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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
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
Justification for data waiving:
other:
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1993

Materials and methods

Objective of study:
absorption
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Oral zinc tolerance test was performed in humans to study the absorption of zinc from various zinc compounds including zinc oxide.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Zinc oxide
Radiolabelling:
no

Test animals

Species:
human
Strain:
other: not applicable
Sex:
male/female
Details on test animals and environmental conditions:
Age: 51-66 yr
Race: Six were black and four were white
Exclusion criteria: Malignancy, diabetes, rheumatoid arthritis, alcoholism, chronic liver or renal disease, malabsorption syndrome, use of medications that may affect zinc metabolism, and any chronically debilitating illness.

Administration / exposure

Route of administration:
oral: capsule
Vehicle:
unchanged (no vehicle)
Details on exposure:
Not applicable
Duration and frequency of treatment / exposure:
Single administration
Doses / concentrations
Remarks:
Doses / Concentrations:
Test material equivalent to 50 mg elemental zinc
No. of animals per sex per dose:
Six females and four males
Control animals:
other: not applicable
Positive control:
Not applicable
Details on study design:
No data
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption)
- Tissues and body fluids sampled: Blood
- Time and frequency of sampling: Two samples (15 min apart) for baseline data at start of study; various samples at 30 min and thereafter at hourly intervals for 5 h after drug administration.

Statistics:
Crunch version 3.0 was used for the statistical analysis of variance.

Results and discussion

Preliminary studies:
Not performed

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Zinc was least absorbed after oral administration of zinc oxide among all the zinc compounds tested. Peak plasma concentration of 159.3 ± 29.5 µg/dL reached after 2.5 hr of zinc oxide administration. Plasma concentration reached the near baseline value after 4.5 hr. (see table 1 for details).
Area under the curve generated by percent changes in plasma zinc was lowest (~ 500) after zinc oxide administration among all the zinc compounds tested (Refer Fig. 3 of the reference).
Refer to Fig. 1 and Fig. 2 of the reference for the time related changes in plasma zinc levels and percent changes in plasma zinc, respectively.
Details on distribution in tissues:
Not performed
Details on excretion:
Not performed
Toxicokinetic parametersopen allclose all
Test no.:
#1
Toxicokinetic parameters:
Cmax: 159.3 ± 29 µg/dL
Test no.:
#1
Toxicokinetic parameters:
Tmax: 2.5 h
Test no.:
#1
Toxicokinetic parameters:
AUC: ca. 500 ( for percent change in plasma zinc)

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
Not applicable

Any other information on results incl. tables

Table 1. Changes in plasma zinc levels following the oral zinc oxide administration

Time point

Plasma Zinc (µg/dL) (mean±SD)

Base I

113.0 ± 22.0

Base II

105.3 ± 18.8

After Zn administration

 

30 min

112.9 ± 20.7

1 h 30 min

143.4 ± 43.6

2 h 30 min

159.3 ± 29.5

3 h 30 min

126.3 ± 25.9

4 h 30 min

113.9 ± 29.8

5 h 30 min

98.4 ± 23.1

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: Least absorption of zinc after zinc oxide administration
Under the study conditions, zinc oxide was least absorbed among all the zinc compounds tested. A comparison of AUC values for different zinc forms were compared, it appeared that the bioavailability of zinc oxide was about 60% of the bioavailability of the soluble forms.
Executive summary:

Oral zinc tolerance test was performed in humans to study the absorption of zinc from various zinc compounds including zinc oxide.

Six female and four male volunteers were administered orally a zinc compound capsule containing 50 mg elemental zinc. Two blood samples were drawn (15 min. apart) for baseline data at initiation of study. Further samples were drawn at 30 min. and thereafter at hourly intervals for 5 h after drug administration. Various zinc compounds (zinc acetate, zinc oxide, zinc sulfate, zinc aminoate and zinc methionine) were tested as described at same dose level in same individuals after every 2 wk intervals.

Zinc was least absorbed after oral administration of zinc oxide among all the zinc compounds tested. Peak plasma concentration of 159.3 ± 29.5 µg/dL reached after 2.5 h of zinc oxide administration. Plasma concentration reached the near baseline value after 4.5 h. Area under the curve generated by percent changes in plasma zinc was lowest (~ 500) after zinc oxide administration among all the zinc compounds tested. A comparison of AUC values for different zinc forms were compared, it appeared that the bioavailability of zinc oxide was about 60% of the bioavailability of the soluble forms.

Under the study conditions, zinc oxide was least absorbed among all the zinc compounds tested.