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Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
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
Objective of study:
absorption
distribution
other: Clearance
Qualifier:
no guideline followed
Principles of method if other than guideline:
Mice were gavaged with test material solution, 8.6-19.3 kBq per mouse, and the whole-body retention and organ content of test material were measured at different times after administration. The age-dependence of the fractional absorption of test material from the gastrointestinal tract (f1), the endogenous faecal excretion fraction of test material (EFEF), tissue distribution and whole-body retention were determined.
GLP compliance:
no
Radiolabelling:
yes
Species:
mouse
Strain:
other: LACA mouse
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Animal Centre, Department of Radiotoxicology, Institute of Radiation Medicine, 27 Tai Ping Road, Beijing 100850, China
- Age at study initiation: Sucklings: 1-20 d; Adolescents: 20-70 d; Young adults: 70-100 d; Adults: 100+ d
- Weight at study initiation: Sucklings: 1·4±0·3 g; Adolescents: 9·2± 1.1 g; Young adults: 17·6±0·6 g; Adults: 19·2±2·1 g
- Housing: Plastic cages with stainless-steel lids with precautions to minimize trace element contamination.
- Individual metabolism cages: Yes, 6 animals from each group
- Diet: Semi-synthetic diet, containing 36·67±0·04 mg zinc/kg, determined by atomic absorption spectrometry (For details of composition of diet see attached pdf, Table 2, Pg 909)
- Water: Distilled deionised water
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature: 23±1 °C
- Humidity: 45-50 %
Route of administration:
other: oral (gavage) and intraperitoneal
Vehicle:
other: sodium acetate buffer (50 mM, pH: 5.6)
Details on exposure:
ORAL EXPOSURE: Not reported
VEHICLE
- Justification for use and choice of vehicle (if other than water): Not available
- Amount of vehicle (if gavage): 0.5 mL of 19.3 kBq (for all other age groups), 0.01 mL of 8.6 kBq (for sucklings)
- pH: 5.6

INTRAPERITONEAL EXPOSURE: Not reported


Duration and frequency of treatment / exposure:
Single dose
Remarks:
Doses / Concentrations:
(a) Oral exposure: 8.6 kBq (sucklings) and 19.3 kBq (adolescent, young adults and adults) (For details see study report, Table 1, Pg 908)
(b) Intraperitoneal exposure: 19·3 kBq (for all other age groups except sucklings)
No. of animals per sex per dose / concentration:
6 females per age group (For details see study report, Table 1, Pg 908)
Control animals:
no
Positive control reference chemical:
No
Details on study design:
- Dose selection rationale: Not reported
- Rationale for animal assignment (if not random): According to their stage of development
- Sacrifice of animals: 2 h to 85 d after gavage
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, clearance)
- Absorption:
- Tissues and body fluids sampled (for absorption): urine, faeces
- Time and frequency of sampling: 2 d after gavage
- Distribution:
- Tissues, organs and body fluids sampled: Liver, spleen, heart, lung, kidneys, femora, quadriceps muscle and blood
Time and frequency of sampling: 1 d after gavage
- Method of analysis: Radioactivity was counted using NaI (TI) detector
- Counting efficiency: 14·3±0·05 %

Statistics:
Statistical analysis of the data was carried out using an unpaired Student's t-test.
Details on absorption:
Gastrointestinal tract absorption fraction: The f1 value significantly decreased with increasing age (see study report, Table 4, Pg 910).
Details on distribution in tissues:
Zinc accumulated in the liver, spleen, kidneys, heart, lungs, femora and quadriceps muscle in all groups of mice. Deposition in the lung, quadriceps muscle and femora decreased with increasing age. See study report, Table 5, pg 910.
The whole body, liver and femur doses absorbed from internally contaminated test material, measured at 20 d after gavage in mice at different ages indicated: 64, 3.2, 2.3 times larger whole body dose, in groups of age 1, 20, 70 d than that in the groups of age 100 d, and the liver and femur doses were 0-2 orders greater than those in the group of age 100 d. See study report, Table 9 and 10, pg 913-914.
Key result
Transfer type:
other: not determined
Observation:
not determined
Details on excretion:
Not applicable
Key result
Toxicokinetic parameters:
half-life 1st: 0.3, 0.1 and 0.3 at age 20, 70 and 100 d respectively
Key result
Toxicokinetic parameters:
half-life 2nd: 3.2, 3.1, 4.1 and 18.6 at age 1, 20, 70 and 100 d respectively
Key result
Toxicokinetic parameters:
half-life 3rd: 8.7, 42.2, 24.8 and 96.7 at age 1, 20, 70 and 100 d respectively
Metabolites identified:
not measured
Details on metabolites:
Not applicable

