Zinc glycinate sulfate

Endpoint summary

Description of key information

The acute oral toxicity of zinc monoglycinate sulfate hydrate was determined in a read-across approach. The acute oral LD50 of zinc monoglycinate sulfate in rats is expected to be >2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

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

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

Specific details on test material used for the study:

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

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

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

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.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 710 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 260 - <= 2 330

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.

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	++	++	+

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.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019-08-07 to 2019-09-24

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

Federal Law No. 61–FZ “On the Circulation of Medicinal Products” of 12 April 2010 (as amended);Federal Law No. 323–FZ “On the Basics of Health Protection of the Citizens in the Russian Federation” of 21 November 2011 (as amended)

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: NPO House of Pharmacy (inhouse bred)
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Fasting period before study: 16h
- Housing: individually in standard transparent plastic cages. Wood pellets were used as bedding.
- Diet (e.g. ad libitum): Feed for laboratory animals PK-120-1 prepared in accordance with GOST R50258-92 "Compound Feeds for Laboratory Animals. Specifications” was given ad libitum
- Water (e.g. ad libitum): purified water normalized in respect of organoleptic properties, pH, solids, reducing substances, carbon dioxide, nitrates and nitrites, ammonia, chlorides, sulphates, calcium and heavy metals in accordance with SanPiN 2.1.4.1074-01 "Drinking Water. Hygienic Requirements for the Quality of Water from Centralized Drinking Water Supply Systems. Quality Control". Water in standard drinking bowls with steel nose caps was given ad libitum.
- Acclimation period: 5 days
- Method of randomisation in assigning animals to test and control groups: Randomization was not expected in this study, since dosing occurred in stages and individually. The main criterion for including an animal in the experiment was its body weight.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26 °C
- Humidity (%): 30-70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From:
No. 2.0-31.05/19 of 31 May 2019
No. 2.0-30.06/19 of 01 July 2019

Route of administration:

oral: gavage

Vehicle:

other: 1% starch solution

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Before administration, suspensions of the test article was prepared with concentrations of ≈ 29.2 mg/ml for 175 mg/kg, ≈ 91.7 mg/ml for 550 mg/kg and 333.3 mg/ml for 2000 mg/kg.
- Amount of vehicle (if gavage): 1.5 mL per 250g rat
- Lot/batch no. (if required): М-3.38/19
MAXIMUM DOSE VOLUME APPLIED: 333.3 mg/mL

CLASS METHOD
- Rationale for the selection of the starting dose:since the test article is presumably a low toxicity substance, 175 mg/kg was selected as the starting dose for a single intragastric administration to one male and one female rat.

Doses:

175, 550, 2000 mg/kg bw

No. of animals per sex per dose:

175 mg/kg bw: 1 animal; 550 mg/kg bw: 4 animal; 2000 mg/kg bw 6 animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: On day 1, 2, 7 and 15
- Necropsy of survivors performed: yes
- Clinical signs: daily
- Other examinations performed: other:Clinical examination on day 2, 7, 14 and local tolerance evaluation on day 15

Statistics:

Calculation of LD50 with confidence intervals was performed using the AOT 425 StatPgm program (Westat, USA).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 300 - <= 2 000 mg/kg bw

Based on:

act. ingr.

95% CL:

> 864.4 - < 4 210

Mortality:

Following administration of the test article at 2000 mg/kg, 4 male and 4 female rats died. Death was recorded 48 hours after the administration in 58% of animals (4 males and 3 females). Only in one female, death was recorded 2 hours after administration. The immediate cause of death of all animals was acute heart failure.

Clinical signs:

other: Clinical signs of intoxication were recorded in animals treated with a single intragastric dose of Plexomin® Zn 2000 mg/kg, and which were manifested as dyspnoea and wheezing, depressed behaviour with decreased response to external stimuli, ruffled fur an

Gross pathology:

No gross abnormalities in the internal organs were identified at the scheduled necropsy in experimental animals treated with a single intragastric dose, however, during unscheduled necropsy, foci of oedema, emphysema and haemorrhagic impregnation of lung tissue, venous congestion of internal organs, as well as mild and moderate congestion of the brain vessels were found in all animal bodies. The immediate cause of death of the animals was acute heart failure.

