdiät "ALMA 0813 A H 1003", 8 g twice daily (Manufacturer: Meika Kraftfutter)
- Water (ad libitum): Community tap water of the city of Karlsruhe; daily changing of watering bottles
- Acclimation period: After randomization the animals were acclimated to the test conditions for 5 days prior to administration.
- Veterinary preliminary examination: Animals without morbid signs; females are nulliparous and non-pregnant

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 24 °C
- Relative humidity: 30 -70 %
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
Calculated amounts of "Zinc 12-hydroxystearate" according to the dosage of 2000 mg/kg bw were administered with the aid of a stomach tube to rats.

VEHICLE: Sesame oil
- Batch no. : 36834458 (Carl Roth GmbH & Co.)

DOSAGE PREPARATION: Weighed amounts of "Zinc 12-hydroxystearate" were dissolved in 2 ml sesame oil immediatly before administration.

No further information on the oral exposure was stated.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
3 males / 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Necropsy of survivors performed: Yes, at the end of the observation period. The anaesthesia and euthanasia of all surviving animals were performed in an atmosphere of approx. 80 % CO2 at the end of the observation period.
- Examinations performed: Mortality, body weight (daily, except day 5 and day 12), behaviour, and toxicological symptoms (daily, except day 5 and day 12)(The criteria of judgement were changes of the fur, of the skin, the nose and the mouth and their mucus membranes eyes, anal region, faeces, urine (macroscopically), breathing, circulatory, and nervous system)
No further information on the study design was stated.
Statistics:
not stated
Sex:
male/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:
After oral application of 2000 mg "Zinc 12-hydroxystearate" per kg body weight none of the 6 tested animals died during the observation period of 15 days.
Clinical signs:
No toxicological symptoms were observed.
Body weight:
An increase in body weight was observed.
Gross pathology:
No pathological findings were noted.
Other findings:
no data
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
"Zinc 12-hydroxystearate" has a LD50 (male and female rats) > 2000 mg/kg bw.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as acute toxic via the oral route.
According to the Regulation (EC) No. 1272/2008 and subsequent regulations, 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
Quality of whole database:
Adequate and relevant guideline studies RL2

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was peer-reviewed and rated reliable within the framework of the 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). In accordance with Section 1 (0.5), Annex I of Regulation (EC) No 1907/2006 (REACH), this study was considered reliable with restrictions.
Reason / purpose for cross-reference:
reference to same study
Principles of method if other than guideline:
A single 1-hr exposure of rats to 200 mg/L zinc stearate. The rats were observed for two weeks.
GLP compliance:
no
Test type:
other: not stated
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
Albino rats were used.
No further information on the test animals was stated.
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
not specified
Details on inhalation exposure:
Rats were exposed to zinc stearate for one hour.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
1 h
Concentrations:
200 mg/l zinc stearate (Chamber concentration)
No. of animals per sex per dose:
10 rats
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Examinations performed: moratlity was reported.
No further information on the study design was stated.
Statistics:
not stated
Sex:
not specified
Dose descriptor:
LC50
Effect level:
> 200 other: mg/L
Based on:
test mat.
Exp. duration:
1 h
Sex:
not specified
Dose descriptor:
LC50
Effect level:
> 50 other: mg/L
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: mortality: 1/10 rats; al animals appeared depressed for the first 6 hrs.. This LC50 was recalculated from the LC50 (1 hr) by using Haber's law.
Mortality:
1/10 rats died during the 2-week observation period.
Clinical signs:
other: All animals appeared depressed for the first six hours. From 24 hrs. until day 14, they appeared normal.
Body weight:
not stated
Gross pathology:
not stated
Other findings:
not stated
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LC50 (4 h) > 50 mg/l (recalculated from LC50 (1h) by using Haber's law)
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as acute toxic via the inhalation route.
According to the Regulation (EC) No. 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the inhalation route.

This conclusion is in accordance with the conclusion of the 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."
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
50 000 mg/m³
Quality of whole database:
Adequate and relevant data RL2

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

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 (C8,12) 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]. Acute toxicity is addressed with substance-specific information and data 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. Thus, read-across of toxicological data of (i) zinc oxide; (ii) octanoic acid, zinc salt, basic; (iii) zinc dilaurate; and (iv) Fatty acids, C16-18, zinc salts is applied to zinc bis[12-hydroxyoctadecanoate. Regarding acute oral toxicity, substance specific data as well as read-across data from different reliable studies conducted with (i) zinc oxide; (ii) Fatty acids, C16-18, zinc salts; and (iii) octanoic acid, zinc salt, basic are addressed. The LD50 for zinc bis[12-hydroxyoctadecanoate] was estimated to be greater than 2000 mg/kg bw. Regarding acute inhalative toxicity, different reliable studies conducted with different zinc compounds are read-across to address this endpoint, including (i) zinc oxide; (ii) Fatty acids, C16-C18, zinc salts; and (iii) zinc dilaurate. Based on the lack of an acute inhalative toxicity potential of zinc salts of similar chained (C16-18) and shorter-chained (C12) fatty acids, a similar lack of acute inhalative toxicity is considered for zinc bis[12-hydroxyoctadecanoate]. The LC50 for Fatty acids, C16 -18, zinc salts was estimated to be greater than 50 mg/L and is thus magnitudes higher than the value reported for metal fume fever. A similar conclusion can be drawn for the structural analogue zinc dilaurate for which a LC50 of greater than 5.08 mg/L (actual concentration) was determined. In sum, metal fume fever is not relevant for zinc salts of fatty acids at all. 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. In sum, acute oral and dermal LD50values exceed 2,000 mg/kg bw.