Endogenous faecal excretion fraction (EFEF): EFEF of test material over 2 d after intraperitoneal injection, significantly increased with increasing age and the EFEF values were 0·083±0·008, 0·099±0·004, 0·122±0·018 and 0·144±0·005 in suckling, adolescent, young adult and older mice respectively.

(see attached study report, Table 3, Pg 910)

Clearance from whole body:

- The metabolic parameters of test material in the organs and tissues of mice of different ages showed no difference in terms of fractions cleared and biological half-lives observed between groups of ages 20 and 70 d.

- The relative fractions of test material (a2) in spleen, kidney and heart decreased significantly with increasing age (p< 0.01).

- The second biological half-life (T2) increased significantly with increasing age in blood, liver, spleen, heart, lungs and muscle of quadriceps femoris; and no difference in T2 was observed among groups of age 1, 20 and 70 d, although in the three groups both T1 and T2 were faster than that in the group of age 100 days. See attached study report, Table 6, 7 and 8, pg 911-913

Conclusions:
Under the conditions of the test, in mice of different ages, the endogenous excretion, fractional intestinal absorption, distribution and clearance of gavaged test material were found to be dependent on age.
Executive summary:

A study was conducted to evaluate the absorption, distribution and clearance of test material in the LACA mice. No guideline or GLP was reported.

Mice were gavaged with test material solution, 8.6-19.3 kBq per mouse, and the whole-body retention and organ content of test material were measured at different times after administration. The age-dependence of the fractional absorption of test material from the gastrointestinal tract (f1), the endogenous faecal excretion fraction of test material (EFEF), tissue distribution and whole-body retention were determined.

The f1 values obtained were 0.86±0.15, 0.64±0.11, 0.52±0.07 and 0.39±0.02 in suckling, adolescent, young adult and older mice, respectively. The EFEF values determined were 0·083±0·008, 0·099±0·004, 0·122±0·018 and 0·144±0·005 of intraperitoneally injected test material in suckling, adolescent, young adult and older mice respectively at administration.

Test material mainly distributed in the liver, muscle, lung, kidneys and bone. In some tissues, there was an inverse relationship between the relative content of gavaged test material and the animal's age at administration. The whole-body biological half-lives of zinc-65 increased with animal age.

Hence, under the conditions of the test, in mice of different ages, the endogenous excretion, fractional intestinal absorption, distribution and clearance of gavaged test material were found to be dependent on age (He, 1991).

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
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
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
Radiolabelling:
yes
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)
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
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
Preliminary studies:
Not applicable
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
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
Metabolites identified:
not measured
Details on metabolites:
Not applicable

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.

Conclusions:
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 Zn65 Cl 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 Zn65 Cl 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 (Furchner, 1962).

