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Description of key information

No acute toxicity studies with zinc didocosanoate are available, thus the acute toxicity will be addressed with existing data on the dissociation products zinc and docosanoic acid. Signs of acute oral toxicity are not expected for zinc ditetradecanoate, since for the moieties zinc and tetradecanoate have not shown signs of acute oral toxicity (LD50 > 2000mg/kg).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Used in EU risk assessment for zinc oxide, limited study details provided
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
5 per sex
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
single dose by oral gavage in water and observed for 14 days
Doses:
single dose of 5 gZnO/kg bw
No. of animals per sex per dose:
5 per sex
Control animals:
not specified
Details on study design:
no further information
Statistics:
no data
Preliminary study:
no further information
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
no mortality
Clinical signs:
no adverse signs of toxicity
Body weight:
no adverse signs of toxicity
Gross pathology:
no adverse signs of toxicity

none

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 > 5000 mg ZnO/kg bw was determined.
Executive summary:

In an acute toxicity test Wistar rats (5/sex) were given a single dose of 5 g ZnO/kg bw (in water) by gavage and observed for 14 days. No mortality and signs of toxicity were observed. The LD50for rats is therefore >5 g ZnO/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is well documented and meets general acceptable scientific principle.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
not specified
Remarks:
the publication does not specify GLP compliance
Test type:
other: limit test
Limit test:
yes
Species:
mouse
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
No data
Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
- Rationale for the selection of the starting dose: Based on the result of another study (Yamaki & Yoshino 2009).
Doses:
5,000 mg/kg bw for both ZnO nanoparticle and microparticle
No. of animals per sex per dose:
5/sex/dose
Control animals:
yes
Details on study design:
Thirty mice were divided into three groups (five males and five females per group). Mice were fed with vehicle (control group), 5,000 mg/kg bw ZnO-nanoparticle suspension or 5,000 mg/kg bw ZnO-microparticles suspension. Dosed mice were conditioned for 14 d. The mortality and clinical behaviour were observed daily. Body weights were recorded twice weekly. At the end of the study (on Day 14), the mice were anaesthetised with isoflurane and blood (for serum biochemistry analysis) was collected from the orbital sinus, followed by gross necropsy. Tissue samples (for histopathologic examination) were taken and fixed in 10% neutral buffered formalin
Statistics:
All data were expressed as the mean ± SD from at least three independent experiments (N ‡ 3). The significance of the difference between the control and each experimental test condition was analysed by Student’s t-test. Statistically significant differences among groups were determined using one-way analysis of variance (ANOVA). A value of p < 0.05 was taken as statistically significant.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
Not observed
Clinical signs:
Not observed
Body weight:
In comparison with vehicle control group, ZnO microparticles treated group showed a body weight reduction in both males (Days 5 and 10) and females (Days 5, 10, and 14); the body weight changes were unobvious in ZnO nanoparticle treated groups.
Gross pathology:
Decreased wet weights of the spleen, kidney, and liver were observed in ZnO microparticles treated females but not in ZnO nanoparticle treated males. However, no obvious gross pathological signs were found in the study.
Other findings:
All serum biochemistry measures were without any significant alternation except for marginal variations in certain parameters.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the study details, the LD50 value of both the ZnO nanoparticles and ZnO microparticles can be established at >5,000 mg/kg bw in mice.
Executive summary:

The study was conducted to examine the acute toxicity of both ZnO nanoparticles and ZnO microparticles in mice.

Thirty mice were divided into three groups (five males and five females per group). Mice were fed with vehicle (control group), 5,000 mg/kg bw ZnO-nanoparticle suspension or 5,000 mg/kg bw ZnO-microparticles suspension. Dosed mice were conditioned for 14 d.

All the mice survived throughout the testing period without exhibiting any abnormalities related to the test substances. In comparison with the vehicle control group, ZnO-microparticles treated group showed a body weight reduction in both males (Days 5 and 10) and females (Days 5, 10, and 14); the body weight changes were not obvious in ZnO-nanoparticle treated groups. All serum biochemistry measures were without any significant alterations except for marginal variations in certain parameters.

Based on the study details, the LD50 value of both the ZnO nanoparticles and ZnO microparticles can be established at >5,000 mg/kg bw in mice.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: According to the OECD guideline, but mice used
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
mouse
Strain:
other: CD-ICR
Sex:
male/female
Details on test animals or test system and environmental conditions:
Age: 8 weeks
Weight: 20-22 g
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Doses:
1000, 2000, 3000, 4000, 5000 mg/kg
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:before begin of study, after 2 and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology, blood analysis
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: 20 nm ZnO
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 - < 5 000 mg/kg bw
Remarks on result:
other: 120 nm ZnO
Mortality:
One female death occurred in the nano-scale 2000 mg group and one male death in the nano-scale 5000 mg group.
As for 120-nm ZnO treated mice, one and three female mice died in the sub-micro 2000 mg and 5000 mg group.

