Reaction mass of zinc oxide and zinc peroxide

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Used in EU risk assessment for zinc metal. 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:

Changes in dietary zinc and copper affect zinc-status indicators of postmenopausal women, notably, extracellular superoxide dismutase and amyloid precursor proteins

Author:

Davis CD, Milne DB & Nielsen FH

Year:

2000

Bibliographic source:

Am. J. Clin. Nutr. 71: 781–8

Materials and methods

Study type:

study with volunteers

Endpoint addressed:

repeated dose toxicity: oral

Principles of method if other than guideline:

Controlled metabolic ward study was performed to evaluate the effect of dietary zinc (and its relation to copper intake) on various indicators of zinc status in humans.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Zinc

EC Number:

231-175-3

EC Name:

Zinc

Cas Number:

7440-66-6

Molecular formula:

Zn

IUPAC Name:

zinc

Constituent 2

Reference substance name:

Reference substance 001

Details on test material:

- Name of test material (as cited in study report): Zinc gluconate

Method

Type of population:

general

Subjects:

- Number of subjects exposed: 25
- Sex: Female (postmenopausal)
- Age: 64.9 ± 6.7 yr
- Race: White
- Weight: 65.1 ± 9.5 kg
- Height: 159.6 ± 7.6 cm
- Known diseases: No underlying disease

Ethical approval:

confirmed and informed consent free of coercion received

Route of exposure:

oral

Reason of exposure:

intentional

Exposure assessment:

measured

Details on exposure:

After a 10 d equilibration period, volunteers divided randomly into two groups and consumed a diet with either a low (1 mg/d; n = 12) or a high (3 mg/d; n = 13) copper content based on a total energy content of 8.4 MJ. They received the same amount of copper throughout the study. Both groups were fed the basal diet (3 mg Zn/d) with no zinc supplement for one 90 d period, and after second 10 d equilibration period, the diet supplemented with 50 mg Zn/d for another 90 d period.

Examinations:

- Zinc concentrations of plasma and blood cellular components
- Plasma, erythrocyte and bone-specific alkaline phosphatase activity
- 5'-Nucleotidase activity in plasma, mononuclear cells, and erythrocytes
- Free and total triiodothyronine, free and total thyroxine, and thyroid-stimulating hormone (TSH) level as a measure of thyroid status
- Superoxide dismutase activity in erythrocytes and serum
- Amyloid precursor protein (APP) expression in platelets
- Ethanol tolerance test to determine effect of zinc intake on ethanol metabolism

All the analysis were performed during the last month of each dietary period.

Medical treatment:

None

Results and discussion

Clinical signs:

No data

Results of examinations:

- Zinc concentrations: Plasma zinc concentrations were within the normal range for healthy adults (10.7–18.4 mmol/L) throughout the low-zinc
period. In contrast, levels were significantly elevated beginning 1 month after zinc supplementation and remained elevated throughout the zinc supplementation period. 8 of 23 volunteers had plasma zinc concentrations > 18.4 mmol/L at the end of the zinc-supplementation period. Neither erythrocyte nor erythrocyte membrane zinc concentrations responded significantly to changes in dietary zinc.

- Alkaline phosphatase activity: Zinc supplementation significantly increased bone-specific alkaline phosphatase activity (0.40 ± 0.02 compared with 0.32 ± 0.02 µkat/L) and seemed to increase plasma alkaline phosphatase activity (1.66 ± 0.02 compared with 1.57 ± 0.02 µkat/L); however, this difference was not significant. Erythrocyte membrane alkaline phosphatase activity did not change significantly with the different dietary treatments.

- 5'-Nucleotidase activity: Zinc supplementation significantly increased mononuclear white cell 5'-nucleotidase activity (17.90 ± 1.54 compared with 12.16 ± 1.54 U/L) (apparent only for high-copper diet group) and significantly decreased plasma 5'-nucleotidase activity (4.64 ± 0.19 compared with 6.36 ± 0.19 U/L). No change in red blood cell membrane activity.

- Thyroid status: Plasma free thyroxine concentrations were significantly higher and plasma free triiodothyronine concentrations tended to be higher, but not significantly so, during the high-zinc period than during the low-zinc period. However, dietary zinc did not significantly affect total thyroxine or triiodothyronine concentrations.

(See Table 2 in attached full study report for details of all the above mentioned parameters)

- Superoxide dismutase activity: Extracellular, but not erythrocyte, superoxide dismutase activity was significantly increased by zinc supplementation. This effect was more apparent when subjects were fed the low-copper diet. In contrast, zinc supplementation depressed erythrocyte superoxide dismutase activity (see Fig 1 in attached full study report).

- APP expression: Zinc supplementation significantly depressed platelet APP expression only when subjects were fed the low-copper diet (see Fig 2 in attached full study report).

- Ethanol tolerance test: Ethanol metabolism was not significantly affected by zinc intake. There were no significant differences in the rate of clearance of ethanol or in alcohol dehydrogenase activity among the different dietary treatments (see Fig 3 in attached full study report).

Effectivity of medical treatment:

Not applicable

Outcome of incidence:

Not applicable

Any other information on results incl. tables

Remarks on thestudy, reported by Davis et al. (2000) and Milne et al. (2001):

From personal communication with the authors it appears that for ESOD activity the initial equilibration values varied markedly between individuals, and that for women who were assigned to the low copper group ESOD activity was substantially higher than for those assigned to the high copper group. This implicates that for this indicator, the assignment of the subjects to the two groups was suboptimal, which might also be the case for other indicators.

The frequent blood sampling (an average of no more than 235 ml per month was drawn) might have compromised the physiology of the subjects (as was suggested for haemoglobin).

The subjects served as their own controls: values upon both treatments (i.e. low and high zinc administration) were compared with values upon first equilibration. However, as the second treatment is not independent of the first treatment, the study design is not optimal.

 

Applicant's summary and conclusion

Conclusions:

In conclusion, changes in dietary zinc and copper affect zinc-status indicators of postmenopausal women, notably, extracellular superoxide dismutase and amyloid precursor proteins.

Executive summary:

Controlled metabolic ward study was performed to evaluate the effect of dietary zinc (and its relation to copper intake) on various indicators of zinc status in humans.

 

Indicators of zinc status were measured in 25 healthy postmenopausal women aged 64.9 ± 6.7 y. After a 10 d equilibration period, volunteers consumed a diet with either a low (1 mg/d; n = 12) or a high (3 mg/d; n = 13) copper content based on a total energy content of 8.4 MJ. They received the same amount of copper throughout the study. Both groups were fed the basal diet (3 mg Zn/d) with no zinc supplement for one 90-d period, and the diet supplemented with 50 mg Zn/d for another 90 d period.

Zinc supplementation significantly increased extracellular but not erythrocyte superoxide dismutase activity. This increase was more apparent when subjects were fed the low copper diet. Zinc supplementation in combination with the low copper diet significantly decreased amyloid precursor protein expression in platelets. Other indicators of zinc status that were significantly elevated after zinc supplementation were as follows: plasma zinc, and free thyroxine concentrations and mononuclear 5'-nucleotidase (only apparent with high copper-diet), and bone-specific alkaline phosphatase activities.

 

In conclusion, changes in dietary zinc and copper affect zinc-status indicators of postmenopausal women, notably, extracellular superoxide dismutase and amyloid precursor proteins.