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
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.
Objective of study:
absorption
excretion
Principles of method if other than guideline:
Zinc absorption and excretion in Wistar rats from 65Zn-Zinc chloride was measured.
GLP compliance:
no
Radiolabelling:
yes
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: Adult
- Weight at study initiation: 250.1 ± 3.1 g
- Fasting period before study: Overnight
- Housing: Individually in polypropylene cages with stainless steel gridded tops and bottoms
- Individual metabolism cages: No
- Diet (e.g. ad libitum): SS control diet (containing FeSO4.7H2O, 174 mg/kg diet equivalent to Fe added at 35 mg/kg), ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 °C
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: feed
Vehicle:
other: cooked starch-sucrose water (1:1:6) paste
Details on exposure:
DIET PREPARATION
- Mixing appropriate amounts with (Type of food): 5 g meal of cooked starch-sucrose water (1:1:6) paste containing 130 µg Zn as ZnCl2 extrinsically labelled with 37 kBq 65Zn (ZnCI2, 3.7-92.5 MBq/mg Zn); given to rats for 1 h
- SS control diet, ad libitum was provided 6 h after consumption of the test meal
Duration and frequency of treatment / exposure:
Single exposure, rats were allowed to consume the test meal for 1 h
Remarks:
Doses / Concentrations:
130 µg Zn as 65Zn-Zinc chloride
No. of animals per sex per dose / concentration:
15
Control animals:
no
Positive control reference chemical:
No
Details on study design:
- Animal assignment: Random
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, excretion)
- Tissues and body fluids sampled (delete / add / specify): Whole body and faeces
- Time and frequency of sampling: Whole body counted immediately after consuming the meal (Day 0) and then again each day until the end of the experiment (Day 14). Faeces were collected from Day 0 to Day 4, pooled for each rat, and counted for 65Zn.
- Method type(s) for identification: Whole-body radioactivity was measured using an NE 8112 small-animal whole-body gamma counter (NE Technology, Beenham, Berkshire, UK)
Statistics:
F-test (when the variances differed significantly); t-test (where the variance ratio showed a treatment effect)
Type:
absorption
Results:
65Zn absorption (%) = 45.1 ± 2.1
Type:
excretion
Results:
Fractional rate of 65Zn loss/day = 0.0171 ± 0.0006
Details on absorption:
65Zn absorption (%) = 45.1 ± 2.1
Details on distribution in tissues:
Not determined
Key result
Observation:
not determined
Details on excretion:
Fractional rate of 65Zn loss/day = 0.0171 ± 0.0006
Key result
Toxicokinetic parameters:
other: Not applicable
Metabolites identified:
not measured
Details on metabolites:
Not applicable

Experiment 2: Data obtained from the experiment indicated that the availability of Zinc from Zn5(OH)8CI2.H2O was similar to that from ZnCO3 and ZnCI2, and hence, the basic Zinc salt is of high bioavailability. The availability of iron from the basic iron salts, however, was very poor when compared to ferrous sulphate.

Conclusions:
Under the test conditions, the test material was determined to possess high bioavailability. 65Zn absorption (%) and fractional rate of 65Zn loss/day from the radiolabelled test material were determined to be 45.1 ± 2.1 and 0.0171 ± 0.0006, respectively.
Executive summary:

A study was conducted to determine the oral absorption and excretion of Zinc in Wistar rats administered with diet containing 130 µg Zn as ZnCl2 extrinsically labelled with 37 kBq Zn65 (ZnCI2, 3.7-92.5 MBq/mg Zn). Rats were allowed to consume the test meal for 1 h, and immediately after consuming the meal (Day 0) and then again each day until the end of the experiment (Day 14), whole-body radioactivity was measured using gamma counter. Under the test conditions, the test material was determined to possess high bioavailability. Zn65 absorption (%) and fractional rate of Zn65 loss/day from the radiolabelled test material were determined to be 45.1 ± 2.1 and 0.0171 ± 0.0006, respectively. However, it must be noted that in this study other zinc compounds were tested and no distinction was made between the different zinc compounds during the observations (Galvez-Morros, 1991).

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
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
Remarks:
Used in risk assessment report for zinc chloride, acceptable for assessment
Objective of study:
distribution
Principles of method if other than guideline:
The tissue uptake of 65Zn2+ (as zinc chloride) was determined in adult male Wistar rats after intraperitoneal injection of 15 µCi 65Zn2+.
GLP compliance:
not specified
Radiolabelling:
not specified
Species:
rat
Strain:
Wistar
Sex:
male
Route of administration:
intraperitoneal
Vehicle:
not specified
Duration and frequency of treatment / exposure:
No data
Remarks:
Doses / Concentrations:
15 µCi 65Zn2+
No. of animals per sex per dose / concentration:
No data
Control animals:
not specified
Preliminary studies:
Not applicable
Type:
distribution
Results:
The liver displayed the greatest uptake for zinc ions, followed by the kidney, pancreas, spleen, ileum, lung, heart, bone, testis, blood cells, muscle and brain.
Details on absorption:
Not applicable
Details on distribution in tissues:
The liver displayed the greatest uptake for zinc ions, followed by the kidney, pancreas, spleen, ileum, lung, heart, bone, testis, blood cells, muscle and brain. Additional data on Zn2+ uptake by the brain indicate that the blood-brain barrier is minimally permeable to zinc cations.
Key result
Transfer type:
other: Not reported
Details on excretion:
Not applicable
Key result
Toxicokinetic parameters:
other: Not applicable
Metabolites identified:
not measured
Details on metabolites:
Not applicable
Conclusions:
The liver displayed the greatest uptake for zinc ions, followed by the kidney, pancreas, spleen, ileum, lung, heart, bone, testis, blood cells, muscle and brain.
Executive summary:

The tissue uptake of 65Zn2+ (as zinc chloride) was determined in adult male Wistar rats after intraperitoneal injection of 15 µCi 65Zn2+.

