Zinc di(acetate)

Carcinogenicity

Description of key information

Carcinogenicity: Supporting information: Results of assays with Zinc Acetate show that the average number of tumors per animal was not significant (related to the control groups). 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity

Remarks:

intraperitoneal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1975

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: No specific test guideline was reported; however, a scientifically defensible approach was used to conduct the study. No GLP.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Animals/dose group: 20 mice (10 females and 10 males. Strain A)
Vehicle: 0.85% NaCl solution
Administration: i. p. injections
Animals are dosed: thrice-weekly (a total of 24 injections)
Positive carcinogen substance used in the study: Urethan
Duration of the study: 30 weeks

GLP compliance:

not specified

Species:

mouse

Strain:

Strain A

Sex:

male/female

Route of administration:

intraperitoneal

Vehicle:

other: 0.85% NaCl solution

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

30 weeks

Frequency of treatment:

24 injections applied thrice-weekly.

Post exposure period:

22 weeks after the last injection all the animals were killed.

Remarks:

Doses / Concentrations:
360 mg/kg bw/day
Basis:
nominal conc.
0.85% NaCl solution

Remarks:

Doses / Concentrations:
180 mg/kg bw/day
Basis:
nominal conc.
0.85% NaCl solution

Remarks:

Doses / Concentrations:
72 mg/kg bw/day
Basis:
nominal conc.
0.85% NaCl solution

No. of animals per sex per dose:

10 females and 10 males per dose.

Control animals:

yes, concurrent no treatment

yes, concurrent vehicle

Positive control:

Urethan

Sacrifice and pathology:

GROSS PATHOLOGY: No data
HISTOPATHOLOGY: Yes

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Relevance of carcinogenic effects / potential:

No tumors other than lung adenomas, 4 thymomas in mice treated, were observed in the controls.
Neoplasmas other than lung tumors were observed in the zinc acetate group.

Dose descriptor:

other: maximum tolerated dose

Effect level:

360 mg/kg bw (total dose)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects

Remarks on result:

other: Effect type: carcinogenicity (migrated information)

No tumors other than lung adenomas were observed in the controls:

Table 1: Lung tumors In vehicle-treated, urethan, and untreated A/Strong mice

Treatment	Duration of experiment (wk)	No. i.p, injections	Survivors/ initial	Mice with lung tumors (%)	Av. no. of tumors/mouse
0.65% NaCl solution	30	24	19/20	37	0,42 ± 0.10^1
Tricaprylin	30	24	18/20	44	0.50 ± 0.12
Urethan 20 mg	30	1	18/20	100	21.6 ± 2.81
Untreated	30	0	19/20	31	0.28 ± 0.07

Mean ± S.E.

Pulmonary tumors in A/strong mice treated with zinc acetate:

Table 2. Pulmonary tumors in A/strong mice treated with zinc acetate

Compound	M.W.	Vehicle"	Duration of experi-ment (wk)	No. of i.p. injec-tions	Total dose (mg/kg of mouse)	No, of ani-mals survi-	Mice with lung tu-mors	Av.no. of lung tumors/mouse	p
Zinc(II) Acetate	219.49	s	30	24	360	16/20	7	0.78 ± 0,22	NS
					160	18/20	8	0.67 ± 0.16	NS
					72	18/20	9	0.67 ± 0.16	NS

^aS: 0.85% NaCl solution ^bMean ± S.E. ^cNS: no significant

Conclusions:

Results of the assay shows that the average number of tumors per mouse induced by Zinc acetate was not significant (related to the control groups).

Executive summary:

The zinc acetate carcinogenicity study was performed with strain A mice.

The results of the 3 dose concentrations tested (360, 180 and 72 mg/kg bw) shown that the average number of tumors per mouse were not significant (related to the control groups).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Supporting information: Experimental data:

In the study reported by Stoner et al. (1976), a carcinogenicity study was performed with Zinc Acetate and strain A mice for 30 weeks. The results of the 3 dose concentrations tested (360, 180 and 72 mg/kg bw) shown that the average number of tumors per mouse were not significant (related to the control groups).

In the study reported by Rath et al. (1989) male and female rats received drinking water enriched with zinc acetate, 22.8 mmol/L, for 14 days. After this time of Zinc acetate exposure, a tumour cell suspension was injected into the tail vein of each of the 30 rats (no in control group). Rats were killed 36 days after the i.v. tumour cell application. The metastases developed in the lungs were counted. In both injected groups, the number of metastases on the surface is significantly correlated with the number of metastases on the cuts. Zinc ions seem to promote the emigration, implantation and outgrowth of circulating tumour cells.

In the control group (animals only treated with zinc-enriched drinking water for 380 days) no tumours were observed. The NOAEL was equal or higher than 5000 mg/L drinking water (for carcinogenicity).