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Description of key information

Assessment of the acute oral toxicity of zinc bis(dihydrogen phosphate) was studied in Wistar CRL/WI rats according to OECD guideline no 423 (Acute toxic Class Method) .The LD50 value was established to be within the range of >300 to <2000 mg/kg bw. According to OECD 423 test guideline and based on the LD50 cut-off values, the LD50 value was considered to be 1000mg/kg bw. 
There are no specific data for zinc bis(dihydrogen phosphate) available on which to evaluate for acute inhalation and dermal toxicity. Read-across towards soluble zinc chloride and zinc sulphate, indicates that zinc bis(dihydrogen phosphate) is of very low acute inhalation and dermal 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:
not applicable
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented and scientifically good . According to GLP and to specific OECD Guideline.
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland , Sulzfeld, Germany
- Weight at study initiation: body weight variation did not exceed ± 20% of the sex mean
- Fasting period before study: food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance
- Housing: 3 animals per cage in labeled Macrolon cages (MIV type; height 18cm) containing sterilised sawdust as bedding material and paper as cage-enrichment
- Diet: plleted rodent diet (SM R/M-Z from SSNIFF Spezialdiäten GmbH, Soest, Germany) ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
oral gavage, using plastic feeding tubes
Doses:
300 mg/kg and 2000mg/kg active ingredient
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: up to death
- Frequency of observations and weighing:
mortality/viability: twice daily
body weights: days1 (pre-administration), days 8 and 15 and at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
no statistics reported
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 300 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: All six animals survived
Sex:
female
Dose descriptor:
LD50
Effect level:
< 2 000 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: 2of 3 females died
Mortality:
300mg/kg active ingredient - deaths: 0/3 (females)
300mg/kg active ingredient -deaths: 0/3 (males)
2000mg/kg active ingredient - deaths: 2/3 (females)
the decedents were found within 24 hours post-treatment
Clinical signs:
other: 300mg/kg active ingredient - lethargy, hunched posture, rales, shallow respiration, piloerection, salivation, chromodaccryorrhoea,ptosis 2000mg/kg active ingredient - lethargy, hunched posture, uncoordinated movements, piloerection, ptosis the surviving a
Gross pathology:
macroscopic post mortem examination of the animals found died during the study revealed abnormalities in the stomach (irregular surface and many black/brown foci in the glandular mucosa) and reddish discolouration of the mesenteric lymph nodes. No abnormalities were revealed in the surviving animals
Other findings:
none

none       

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of SAT 060267 (active ingredient) in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.
According to OECD 423 test guideline and based on the LD50 cut-off values, the LD50 value was considered to be 1000mg/kg bw.
Based on these results:
- according to the GHS classification, SAT 060267 should be classified as : harmfull if swallowed (category 4) for acute toxicity by the oral route
- according to EC criteria for classification and labelling for dangerous substances and preparations, SAT 060267 should be labelled as: harmfull if swallowed (R22)
Executive summary:

This study report demonstrated that the sample SAT 060267 is harmful if swallowed for actue toxicity by the oral route. The oral LD50 value of SAT 060267 (active ingredient) in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.

According to OECD 423 test guideline and based on the LD50 cut-off values, the LD50 value was considered to be 1000mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 000 mg/kg bw

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
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:
other: 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 selection of acute toxicity – oral endpoint
Only one study available on zinc bis(dihydrogen phosphate) and has Klimisch score 1

Justification for classification or non-classification

Soluble zinc bis(dihydrogen phosphate) is harmful following acute oral exposure (LD50 range >300 to <2000 mg/kg bw. According to OECD 423 test guideline and based on the LD50 cut-off values, the LD50 value was considered to be 1000mg/kg bw and meets the classification criteria for harmful if swallowed: Acute Tox. Cat. 4: H302. Zinc bis(dihydrogen phosphate) is based on read-across data of very low acute inhalation and dermal toxicity not requiring a classification according to EC criteria.

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