The liver displayed the greatest uptake for zinc ions, followed by the kidney, pancreas, spleen, ileum, lung, heart, bone, testis, blood cells, muscle and brain. Additional data on Zn2+ uptake by the brain indicate that the blood-brain barrier is minimally permeable to zinc cations (Pullen, 1990).

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting 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
Objective of study:
distribution
Qualifier:
no guideline followed
Principles of method if other than guideline:
Distribution of zinc to different organs measured for up to 14 d after single oral administration of radiolabelled zinc chloride to male Wistar rats.
GLP compliance:
not specified
Radiolabelling:
yes
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 240 g
- Diet: Granulated feed supplied by Bacutil and supplemented with white bred, milk and carrot.

Route of administration:
oral: gavage
Vehicle:
not specified
Duration and frequency of treatment / exposure:
Single administration
Remarks:
Doses / Concentrations:
0.1 µCi (3.7 kBq) of Zn (65)
No. of animals per sex per dose / concentration:
30
Control animals:
other: not applicable
Positive control reference chemical:
Not applicable
Details on study design:
No data
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Distribution)
- Tissues and body fluids sampled: Stomach, small intestine, large intestine without its contents, liver, kidneys, lungs, spleen, testicle, prostate, brain, blood, heart, thigh muscles and hairs.
- Time and frequency of sampling: After 6 and 24 h and after 2, 4, 7, 14 d from the administration of radioisotope.
- Other: To avoid any losses of Zn (65), radioactivity of 1 g of each sample (1 mL of blood , whole heart, spleen and prostate) was immediately measured.


Statistics:
Student's t test
Preliminary studies:
Not performed
Type:
distribution
Results:
Highest accumulation in small intestine, liver, kidneys and large intestine; smaller amount in lungs and spleen; smallest amounts at nearly same level in brain, prostate, heart, blood, skin, hairs and gonads.
Details on absorption:
Not measured
Details on distribution in tissues:
Highest accumulation in small intestine, liver, kidneys and large intestine; smaller amount in lungs and spleen; smallest amounts at nearly same level in brain, prostate, heart, blood, skin, hairs and gonads.
Details on excretion:
Not measured
Metabolites identified:
not measured
Details on metabolites:
Not applicable
Conclusions:
In conclusion, zinc was mainly accumulated in small intestine, liver, kidneys and large intestine after single oral administration of zinc chloride to male Wistar rats.
Executive summary:

A study was conducted to determine the distribution of zinc to different organs after oral administration of zinc chloride in rats.

30 male Wistar rats were intubated with 0.1 µCi (3.7 kBq) 65Zn as zinc chloride. Animals were sacrificed after 6 and 24 h and after 2, 4, 7, 14 d of administration and various organs viz. stomach, small intestine, large intestine without its contents, liver, kidneys, spleen, testicle, prostate, brain, blood, heart, thigh muscles and hairs were analysed for zinc concentration.

Zinc was accumulated in the highest amount within the small intestine, liver, kidneys and large intestine and in smaller amounts in lungs and spleen. The smallest amounts were found at nearly same level in brain, prostate, heart, blood, skin, hairs and gonads.

In conclusion, zinc was mainly accumulated in small intestine, liver, kidneys and large intestine after single oral administration of zinc chloride (Kossakowski, 1983).

Description of key information

Key value for chemical safety assessment

Absorption rate - oral (%):
20
Absorption rate - dermal (%):
2
Absorption rate - inhalation (%):
40

Additional information

Under physiological conditions, zinc diacrylate dissociates rapidly and completely into zinc and acrylic acid. Systemic toxicity will mainly be driven by zinc rather than acrylic acid, therefore the following discussion on toxicokinetics focuses on this constituent.

