Zinc bis(hydroxymethanesulphinate)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

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.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Effect of Dietary Zinc on the Absorption of Orally Administered Zn65

Author:

Furchner JE & Richmond CR

Year:

1962

Bibliographic source:

Health Phys. 8:35-40

Materials and methods

Objective of study:

absorption

Principles of method if other than guideline:

Effect of dietary zinc administration as Zinc acetate was evaluated on the absorption of orally administered Zn65 in rats.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Zinc chloride

EC Number:

231-592-0

EC Name:

Zinc chloride

Cas Number:

7646-85-7

Molecular formula:

Cl2Zn

IUPAC Name:

zinc dichloride

Details on test material:

- Name of test material (as cited in study report): Zinc chloride
- Specific activity (if radiolabelling): 1.2 µC

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 70 d
- Weight at study initiation: 280 g
- Fasting period before study: No
- Diet (e.g. ad libitum): Pulverized purina laboratory chow, ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 2 wk (with normal diet)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on exposure:

- Powdered Zinc acetate was added to the food (Pulverized purina laboratory chow) to make the concentration of Zinc 58, 117, 175, 293, 410 and 644 ppm and administered to the rats for 28 d.
- After 28 d of the zinc-supplemented dietary regimen, 1.2 µC of Zn62Cl was administered by gastric gavage while the animals were under light ether anaesthesia.

Duration and frequency of treatment / exposure:

Zinc chloride: Single exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
Zinc chloride: 1.2 µC
Zinc acetate: 58, 117, 175, 293, 410 and 644 ppm Zinc

No. of animals per sex per dose / concentration:

Nine

Control animals:

no

Positive control reference chemical:

No

Details on study design:

- Rationale for animal assignment: Random

Details on dosing and sampling:

- Whole-body activity was determined at 30 min and at 1, 2, 4, 7 and 11 d after injection in the Los Alamos Small Animal Counter (LASAC-III)
- Body weight: Recorded periodically

Statistics:

ANOVA followed by Duncan's test

Results and discussion

Preliminary studies:

Not applicable

Main ADME results

Type:

absorption

Results:

Retention (%) of Zinc from Zn65 in normal dietary zinc (~58 ppm): At Day 1: 20.22 ± 3.30; At Day 2: 14.86 ± 2.44; At Day 4: 12.73 ± 2.17; At Day 7: 10.74 ± 1.90; At Day 11: 9.22 ± 1.70

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Retention (%) of Zinc from Zn65 in normal dietary zinc (~58 ppm):
- At Day 1: 20.22 ± 3.30
- At Day 2: 14.86 ± 2.44
- At Day 4: 12.73 ± 2.17
- At Day 7: 10.74 ± 1.90
- At Day 11: 9.22 ± 1.70

Details on distribution in tissues:

Not applicable

Details on excretion:

Not applicable

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

Not applicable

Any other information on results incl. tables

Table 1. Effect of dietary zinc on the retention of orally administered Zn⁶⁵ in rats

Group No.	Stable Zinc in diet (ppm)	Day
		1	2	4	7	11
1	58	20.22 ± 3.30	14.86 ± 2.44	12.73 ± 2.17	10.74 ± 1.90	9.22 ± 1.70
2	117	15.86 ± 3.50	10.78 ± 2.28	9.04 ± 1.90	7.63 ± 1.57	6.47 ± 1.28
3	175	16.68 ± 6.00	9.52 ± 1.21	7.80 ± 1.09	6.57 ± 0.88	5.56 ± 0.78
4	293	14.26 ± 7.76	9.36 ± 6.69	7.77 ± 5.67	6.44 ± 4.71	5.42 ± 3.85
5	410	12.53 ± 3.97	5.96 ± 1.64	4.73 ± 1.17	3.95 ± 0.92	3.30 ± 0.79
6	644	13.15 ± 10.98	4.69 ± 2.55	3.45 ± 1.59	2.88 ± 1.23	2.32 ± 0.97

Study on human subject: Result

- At 10 d post-ingestion, excretion increased by more than a factor of 3
- Radioassay of fecal samples showed that, after the first ingestion, 11% of the Zn⁶⁵ was excreted during the first 4 d post ingestion and that, after the second ingestion, 44% was excreted during the first 3 d post ingestion.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other:
Retention of Zinc from Zn62Cl in rats fed with normal dietary zinc (~58 ppm) was determined to be 20.22 ± 3.30, 14.86 ± 2.44, 12.73 ± 2.17, 10.74 ± 1.90 and 9.22 ± 1.70 at 1, 2, 4, 7 and 11 d, respectively. Under the test conditions, dietary zinc was determined to be a major factor regulating the retention of Zinc in rats and human subject.

Executive summary:

A study was conducted to evaluate the effect of dietary zinc on the absorption of orally administered Zn⁶⁵ in rats.

 

Diet containing Zinc acetate (58, 117, 175, 293, 410 and 644 ppm Zinc) was administered to the rats for 28 d. After 28 d of the initiation of Zinc acetate diet, 1.2 µC of Zn⁶⁵Cl was administered by gastric gavage and whole-body activity was determined at 30 min and at 1, 2, 4, 7 and 11 d.

 

Retention of Zinc from Zn⁶⁵Cl in rats fed with normal dietary zinc (~58 ppm) was determined to be 20.22±3.30, 14.86±2.44, 12.73±2.17, 10.74±1.90 and 9.22±1.70 at 1, 2, 4, 7 and 11 d, respectively. Rats maintained on diets supplemented with Zinc acetate retained less Zn⁶⁵ than rats on normal diets. Addition of 6-10 times the normal Zinc intake reduced retention by a factor of 3. Data from human subject showed increase in excretion of Zn⁶⁵ after ingestion of Zinc acetate diet for 30 d.

Under the test conditions, dietary zinc was determined to be a major factor regulating the retention of Zinc in rats and human subject.