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Toxicological information

Acute Toxicity: other routes

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Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting 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
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Acute Zinc Intoxication: Comparison of the Antidotal Efficacy of Several Chelating Agents
Author:
Domingo J L, Llobet J M, Paternain J L and Corbella J
Year:
1988
Bibliographic source:
Vet Hum Toxicol 30(3): 224-228

Materials and methods

Test guideline
Qualifier:
no guideline followed
Deviations:
not applicable
Principles of method if other than guideline:
The test material was administered to mice intraperitoneally for 14 d to determine the acute intraperitoneal LD50.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Zinc sulphate (purchased from E Merck (Darmstadt, FRG)
- Other: Source - E Merck (Darmstadt, FRG)

Test animals

Species:
mouse
Strain:
Swiss
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: 24-28 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

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
not specified
Details on exposure:
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 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

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
316 mg/kg bw
95% CL:
205 - 488
Remarks on result:
other: Equivalent to 115 mg of Zn/kg
Mortality:
Mortality occurred mostly during the first 48 h of the test material administration. No deaths occurred after three days.
Clinical signs:
Conjunctivitis, piloerection, decreased food and water consumption and hemorrhages and hematomas in the tail were observed in the treated animals. These clinical signs appeared within the first 48 h and decreased/disappeared with time.
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

Any other information on results incl. tables

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

 

Number of days after zinc administration

1

2-3

4-7

8-14

Mortality rates on intraperitoneal administration

90%

10%

0%

0%

Conjunctivitis

None

+

+

None

Piloerection

None

+

+

+

Hemorrhages and hematomas in the tail

None

+

+++

+++

Degreased food and water consumption, weight loss

None

+

+

None

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

+Light; ++Moderate; +++Severe

Applicant's summary and conclusion

Conclusions:
Based on the above results, the acute intraperitoneal LD50 of the test material in Swiss albino mice was determined to be 316 mg/kg (equivalent to 115 mg of Zn/kg).
Executive summary:

A study was conducted to evaluate the acute intraperitoneal toxicity of the test material in Swiss albino mice.

Initially a preliminary screening with small groups of three mice was carried out and the LD50 values were then calculated according to the Litchfield and Wilcoxon method. In the main study, the test substance was administered in ten mice.

Mortality was observed mostly during the first 48 h after test material administration. Conjunctivitis, piloerection, hemorrhages, hematomas in tail and decreased food and water consumption were observed in the treated mice.

Based on these results, the acute intraperitoneal toxicity of LD50 was determined to be 316 mg/kg (equivalent to 115 mg of Zn/kg).