 

Toxicokinetic testing was conducted with various zinc compounds which release, depending on their solubility, zinc cations. Data is available on soluble zinc compounds (zinc chloride and zinc sulphate) and on slightly soluble zinc compounds (ZnO and ZnCO3).

 

Oral

Zinc is an essential trace element which is regulated and maintained in the various tissues mainly by the gastrointestinal absorption and secretion during high and low dietary zinc intake and because of the limited exchange of zinc between tissues, a constant supply of zinc is required to sustain the physiological requirements. The zinc absorption process in the intestines includes both passive diffusion and a carrier-mediated process. The absorption can be influenced by several factors such as ligands in the diet and the zinc status. Persons with adequate nutritional levels absorb 20-30% and animals absorb 40-50%. Persons that are zinc deficient absorb more, while persons with excessive zinc intake absorb less.

For the soluble zinc compounds, the available information suggests an oral absorption value of 20%. This value can be considered as the lower bound range at adequate nutritional levels. The oral absorption of the slightly soluble zinc oxide has been shown to be 60% of that of the soluble zinc compounds. This corresponds to approximately 12-18%. No oral absorption information is available for the remaining slightly soluble and insoluble zinc compounds (i.e. Zn(OH)2, Zn3(PO4)2, ZnCO3, Zn, ZnS). However, considering that these substances have lower water solubility than ZnO, it can be conservatively assumed that the oral absorption of these compounds is ≤ 12%.

 

Inhalation

Animal data suggests that there is pulmonary absorption following inhalation exposure. Half-life values of 14 and 6.3 hours were reported for dissolution of zinc oxide. The absorption of inhaled zinc depends on the particle size and the deposition of these particles therefore data was provided on the particle size distribution of zinc aerosol from three different industry sectors. The particle size distribution data was evaluated by using a multiple path particle deposition (MPPD) model. This model revealed that for zinc aerosols the largest part of the deposition is in the head region and much less in the tracheobronchial and pulmonary region. Although most of the material deposited in the head and tracheobronchial region is rapidly translocated to the gastrointestinal tract, a part will also be absorbed locally.

Based on data for local absorption of radionuclides in the different airway regions, it can be assumed that the local absorption of the soluble zinc compounds will be approximately 20% of the material deposited in the head region, 50% of the material deposited in the tracheobronchial region and 100% of the material deposited in the pulmonary region. For the slightly soluble and insoluble zinc compounds a negligible absorption can be assumed for materials deposited in the head and the tracheobronchial region. 100% of the deposited slightly or insoluble zinc compounds are assumed to be absorbed in the pulmonary tract. The deposited material will be cleared via the lung clearance mechanisms into the gastrointestinal tract where it will follow oral absorption kinetics. Therefore the inhalation absorption for the soluble zinc compounds is a maximum of 40% and for the slightly soluble and insoluble zinc compounds inhalation absorption is at a maximum of 20%. These values can be assumed as a reasonable worst case, because they are considered to cover existing differences between the different zinc industry sectors with respect to the type of exercise activities (and thus breathing rate) and particle size distribution.

 

Dermal

The available information from in vivo as well as the in vitro studies suggests the dermal absorption of zinc compounds through intact skin to be less than 2%. In vitro studies that estimated dermal absorption values only on the basis of the zinc levels in the receptor medium without taking into account the zinc present in the stratum corneum appear to underestimate absorption values derived from in vivo studies. Such zinc trapped in the skin layers may become systemically available at a later stage. Quantitative data to evaluate the relevance of this skin depot are however lacking. Given the efficient homeostatic mechanisms of mammals to maintain the total body zinc and the physiologically required levels of zinc in the various tissues to be constant, the anticipated slow release of zinc from the skin is not expected to disturb the homeostatic zinc balance of the body. Considering the available information on dermal absorption, the default for dermal absorption of all zinc compounds (solutions or suspensions) is 2%. Based on the physical appearance, for dust exposure to zinc and zinc compounds a 10-fold lower default value of 0.2% is a reasonable assumption.

 

Zinc appears to be distributed to all tissues and tissue fluids and it is a cofactor in over 200 enzyme systems. The excretion of zinc is primarily via faeces, but also via urine, saliva, hair loss, sweat and mothers-milk.