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Description of key information

Assessment of the acute oral toxicity of zinc chloride was studied in Sprague-Dawley rats and Swiss mouse according to OECD guideline no 401 .The LD50 value was within the range of 1,100 to 1,260 mg/kg bw. 
In the 10 min inhalation study in female Sprague-Dawley rats, zinc chloride has demonstrated acute toxicity via the inhalation route (LC50 ≤ 1,975 mg/m3). However, since the exposure of the animals to the size of the particles is not truly representative of exposure to humans under normal conditions, it is difficult to assess whether or not, zinc chloride is acutely toxic since a four hour LC50 value could not be derived and a clear dose-response relationhip coud not be established.
Airway irritation has been observed both in animals and in humans, zinc chloride has the potential to be a respiratory tract irritant.

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:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(No data about doses, controls, observation frequency, fasting period before study, age at study initiation, housing of animals)
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Panlab (Barcelona, Spain)
- Age at study initiation: No data
- Weight at study initiation: 230-280 g
- Fasting period before study: No data
- Housing: No data
- Diet: Standard pellet diet (Panlab, Barcelona, Spain), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 7 d
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 1 mL/300 g body weight


DOSAGE PREPARATION: Solutions were administered at pH between 6.0 and 7.0. Sodium bicarbonate was used to adjust the pH when necessary.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A preliminary screening with small groups of 3 animals of each kind was carried out The LD50 values were then calculated according to the Litchfield and Wilcoxon method.
Doses:
No data
No. of animals per sex per dose:
Preliminary screening: Three
Main study: Ten
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: No
- Other examinations performed: Clinical signs and weight gain

Statistics:
No data
Preliminary study:
A preliminary screening with small groups of three animals of each kind was carried out. The LD50 values were then calculated according to the Litchfield and Wilcoxon method
Sex:
male
Dose descriptor:
LD50
Effect level:
1 100 mg/kg bw
95% CL:
661 - 1 830
Remarks on result:
other: Equivalent to 528 mg of Zn/kg
Mortality:
Mortality observed mostly during the first 48 h of test material administration. No deaths occurred after three days.

Clinical signs:
Miosis, conjunctivitis and hemorrhages and hematomas in the tail.
For details see Table 1 in "Remark on results including tables and figures" field

Body weight:
Slight weight loss
Gross pathology:
No data
Other findings:
No data

Table 1. Severity of physical and clinical signs in rats after zinc intoxication in a single dose

 

Number of days after zinc administration

1

2-3

4-7

8-14

Mortality rates on oral administration

90%

10%

0%

0%

Miosis

+

++

++

+

Conjunctivitis

+

++

+

None

Erythema, necrosis in nose

None

++

++

++

Exophthalmos

None

None

None

None

Degreased food and water consumption, weight loss

None

+

+

None

Hemorrhages and hematomas in the tail

None

++

++

+

Mortality rates and physical and observational examination of rats are average for all zinc compounds.

+Light; ++Moderate

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the acute oral LD50 of the test material in Sprague-Dawley rats was calculated to be 1,100 mg/kg (equivalent to 528 mg of Zn/kg).

Executive summary:

A study was conducted to evaluate the acute oral toxicity of the test material in Sprague-Dawley rats according to the OECD Guideline 401 (Acute Oral Toxicity).

Initially a preliminary screening with small groups of three rats of each kind was carried out and the LD50 values were then calculated according to the Litchfield and Wilcoxon method. The main study was conducted with ten rats.

Miosis, conjunctivitis, decreased consumption of food and water and hemorrhages and hematomas in the tail were observed in the rats.

Under the test conditions, the acute oral LD50 of the test material in Sprague-Dawley rats was calculated to be 1,100 mg/kg (equivalent to 528 mg of Zn/kg).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 100 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:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Principles of method if other than guideline:
Sprague-Dawley rats were exposed for 10 min to the test material followed by observations of clinical signs and mortality. After 7 d observation time animals were anesthetized and lungs were examined.
GLP compliance:
no
Test type:
other: Acute Inhalation Toxicity
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: ALAB, Sollentuna, Sweden
- Age at study initiation: 60-80 d
- Weight at study initiation: 200-250 g

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23 °C
- Humidity (%): 50-60 %



Route of administration:
inhalation: aerosol
Type of inhalation exposure:
head only
Vehicle:
other: water
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Inhalation chamber operated in dynamic mode
- Exposure chamber volume: 8.4L
- Method of holding animals in test chamber: Perspex cylinders
- System of generating particulates/aerosols: Generated from a solution of test material in water (3.7 and 10.3 M with specific gravity 1.3 and 7.1 g/mL) by means of Collision nebulizer
- Method of particle size determination: Cascade impactors of the Battelle type (Mitchell and Pilcher 1959) using a sampling flow of 1L/min

TEST ATMOSPHERE
- Brief description of analytical method used: Particles collected on membrane filters (Millipore, AAWP, pore size 0.45 µm), filters extracted in 4 M HNO3, extract analyzed by flame atomic absorption spectrometer (air-acetylene flame, 213.9 nm)
- Samples taken from breathing zone: Yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Non-uniform
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.3 and 2.6 µm


