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Administrative data

Description of key information

No adequate experimental animal studies are available to evaluate the carcinogenicity of zinc compounds in humans.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: oral
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.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Carcinogenic potential of the test material added in drinking water was evaluated in mice in a one year study.
GLP compliance:
not specified
Species:
mouse
Strain:
other: Chester Beatty stock
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Newly-born litters
- Housing: 4-6 per metal cage
- Diet: Basic diet (prepared from a meal-mix supplied by Messrs. Dixon, of Ware, Herts., to which "Bemax" stabilised wheat germ (Vitamins Ltd., Crawley, Sussex), arachis oil (British Pharmacopoeia Standard, from Savory and Moore Ltd., London) and Vitamin A and D concentrates (British Drug Houses Ltd., Poole, Dorset) were added.
The basic diet had the following percentage composition: meal-mix (wheat flour, 68.7; casein, 11.4; milk powder, 8.0; chalk, 1.3; salt mixture, 0.8; andyeast, 2.3); "Bemax" stabilised wheat germ containing carbohydrates, protein, B vitamins, manganese, iron, copper, essential amino acids, 2.5; arachisoil and vitamins A (40,000 I.U.) and D (4,000 I.U.) concentrate 5.0.
Route of administration:
oral: drinking water
Type of inhalation exposure (if applicable):
other: Not applicable
Vehicle:
water
Details on exposure:
VEHICLE
- Concentration in vehicle: 22 g/L and 4.4 g/L
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Not applicable
Duration of treatment / exposure:
1 year
Frequency of treatment:
Daily
Post exposure period:
No
Remarks:
Doses / Concentrations:
22 g/L (5000 ppm zinc)
Basis:
nominal in water
Remarks:
Doses / Concentrations:
4.4 g/L (1000 ppm zinc)
Basis:
nominal in water
No. of animals per sex per dose:
No data
Control animals:
yes, concurrent vehicle
Details on study design:
No data
Positive control:
No data
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Once a wk throughout the experiment and daily when fed


BODY WEIGHT: Yes
- Time schedule for examinations: Once in 2 wk


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No


OPHTHALMOSCOPIC EXAMINATION: No


HAEMATOLOGY: No


CLINICAL CHEMISTRY: No


URINALYSIS: No


NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes, lesions were examined histopathologically. Stomachs were fixed with formol saline and examined for tumours and other changes in the forestomach and glandular epithelium.
Other examinations:
None
Statistics:
No data
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
no effects observed
Details on results:
BODY WEIGHT AND WEIGHT GAIN: No appreciable difference was observed between the treatment and control groups.

HISTOPATHOLOGY: NON-NEOPLASTIC
There were no difference between the treated groups and control regarding the incidence of forestomach epithelial hyperplasia.

HISTOPATHOLOGY: NEOPLASTIC
Incidences of hepatoma, malignant lymphoma and long adenoma observed in the treated mice were similar to the control groups. There were no sex difference between the incidence of tumour observed in the treated groups.
Relevance of carcinogenic effects / potential:
No differences in carcinogenic effects were observed between treatment and control groups under the test conditions.
Dose descriptor:
NOAEL
Effect level:
> 22 000 mg/L drinking water
Sex:
male/female
Basis for effect level:
other: overall effects
Remarks on result:
other: Effect type: carcinogenicity (migrated information)

Table 1: Incidence and types of tumours in mice surviving 45 wk of treatments

Group No. of mice killed during weeks 45-53 No. of mice with
Hepatoma Malignant lymphoma Lung adenoma
22 g ZnSO4/L (5000 ppm Zn) 22 3 2 5
4.4 g ZnSO4/L (1000 ppm Zn) 28 3 4 9
Control 19 1 2 8
5 2 1 2
Conclusions:
Under the test conditions, the test material was found to be non-carcinogenic in mice.
Executive summary:

A study of one-year duration was conducted to evaluate the carcinogenic potential of the test material in mice.

Chester Beatty stock mice (newly-born litters) were used. They were housed in the metal cages (4-6 per cage). The doses of zinc sulphate were 22 g/L (5,000 ppm zinc) and 4.4 g/L (1,000 ppm zinc) in drinking water along with a control group fed a basal diet and normal drinking water. The animals were examined thoroughly once a wk throughout the experiment and daily when fed. Weighing was done once every 2 wk. Deaths of animals occurred during the first 8 wk of experiment due to an epizootic of ectromelia. The survivors were vaccinated with sheep lymph and animals showing a negative or accelerated response were sacrificed. New group of weanling mice (4 -5 wk old) were added to supplement the control group. All the surviving animals were sacrificed after 1 year of treatment and examined for gross pathology. Histopathological examination was done for suspected neoplastic lesions. Stomachs were examined for tumours and other changes in the forestomach and glandular epithelium.

No differences in carcinogenic effects were observed between treatment and control groups under the test conditions.

Under the test conditions, the test material was found to be non-carcinogenic in mice.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Study duration:
chronic
Species:
mouse

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are a range of epidemiological studies that investigated the association between zinc exposure either through occupational activities or food supplementation and increased cancer risks. While no associations were found between occupational zinc exposure and excess cancer risk, the main association that has been made in this context is related to dietary/supplemental zinc and prostate cancer risk.

In contrast to established clinical and experimental evidence that prostate cancer is associated with a decrease in the zinc uptake, numerous epidemiology studies and reports of the effect of dietary and supplemental zinc on the incidence of prostated cancer have provided divergent, inconsistent and inconclusive results which range from adverse effects of zinc, protective effects of zinc and no effect of zinc on the risk of prostate cancer. Clinical and experimental studies have established that zinc levels are decreased in prostate cancer and support a role of zinc as a tumor suppressor agent. Malignant prostate cellsin situare incapable of accumulating high zinc levels from circulation (Franklinet al.,2005; Costello and Franklin, 2006; Franklin and Costello, 2007).

In a recent critical assessment of epidemiology studies regarding dietary/supplemental zinc and prostate cancer risk, Costello et al.,concluded that epidemiological studies have not provided an established relationship for any effect or lack thereof of dietary/supplemental zinc on the risk of prostate cancer. Proclamations of an association of dietary/supplemental zinc and increased prostate cancer are based on inconclusive and uncorroborated reports (Costello et al.,2007).


Justification for selection of carcinogenicity via oral route endpoint:
only 1 key experimental animal study available but several epidemiological studies regarding dietary/supplental zinc and prostated cancer are available, however, not providing an established association of dietary/supplemental zinc and increased prostate cancer

Justification for selection of carcinogenicity via inhalation route endpoint:
no experimental animal study available but several epidemiological studies indicating no association between occupational zinc exposure and excess cancer risk

Carcinogenicity: via oral route (target organ): digestive: stomach; urogenital: prostate

Carcinogenicity: via inhalation route (target organ): respiratory: lung

Justification for classification or non-classification

On the basis of the existing information it can be concluded that there is no conclusive evidence for carcinogenic activity of any of the zinc compounds considered in this chemical safety report.