Fatty acids, C16-18, zinc salts

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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:

study report

Title:

Unnamed

Year:

1989

Materials and methods

Study type:

study with volunteers

Endpoint addressed:

repeated dose toxicity: oral

Principles of method if other than guideline:

A 10-wk single blind study was conducted to determine the response of iron, copper and zinc status to supplementation with oral zinc or a combination of zinc and iron supplementation.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Bis(D-gluconato-O1,O2)zinc

EC Number:

224-736-9

EC Name:

Bis(D-gluconato-O1,O2)zinc

Cas Number:

4468-02-4

IUPAC Name:

zinc bis(2,3,4,5,6-pentahydroxyhexanoate) (non-preferred name)

Details on test material:

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

Method

Type of population:

general

Subjects:

- Number of subjects exposed: 18
- Sex: Female
- Age: 25-40 yr
- Known diseases: None
- Other: All subjects were judged to be in good health and nutritional status and of acceptable weight for height (information collected through questionnaire).

Ethical approval:

confirmed and informed consent free of coercion received

Route of exposure:

oral

Reason of exposure:

intentional

Exposure assessment:

measured

Details on exposure:

- Study design: Subjects were randomly divided into 2 groups (1) Group Z: Zinc supplemented group and (2) Group F-Z: Zinc and iron supplemented group, blinded to treatment.
- Dose: Group Z: 25 mg Zn in each capsule; Group F-Z: 25 mg each of Fe and Zn
- Frequency of administration: Two gelatin capsules daily (one in the morning and one in the evening)

Examinations:

- Pre-treatment mineral status analysis: Zn, Fe and Cu levels of each subject of both groups were determined before treatment (see Table 1 and 2 in the attached document).
- Blood and saliva samples were analysed for effects of Zinc and Zinc+iron supplementation on Fe, Cu and Zn levels by measuring the following parameters:
- Salivary sediment: Were analysed for Zn content by flame atomic absorption spectrophotometry.
- Whole blood hemoglobin and hematocrit levels - Were analysed for Fe content by cyanmethemoglobin method (Interdepartmental Committee on Nutrition for National Defense. Manual for nutrition surveys, 1963) and microhematocrit by centrifugation (McGovern et al, 1955).
- Erythrocyte superoxide dismutase (ESOD) activity - Were analysed for Cu and Zn content using photochemical o-dianisidine-riboflavin assay (Paynter, 1980; Misra et al, 1977).
- Serum analysis: (a) Serum Zn content - Measured by direct aspiration into the flame with standards prepared in glycerol-water (Smith et al, 1979); (b) Serum ferritin - Measured for Fe content, using the nEIA-ferritin enzyme immunoassay; (c) Serum ceruloplasmin - Measured for Cu content using radial immunodiffusion with the NOR-Partigen ceruloplasmin kit.

Medical treatment:

None

Results and discussion

Clinical signs:

Not examined

Results of examinations:

(A) Effects of Zinc supplementation on Fe, Cu and Zn levels after 6 and 10 wk (Group Z): (See Table 1 in the attached document)
- Both serum ferritin and haematocrit were significantly lower at 10 wk than at pre-treatment (p < 0.05) where as hemoglobin was unchanged.
- For Cu, ESOD levels declined after 6 wk of supplementation and were significantly different (p < 0.0001) from pre-treatment levels at 10 wk. No
change occurred in serum ceruloplasmin levels over the course of treatment.
- Although salivary-sediment Zn levels increased slightly but not significantly with Zn supplementation, serum Zn increased both at 6 and 10 wk
compared with pre-treatment levels (p < 0.01).
(B) Effects of Iron + Zinc supplementation on Fe, Cu and Zn levels after 6 and 10 wk (Group F+Z): (See Table 2 in the attached document)
- For Fe, supplementation resulted in an increase in serum ferritin at 6 and 10 wk compared with pre-treatment levels (p < 0.01). This contrasts
with the decrease seen in serum ferritin in those subjects consuming Zn only. Hemoglobin and hematocrit were unchanged after treatment with
Fe and Zn.
- Changes in Cu status were similar to those occurring in the Zn-supplemented group, with ESOD decreasing (p < 0.0001) and no change in serum ceruloplasmin levels.
- As for Group Z, serum Zn levels in the Fe-Zn supplemented group increased with supplementation (p < 0.05). In contrast, salivary-sediment Zn
levels decreased over the course of the Fe-Zn treatment (p < 0.05).

Effectivity of medical treatment:

Not applicable

Outcome of incidence:

Not applicable

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:

Under the conditions of the test, zinc supplementation significantly lowered iron and copper status, as assessed through serum ferritin, hematocrit and ESOD levels and inclusion of Iron with zinc ameliorates the effect on iron but not on copper status. The NOAEL in this study is less than 0.83 mg Zn2+/kg bw.

Executive summary:

A 10-wk single-blind study was conducted to determine the response of iron, copper and zinc status to supplementation with oral zinc or a combination of zinc and iron supplementation.

18 female volunteers were randomly assigned to the two treatment groups and consuming either 50 mg Zn/d as zinc gluconate (Group Z) or 50 mg Fe as ferrous sulfate monohydrate in addition to the zn (Group F+Z). Blood and saliva samples were analysed for Fe, Cu and zn levels before treatment (pre-treatment) and after 6 and 10 wk of supplementation.

For Group Z, serum ferritin, hematocrit, and erythrocyte Cu and zn-superoxidedismutase (ESOD) were significantly lower (p < 0.05) after 10 wk supplementation compared with pre-treatment levels. Serum zn increased (p < 0.01) but no change occurred in serum ceruloplasmin, hemoglobin, or salivary sediment zn levels. For Group F-Z, ESOD and salivary sediment zn (p < 0.05) decreased with treatment. Serum ferritin and serum zn increased significantly, but hemoglobin, hematocrit, and ceruloplasmin were not affected by the combination treatment.

Under the conditions of the test, zinc supplementation significantly lowered iron and copper status, as assessed through serum ferritin, hematocrit and ESOD levels and inclusion of Iron with Zinc ameliorates the effect on Iron but not on Copper status. The NOAEL in this study is less than 0.83 mg Zn²⁺/kg bw.