 

The read-across to "Zinc", based on the assumption that after intake zinc bis[12-hydroxyoctadecanoate] is changed (at least in part) to ionic zinc and that only ionic zinc is determining biological activities results in similar or higher effect levels except for inhalation. The LC50 for acute inhalation toxicity of Fatty acids, C16 -18, zinc salts being 50 mg/L ist about 3 magnitudes higher than the value reported for metal fume fever. However, metal fume fever is not relevant for zinc bis[12-hydroxyoctadecanoate].

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): "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 zinc bis[12-hydroxyoctadecanoate].

Conclusions: Based on substance-specific data and applying read-across, zinc bis[12-hydroxyoctadecanoate] does not need to be classified on the basis of its acute toxicity.

ZINC:

With LD50values consistently exceeding 2,000 mg/kg bw, slightly soluble or insoluble zinc compounds such as zinc oxide (LD50ranges between 5,000 and 15,000mg/kg bw), zinc phosphate (LD50is >5,000mg/kg bw), zinc metal (LD50 >2,000mg/kg bw) or zinc sulphide (LD50is >15,000mg/kg bw), show level of acute oral toxicity. Moreover, zinc oxide and zinc metal were further shown to be of low acute inhalation toxicity (i.e., LC50 values of > 5.41 and 5.7 mg/L/4hrs). Given the common characteristics shared via their solubility characteristics, the remaining slightly soluble zinc compounds are also considered to be of low acute inhalation toxicity.

Of significance for humans from an acute toxicity standpoint is the occurrence of metal fume fever following exposure to ultrafine particles of special grades of zinc oxide in context of very specific operations. According to the response from 11 zinc companies to a questionnaire, there have been no observations of zinc metal fume fever over the last decade and in recent occupational practice. However in light of responsible care and since no studies are available that allow the establishment of a NOAEL for metal fume fever with a reasonable degree of certainty, a LOAEL (5 mg ZnO/m3) for 2 hours (showed the typical metal fume fever symptoms beginning 4 to 8 hours after exposure and disappearing within 24 hours) can be used for metal fume fever based on the study by Gordon et al.(1992).

References:

[EU RAR Zinc distearate (CAS-No.: 557-05-1 & 91051-01-3 EINECS-No.: 209-151-9 & 293-049-4) Part II - Human Health (Final report, May 2008;http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1)]

[Gordon T, Chen LC, Fine JM, Schlesinger RB, Su WY, Kimmel TA and Amdur MO (1992). Pulmonary effects of inhaled zinc oxide in human subjects, guinea pigs, rats, and rabbits. Am Ind Hyg Assoc J 53(8): 503-509.]


Justification for selection of acute toxicity – oral endpoint
One reliable study with zinc bis[12-hydroxyoctadecanoate] is available. Different reliable, relevant and adequate studies conducted with different zinc compounds are read-across as supporting information, including (i) zinc oxide; (ii) Fatty acids, C16-18, zinc salts; and (iii) octanoic acid, zinc salt, basic. It is assumed that after intake substance zinc bis[12-hydroxyoctadecanoate] is changed (at least in part) to ionic zinc and that only ionic zinc is determining biological activities. The toxic potential of the fatty acid chain, i.e. 12-hydroxystearate, is assumed to be negligible. Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)). The lowest discriminating dose was selected for the CSA. Based on the whole data base, the LD50 of zinc bis[12-hydroxyoctadecanoate] is estimated to be greater than 2000 mg/kg bw.

Justification for selection of acute toxicity – inhalation endpoint
Based on similar structural analogy, water solubility and zinc content of zinc bis[12-hydroxyoctadecanoate] (CAS 35674-68-1) and Fatty acids, C16-18, zinc salts (CAS 91051-01-3), a 1:1 read-across of toxicological data of Fatty acids, C16-18, zinc salts is applied to zinc bis[12-hydroxyoctadecanoate]. One reliable, relevant and adequate study conducted with Fatty acids, C16-18, zinc salts (CAS 91051-01-3) is read-across to address this endpoint. Different reliable, relevant and adequate studies conducted with different zinc compounds are read-across as supporting information, including (i) zinc oxide; and (iii) zinc dilaurate. It is assumed that after intake substance zinc bis[12-hydroxyoctadecanoate] is changed (at least in part) to ionic zinc and that only ionic zinc is determining biological activities. The toxic potential of the fatty acid chain, i.e. 12-hydroxystearate, is assumed to be negligible. Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)). Based on the whole data base and specifically the key study, the LC50 for zinc bis[12-hydroxyoctadecanoate] is estimated to be greater than 50 mg/L (recalculated from 1 hour exposure with rats using Haber's law).

Justification for selection of acute toxicity – dermal endpoint
Derogation according the criteria laid down in Regulation (EC) 1907/2006 Annex VIII, 8.5, column 2.

Justification for classification or non-classification

The slightly soluble/insoluble zinc compounds (i. e., zinc oxide, zinc hydroxide, zinc phosphate, zinc carbonate, zinc metal, zinc sulphide as well as zinc bis[12-hydroxyoctadecanoate]) are of low acute toxicity.

According to Directive 67/548 EEC and CLP Regulation (EC) No 1272/2008, a classification and labelling for acute toxicity of zinc bis[12-hydroxyoctadecanoate] is not required.

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