Other findings:

The test article Plexomin® Zn following a single-dose intragastric administration had a moderate local irritant effect, which was manifested as catarrhal gastritis in animals when administered at doses of 175 mg/kg (in 1 female) and 550 mg/kg (in 1 male) and as a film of the test article on the gastric mucosa at 2000 mg/kg. The abnormalities identified in the animals that received the test drug at 2000 mg/kg were reversible.

A total of 4 male and 4 female rats died. Animals Nos. 3, 7, 9, 11, 18, 22, 24 and 26 treated with the test article, Plexomin^®Zn 2000 mg/kg, died.

The bodies of all animals that died during the study were subjected to a necropsy and gross examination.

Table 1: Incidence of abnormalities according to the necropsy results of rats treated with the test article (number of animals with identified abnormality/total number of animals)

Organs	Abnormalities identified	Plexomin^®Zn feed additive (Phytobiotics Futterzusatzstoffe GmbH, Germany)
		2000 mg/kg
		males	females
Lungs	Foci of emphysema, oedema and haemorrhagic impregnation of the tissue	4/4	4/4
Internal organs	Venous congestion	4/4	4/4
Brain	Oedema and vascular congestion	4/4	4/4

The necropsy of animals subjected to a scheduled euthanasia did not find any abnormalities in the internal organs following single intragastric doses of the test article, Plexomin^®Zn of 175 mg/kg, 550 mg/kg and 2000 mg/kg.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 value for the test item is >300 and <= 2000 mg/kg following single-dose intragastric administration to male and female rats. The test item can be classified as toxicity category 4 according to the international GHS classification.

Executive summary:

In an acute oral toxicity study according to OECD Guideline 425, groups of male and female Sprague-Dawley rats, 8-12 weeks old were given a single oral dose of bis(glycinato-N,O)zinc (% a.i.) in 1% starch solution at doses of  175, 550, or 2000 mg/kg bw and observed for 15 days.

Oral LD50 Combined [males/females]= >300 and <2000 mg/kg bw (95% C.I. 864.4–4210 mg/kg).

Bis(glycinato-N,O)zincis of low toxicity based on the LD50 in both female and male rats.

The first symptoms were observed 5 minutes after administration in 67% of male and female rats that received the test item at 2000 mg/kg. The toxic effect was manifested as dyspnoea and wheezing, depressed behaviour. Ruffled fur and decreased response to picking up and sound stimuli (a clap) were noted in these animals 30 minutes after administration. Forced lying on the stomachs was also noted in one male and female. The female rat developed diarrhoea 30 minutes after administration. Another female rat treated with the test substance at 2000 mg/kg developed ataxia 3 hours after administration, which was manifested as incoordination and bouncing when moving. Symptoms of intoxication persisted in animals until death, which was recorded in 58% of animals 48 hours after administration. Only in one female, death was recorded 2 hours after administration. The immediate cause of death of all animals was acute heart failure. The animals that received the test substance at doses of 175 mg/kg and 550 mg/kg exhibited no symptoms of intoxication.

In two males and females which received the test item at 2000 mg/kg, signs of intoxication were observed 1 to 2 hours after administration, which were manifested as depressed behaviour and ruffled fur. Also, decreased muscle tone was recorded in another female 2 hours after administration. Symptoms of intoxication were reversible and animal condition improved 24 hours after administration. No changes in body weight gain or body weights were observed in all animals. The data obtained allow concluding that the NOAEL for bis(glycinato-N,O)zinc is < 175 mg/kg following single-dose intragastric administration to rats.

Based on these results, bis(glycinato-N,O)zinc is classified according to the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) as Category 4 'Harmful if swallowed' with respect to acute oral toxicity.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD Guideline 407

Version / remarks:

adopted 03 October, 2008; study was principally conducted according to Partial Revision of Guidelines for Repeated-dose Toxicity
Studies. Notification No. 655 of the Pharmaceutical and Medical Safety Bureau. Ministry of Health and Welfare, Japan. 1999.