Combined with the results of zinc accumulation, pathological examination and the biological indicators assays, according to the authors the target organs for 20- and 120-nm ZnO acute oral administration are demonstrated as liver, heart, spleen, pancreas and bone.

The biochemical and pathological investigation shows that the toxic effects between the 20-nm and 120-nm ZnO particles are a little different. For example, the blood viscosity could be induced by low and median dose of 20-nm ZnO but high dose of fine ZnO after oral administration. The edema and degeneration of hepatocytes, and inflammation of pancreas could be observed in most of the 20-nm ZnO treated mice. The 120-nm ZnO treated mice were found having dose-effect pathological damage in gastric, liver, heart and spleen, however, the 20-nm ZnO treated mice presented lessened liver, spleen and pancreas damage with the increase of treated dose.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the authors nano-scale as well as submicro-scale ZnO are both not classified according to the GHS with a LD50 of greater than 5 g/kg and 2g/mg < LD50 < 5 g/kg, respectively.
Executive summary:

In this work, the acute oral toxicity of 20- and 120-nm ZnO powder at doses of 1-, 2-, 3-, 4-, 5-g/kg body weight was evaluated referred to the OECD guidelines for testing of chemicals. As the results, both 20- and 120-nm ZnO belong to non-toxic chemicals according to the Globally Harmonized Classification System (GHS) for the classification of chemicals.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Zinc didocosanoate

No acute toxicity studies with zinc didocosanoate are available, thus the acute toxicity will be addressed with existing data on the individual moieties zinc and docosanoate.

Signs of acute oral toxicity are not expected for zinc ditetradecanoate, since for the moieties zinc and tetradecanoate have not shown signs of acute oral toxicity (LD50 > 2000mg/kg). Under the assumption that the moieties of zinc didocosanoate show their toxicological profile individually upon dissolution, the acute oral (systemic) toxicity of zinc didocosanoate can be calculated using the equation given in regulation (EC) 1272/2008, Annex I, Section 3.1.3.6.1.

Further, in a supporting study with the analogous substance zinc dilaurate, no toxicity was seen in an acute inhalation toxicity test up to the limit concentration of 5mg/L. Thus, acute toxic effects are not likely to occur. For further information on the toxicity of the individual moieties, please refer to the relevant sections in the IUCLID and CSR.

 

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

 

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.

Tetradecanoate

Acute oral toxicity

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).

Additionally, based on animal data reported in the HERA document on fatty acid salts (2002), fatty acids with chain lengths of C18 to C22 showed no toxicity after oral administration to rats. The LD50was set above 5000 mg/kg bw. (HERA, 2002).

“In an OECD TG 401 study, a group of five rats/sex was administered docosanoic acid (C22) at a dose of 2000 mg/kg bw. There were no clinical signs, deaths, or findings at necropsy. The LD50was > 2000 mg/kg bw.”(OECD SIDS, 2014).

Further on, no acute oral toxicity could be observed in animal experiments with fatty acids with similar chain lengths, such as stearic acid (C18) or oleic acid (C18:1).

“International-BioResearch (1974, as referred to by CIR, 1987) determined the acute oral toxicity in groups of five male albino rats. Animals were administered by gavage lauric-, myristic-, palmitic- or stearic acid with increasing doses of up to 10,000 mg/kg bw and oleic acid up to 20,000 mg/kg bw. It was observed that for all these fatty acids the LD50value was above the maximum level tested. No mortality was observed in five albino rats gavaged with 5 g/kg bw oleic acid (commercially supplied); clinical signs were not reported during the 7-day post-exposure period (CTFA, 1978, as referred to in CIR, 1987)” (EFSA ANS Panel, 2017).

“In an OECD TG 401 study, a group of five rats/sex was administered octadecanoic acid (as a 50% suspension in DMSO) at a dose of 5000 mg/kg bw. There was one death. Animals exhibited transient piloerection, excessive salivation, and diminished activity. At necropsy, the male animal that died exhibited a stomach full of test substance; surviving animals showed remnants of test substance in the stomach with swelling of the mucous membrane. The LD50 was > 5000 mg/kg bw” (OECD SIDS, 2014).

Justification for classification or non-classification

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

Zinc didocosanoate is not classified for acute inhalative toxicity because of lacking data.