Zinc glycinate sulfate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Acute Zinc lntoxication: Comparison of the Antidotal Efficacy of Several Chelating Agents

Author:

Domingo JL, Llobet JM, Paternain JL

Year:

1988

Bibliographic source:

Vet Hum Toxicol 30(3): 224-228

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

before 2002

Deviations:

yes

Remarks:

Lack of information about doses, controls, observation frequency, fasting period before study, age at study initiation and housing

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Zinc sulphate

EC Number:

231-793-3

EC Name:

Zinc sulphate

Cas Number:

7733-02-0

Molecular formula:

H2O4S.Zn

IUPAC Name:

zinc sulfate

Details on test material:

ZnSO4 is soluble in water, toxicity based on free ion concentration

Specific details on test material used for the study:

- zinc was administered as zinc sulphate dihydrate (Merck, Germany)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Panlab, Spain
- Rationale for use of males: not provided
- Weight at study initiation: 230-280 g
- Diet: standard pellet diet ad libitum
- Water: tap water ad libitum
- Acclimation period: 7 days

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

physiological saline

Details on oral exposure:

VEHICLE
- Amount of vehicle: 1 mL per 300 g body weight
DOSAGE PREPARATION: solution concentrations were adjusted so that a 300 g rat received 1 mL and a 30 g mouse 0.2 mL. All solutions were given at a pH between 6.0 and 7.0. Sodium bicarbonate was used to adjust the pH when necessary.
- Rationale for the selection of the starting dose: A preliminary screening with 3 rats was carried out. The LD50 values were then calculated according to the Litchfield and Wilcoxon method.

Doses:

not reported

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: no
- Clinical signs including body weight: yes
- Mortality and clinical signs were checked 1, 2-3, 4-7 and 8-14 days after zinc administration.

Statistics:

not reported

Results and discussion

Preliminary study:

A preliminary screening with a small group of 3 rats was carried out. The LD50 values were then calculated according to the Litchfield and Wilcoxon method.

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 710 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 260 - <= 2 330

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

623 mg/kg bw

Based on:

test mat.

95% CL:

>= 460 - <= 846

Remarks on result:

other: LD50 values calculated for Zn2+

Mortality:

Mortality occurred during the first 24 h of the test material administration. No deaths occurred after three days.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

Between day 2 and day 7, a slight decrease in food and water consumption and weight loss was observed.

Any other information on results incl. tables

Table 1: Severity of physical and clinical signs in rats after zinc intoxication in a single dose. Mortality rates and physical and observational examination of rats are average for all zinc compounds examined in this study (zinc acetate, chloride, nitrate and sulphate).

Symptomatology: + light; ++ moderate

	Number of days after zinc administration (d)
	1	2-3	4-7	8-14
Mortality rate	90 %	10 %	0 %	0 %
Clinical signs
Miosis	+	++	++	+
Conjunctivitis	+	++	+	none
Erythema, necrosis in nose	none	++	++	++
Decreased food and water consumption, weight loss	none	+	+	none
Haemorrhages, haematoma and necrosis in tail	none	++	++	+

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 of zinc sulphate dihydrate in Sprague-Dawley rats was determined to be 1710 mg/kg, which is equivalent to 623 mg of Zn2+/kg.

Executive summary:

In the publication by Domingo et al., 1988, the acute oral toxicity of zinc sulphate dihydrate was examined in Sprague-Dawley rats similar to OECD guideline 401.

The test item was administered by gavage. In a preliminary study, three rats were used to determine the LD50 according to the Litchfield and Wilcoxon method. The main study was carried out with ten male rats. The publication lacks information about doses, controls, observation frequency, fasting period before study, age at study initiation and housing.

Mortality was observed, which occurred mainly in between 24 hours after dosing. No deaths occurred after three days. At the day after dosing, miosis and conjunctivitis occurred. From day 2-7 after dosing, miosis, conjunctivitis, erythema, decreased food and water consumption, weight loss and haemorrhages, haematoma and necrosis in the tail were reported. In between day 8-14 after dosing, miosis, erythema and haemorrhages, haematoma and necrosis in the tail were observed.

Based on these results, the acute oral LD50 of zinc sulphate dihydrate in male Sprague-Dawley rats was determined to be 1710 mg/kg bw, which is  equivalent to 623 mg of Zn²⁺/kg bw.