GLP compliance:

no

Remarks:

compliance to GLP guidelines was not reported

Test type:

other: 28-days repaeted dose oral toxicity study

Limit test:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan Inc. (Kanagawa, Japan)
- Age at study initiation: Five-week-old
- Weight at study initiation: 193.9 to 215.1g
- Housing: individually in metallic bracket cages
- Diet (e.g. ad libitum): allowed ad libitum access to a gamma-ray sterilized powder diet (CRF-1; Oriental Yeast Co., Ltd., Tokyo, Japan).
- Water (e.g. ad libitum): allowed ad libitum access to tap water
- Acclimation period: 6 days prior to experimentation

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 26°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 15 to 15 cycles per hour
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Water for injection (D.W., lot 5A88; Otsuka Pharmaceutical Factory Inc., Tokushima, Japan)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50, 100 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Lot/batch no. (if required): lot 5A88

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Absence of toxic effects in other studies with the test substance

Doses:

500, 1000 and 2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

yes

Details on study design:

- Duration of observation period following administration: based on study design the duration of exposure was 28-days/once daily, after that period the animals were sacrificed and a gross observation as well as histopathological determination was performed.
- Frequency of observations and weighing: All animals were examined twice daily (pre-dose and post-dose) for clinical signs. Individual body weights were recorded for all animals on days 1, 3, 8, 15, 22 and 28 and on the day of necropsy. Food consumption and water consumption on days 2–3, 7–8, 14–15, 21–22 and 27–28 was measured individually for all animals.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, hematology, urinalysis, blood chemistry

Statistics:

Body weight, food consumption, water consumption, urinalysis, hematology, blood chemistry, and organ weight data were recorded using a MiTOX RDT system. Numerical data obtained during the study were used to calculate group mean values and standard deviations. Group variances for the appropriate parameters were compared using Bartlett’s method. When the differences between group variances were not significant, Dunnett’s multiple comparison method was applied to determine the significance of differences be tween the control group and each glycine-treated group. If the Bartlett’s test indicated significant differences between group variances for a given parameter, that parameter was compared among groups using the Steel’s multiple comparison method for mean ranking. The criterion of significance was an alpha level of 0.05 or 0.01.

Key result

Sex:

male

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: under the present conditions there were no toxic effects detectable up to the concentrations used in this test

Mortality:

Not observed

Clinical signs:

other: not adverse effects observed

Gross pathology:

No abnormalties detected

Other findings:

- Other observations: Daily urine volume and total amount of Cl excretion were significantly higher (p<0.05) in the 2000 mg/kg dose group. Statistically significant increases in daily urinary volume and total amount of urinary Cl, and declining trends in urine pH and urinary protein in the glycine 2000 mg/kg dose group were considered to be of little toxicological significance, because there were no histopathological correlates in the kidneys and urinary bladder and no changes in kidney weight or other urinary parameters.

Interpretation of results:

GHS criteria not met

Conclusions:

In the present study conducted similarly to OECD guideline 407 and performed according to Partial Revision of Guidelines for Repeated-dose Toxicity Studies. Notification No. 655 of the Pharmaceutical and Medical Safety Bureau. Ministry of Health and Welfare, Japan. 1999, Glycine showed no adverse effects when administered to male rats for 28 days once daily. However, there were significant changes in urine volume and urinary Cl concentrations but since these effects had no hisotpathologic correlate these effects are regarded not toxicological relevant. Based on the results presented here glycine does not need to be classified according to Regulation (EC) No. 1272/2008 (CLP) and the Harmonized System for Classification and Labelling of Chemcials (GHS).

Executive summary:

In a Repeated Dose, 28-day Oral Toxicity Study performed similar to OECD guideline 407 Glycine was administered to groups of 6 male and 6 female Crj: CD(SD) rats by oral gavage at dose levels of 500, 1000 and 2000 mg/kg bw/day for 28 days. The control group animals received Water for injection (D.W., lot 5A88; Otsuka Pharmaceutical Factory Inc., Tokushima, Japan).

All animals survived to study termination. No test substance-related findings were detected or observed in clinical examinations, body weights, food consumption values, clinical biochemistry and clinical pathology evaluations. During the anatomical pathology examinations, no test substance-related findings were observed or detected during macroscopic examinations, organ weight evaluations or microscopic examinations. Daily urine volume and total amount of Cl excretion were significantly higher (p<0.05) in the 2000 mg/kg dose group. Statistically significant increases in daily urinary volume and total amount of urinary Cl, and declining trends in urine pH and urinary protein in the glycine 2000 mg/kg dose group were considered to be of little toxicological significance, because there were no histopathological correlates in the kidneys and urinary bladder and no changes in kidney weight or other urinary parameters.

There is no evidence for specific target organ toxicity in this study.

The LD0 is 2000 mg/kg bw/day in this study.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

no guideline followed

Principles of method if other than guideline:

The acute oral toxicity of glycine in rats was investigated.