Analytical verification of test atmosphere concentrations:
yes
Remarks:
flame atomic absorption spectrometer (air-acetylene flame, 213.9 nm)
Duration of exposure:
10 min
Concentrations:
600, 940, 1220 and 1950 mg Zn/m3 (molar ratio of Zn: ZnCl2 is 1:2.1)
No. of animals per sex per dose:
Three
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 7 d
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, mortality, gross pathology and histopathology
Statistics:
Not reported
Preliminary study:
Not applicable
Sex:
female
Dose descriptor:
LC50
Effect level:
<= 1 975 mg/m³ air (analytical)
Exp. duration:
10 min
Mortality:
Two animals died at 940 and 1,220 mg/m3 while all animals died at highest dose of 1,950 mg/m3. For details see ‘table 1’
Clinical signs:
other: Respiratory distress including dyspnoea, decreased locomotor activity, laboured breathing, rhonci and rales observed.
Body weight:
Not reported
Gross pathology:
Entire surface of lungs showed discolouration (dark red), varying degrees of congestion, patchy discolouration, oedema and interstitial emphysema
Other findings:
- Histopathology: Atelectasis, hyperaemia and haemorrhages and oedema observed
- Potential target organs: Lungs

Table 1: Acute inhalation toxicity of test material in rats

 Concentration (mg Zn/m3)*  Mortality after exposure during 10 min (number of deaths/exposed)
 600  0/3
 940  2/3
 1,220  2/3
 1,950  3/3

* The molar ratio of Zn: ZnCl2 is 1:2.1

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on these results, the acute inhalation LD50 of the test material was calculated to be approximately 2,000 mg ZnCl2/m3 in rats.
Executive summary:

A study was conducted in Sprague-Dawley female rats to determine pulmonary injury after acute inhalation exposure to the test material.

Animals were exposed to the test material at a concentration of 600, 940, 1,220 and 1,950 mg Zn/m3 (molar ratio of Zn: ZnCl2 is 1:2.1) for 10 min. Animals showed respiratory distress. Clinical examination of lung showed discolouration (dark red), varying degrees of congestion, patchy discolouration, oedema and interstitial emphysema, atelectasis, hyperaemia and haemorrhages.

Based on the above results, the acute inhalation LD50 of the test material was calculated to be approximately 2,000 mg ZnCl2/m3 in rats.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
1 975 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Used in EU risk assessment report for zinc sulphate, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Type of coverage:
semiocclusive
Vehicle:
not specified
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
Details on study design:
observation period of 15 days
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
none
Clinical signs:
no effects
Body weight:
no effects
Gross pathology:
no effects
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 dermal is >2000 mg/kg bwZinc sulphate is not harmful or toxic via the dermal route
Executive summary:

In this study zinc sulphate heptahydrate was administered to the skin of five Wistar rats of each sex at 2000 mg/kg bw for 24 hours. Animals were observed for 15 days. Clinical signs of toxicity consisted of erythema (grade 1 and 2, of maximum grade 4), scales and/or scabs (scale 1 and 2, of maximum scale 3) in the treated skin area between observation days 2-8.

Zinc sulphate is not harmful or toxic via the dermal route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Soluble zinc chloride is harmful following acute oral exposure (LD50range 1,100 to 1,260 mg/kg bw). Zinc chloride has also demonstrated acute toxicity via the inhalation route (LC50≤ 1,975 mg/m3). However, since the exposure of the animals to the size of the particles is not truly representative of exposure to humans under normal conditions, it is difficult to assess whether or not, zinc chloride is acutely toxic since a four hour LC50value could not be derived and a clear dose-response relationhip coud not be established. Airway irritation has been observed both in animals and in humans, zinc chloride has the potential to be a respiratory tract irritant.

Soluble zinc sulphate (monohydrate, hexahydrate and heptahydrate) has LD50oral values ranging from 574 to 2,949 mg/kg bw, 862 to 4,429 mg/kg bw and 920 to 4,725 mg/kg bw, respectively for the three forms of zinc sulphate. Zinc sulphate is not acutely toxic via the dermal route (LD50 >2,000 mg/kg bw). Effects of inhalation exposure to zinc sulphate were limited to pulmonary effects only.

Soluble zinc bis(dihydrogen phosphate) is also harmful following acute oral exposure (LD50 range >300 to <2000 mg/kg bw).

While no specific acute toxicity data were identified for diammonium tetrachlorozincate and triammonium pentachlorozincate, it is (due to its similar solubility characteristics) likely to display a toxicity profile similar to that of zinc chloride, zinc sulphate or zinc bis(dihydrogen phosphate).

Justification for classification or non-classification

Soluble zinc chloride is harmful following acute oral exposure (LD50 range 1,100 to 1,260 mg/kg bw) and is classified as harmful if swallowed (Xn; R22 or Acute Tox. Cat. 4: H302) according to EC criteria.

Zinc chloride has also demonstrated acute toxicity via the inhalation route (LC50 ≤ 1,975 mg/m3). However, since the exposure of the animals to the size of the particles is not truly representative of exposure to humans under normal conditions, it is difficult to assess whether or not, zinc chloride is acutely toxic since a four hour LC50 value could not be derived and a clear dose-response relationhip coud not be established.

Zinc chloride is based on read-across data of very low acute dermal toxicity not requiring a classification according to EC criteria.