GLP compliance:

no

Remarks:

Study was conducted prior to implementation of GLP Guidelines

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Age at study initiation: at 7 weeks of age
Weight at study initiation: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23±2 °C
- Humidity (%): 55 ± 5 °C
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:

oral: gavage

Vehicle:

physiological saline

Details on oral exposure:

Manufacture, supplier, source of supply: Iwai Chemicals Co.
Lot/batch No.: no data

Doses:

more than 4 doses (unspecified)

No. of animals per sex per dose:

5-10 animals per dose

Control animals:

not specified

Details on study design:

Duration of observation period following administration: 7 days
Frequency of observations and weighing:no data
Necropsy of survivors performed: yes
Other examinations performed: clinical signs

Statistics:

According to Litchfield and Wilcoxon

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

7 930 mg/kg bw

Based on:

test mat.

95% CL:

> 7 329 - < 8 580

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

9 550 mg/kg bw

Based on:

test mat.

95% CL:

> 8 917 - < 10 228

Mortality:

Not reported

Clinical signs:

other: Decrease in in locomotor activity, slightly respiratory depression, piloerection and ptosis were observed in female and male rats at 15 to 35 min after dosing. Most of the animals stopped breathing after muscle weakness, cyanosis, circular movement, tonic

Gross pathology:

Congestion in lungs and dot hemorrhage in glandular stomach were observed in some animals. No abnormal gross findings in the other organs were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The information gathered during research of literature revealed the present results from the TOXNET database. In the study of Yakuri et al., 1977 mice and rats were treated with several doses of glycine either intraperitoneal, subcutaneous or orally. The LD50 value was calculated according to the method of Litchfield and Wilcoxon. The LD50 value for female rats was determined to be 7930 mg/kg bw and for male rats 9550 mg/kg bw.
Based on these results glycine does not need to be classified according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).

Executive summary:

In an acute oral toxicity study , Wistar strain rats were administered single oral doses of glycine at at least four increasing doses in physiological saline, 5 animals per group, and were observed for 7 days.

The LD50 value was calculated according to Litchfield and Wilcoxon.

The number of animals that had died was not reported, only the calculated LD50 Values were provided. Clinical signs reported were decrease in in locomotor activity, slightly respiratory depression, piloerection and ptosis were observed in female and male rats at 15 to 35 min after dosing. Most of the animals stopped breathing after muscle weakness, cyanosis, circular movement, tonic convulsion. Some animals stopped breathing after coma without tonic convulsion. But some rats became a coma and caused breathing to stop without tonic convulsion. Necropsy findings were: Congestion in lungs and dot hemorrhage in glandular stomach were observed in some animals. No abnormal gross findings in the other organs were observed.

Oral LD50 (rat, females) 7930 mg/kg bw

Oral LD50 (rat, males) 9550 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

The studies were conducted according to or similar to OECD guidelines and have been assigned a reliability of 1 or 2. Overall, the study design of the source studies is adequate and reliable for the purpose of this read-across approach. The structural similarity of the target and source substance justifies a high level of confidence in the ability to predict similar toxicological properties. The results of the study are adequate for classification and labelling and for risk assessment purposes.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The acute oral toxicity of zinc monoglycinate sulfate hydrate was determined in a read-across approach. As source and target substances only differ in the number of glycine molecules in their chemical structure, this read-across approach has been carried out under the assumption that the difference in composition does not contribute to the acute oral toxicity of the substance because glycine has been proven to be non-toxic via the oral route in rats (Shibui et al. 2013, Yakuri 1977).

In a guideline study according to OECD 425, the acute oral LD50 of the source substance zinc bisglycinate was 2000 mg/kg bw which is equivalent to 2200 mg zinc monoglycinate sulfate/kg bw or, in form of a hydrate, 2384 mg/kg bw.

In the publication by Domingo et al., 1988, the acute oral LD50 of the source substance zinc sulfate was determined to be 1710 mg/kg bw, equivalent to 623 mg of Zn²⁺/kg bw. Based on these results, the acute oral LD50 of zinc monoglycinate sulfate is 2238 mg/kg bw or, in form of a hydrate, 2425 mg/kg bw.

These results substantiate the assumption that the difference in the number of glycine molecules in the chemical structure does not influence on the acute oral toxicity of both source and target substances, but that Zn²⁺ is the toxicologically relevant component.

According to these results, the acute oral LD50 of zinc monoglycinate sulfate in rats is expected to be >2000 mg/kg bw.