Ammonium zinc chloride

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting 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.

Justification for data waiving:

other:

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:

Unnamed

Year:

1992

Materials and methods

Principles of method if other than guideline:

The test material was orally administered to Wistar rats daily for a period of 28 d. Animals were sacrificed after test material treatment to determine hematological indices.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Zinc chloride

EC Number:

231-592-0

EC Name:

Zinc chloride

Cas Number:

7646-85-7

IUPAC Name:

zinc dichloride

Details on test material:

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

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 2 months
- Weight at study initiation: 150-180 g
- Housing: Housed singly in cages
- Diet (e.g. ad libitum): Standard granulated rodent laboratory chow-LSM (CLPP, Motycz near Lublin)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-20
- Humidity (%): 60±10
- Photoperiod (hrs dark / hrs light): Natural day-night light cycles

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on oral exposure:

Not reported

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

Not applicable

Duration of treatment / exposure:

28 d

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0 and 0.12 mg Zn/cm3
Basis:
nominal in water

No. of animals per sex per dose:

Control group: 12 males and 12 females
Treatment group: 13 males and 17 females

Control animals:

yes, concurrent vehicle

Details on study design:

Not reported

Positive control:

Not reported

Examinations

Observations and examinations performed and frequency:

BODY WEIGHT: Yes


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes


HAEMATOLOGY: Yes
- Anaesthetic used for blood collection: Yes (ether)
- How many animals: 13 males and 17 females in treatment group and 12 males and 12 females in control group
- Parameters checked in table [No. 3, 4, 5 and fig. 2] were examined.

Sacrifice and pathology:

Not reported

Other examinations:

None

Statistics:

Students t-test at the significance level P < 0.05

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

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:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY: No mortality observed (For details see table 1)


BODY WEIGHT AND WEIGHT GAIN: Body weight increment of treated animals was similar to that of the controls. (For details see table 1 and fig. 1)


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Statistically significant decrease in food consumption was noted in treated animals as compared to that of the control group. (For detials see table 2)


HAEMATOLOGY: Statistically significant decrease in the erythrocyte count and haemoglobin level was found in the peripheral blood of treated animals. The haematocrit index decreased only slightly. (For details see table 3). Statistically significant increase in leukocyte count was noted in the treated males (For details see table 3). Percentage of reticulocytes and polychromatophilic erythrocytes in the peripheral blood of treated animals increased significantly as compared with that in the controls (For details see fig. 2). No major changes in the percentage composition of bone marrow cells between the control and treated animals observed. (For details see table 5)

Effect levels

Dose descriptor:

other: Significant increase in percentage of reticulocytes and polychromatophilic erythrocytes and statistically significant decrease in the erythrocyte count and haemoglobin level in the peripheral blood observed.

Effect level:

0.12 other: mg Zn/cm3

Sex:

male/female

Basis for effect level:

other: Haematology

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table1: The effect of zinc chloride (ZC) on body weight gain in rats

Group of animals	Initial number of animals	Mortality	Number of animals examined	Body weight gain
Males				g	g/24 h
Control	12	0	12	84.83 ± 6.42	3.03 ± 0.23
ZC	13	0	13	78.81 ± 4.07	2.82 ± 0.14
Females
Control	12	0	12	36.70 ± 2.41	1.32 ± 0.09
ZC	17	0	17	40.53 ± 2.49	1.45 ± 0.09

Table 2: Food, fluid and zinc intake in the studied animal groups

Group of animals	Food intake (g/rat/24 h)	Fluid intake (cm^3/rat/24h)	Zinc (mg/kg body wt/24 h)
Males
Control	27.02 ± 0.64	26.40 ± 0.70	-
ZC	22.97 ± 0.40	19.85 ± 0.46***	11.66 ± 0.61
Females
Control	20.83 ± 0.34	25.20 ± 1.35	-
ZC	19.79 ± 0.27*	18.36 ± 0.85***	12.75 ± 1.09

Table 3: Haematological indices of peripheral blood in the studied animal groups

Group of animals	Erythrocytes x10^12/dm^3	Haemoglobin nmol/L	Haematocrit (I)^a	Leukocytes x 10^9/dm^3
Males
Control	8.25 ± 0.10	9.96 ± 0.22	0.48 ± 0.003	8.73 ± 0.72
ZC	7.67 ± 0.15**	8.79 ± 0.23**	0.46 ± 0.004	12.60 ± 1.09*
Females
Control	8.31 ± 0.09	10.27 ± 0.34	0.48 ± 0.003	8.86 ± 0.65
ZC	7.46 ± 0.15***	8.56 ± 0.24**	0.46 ± 0.005	10.72 ± 0.94

^a unit "one"

Table 4: Leukocyte picture of peripheral blood in rats

Group of animals	Several forms of leukocytes (10^9/dm3
	Neutrophils	Eosinophils	Monocytes	Lymphocytes
Males
Control	1.23 ± 0.20	0.13 ± 0.03	0.35 ± 0.06	7.02 ± 049
ZC	2.40 ± 0.45*	0.12 ± 0.02	0.35 ± 0.05	9.73 ± 0.73**
Females
Control	1.44 ± 0.21	0.17 ± 0.03	0.41 ± 0.06	6.85 ± 0.46
ZC	1.59 ± 0.19	0.21 ± 0.05	0.36 ± 0.04	8.56 ± 0.72

Table 5: % composition of bone marrow cells in the studied animal groups

	Males		Females
Number of animals	Control	ZC	Control	ZC
Proerythroblasts	0.40±0.08	0.35 ± 0.06	0.44 ± 0.07	0.52±0.09
Basophilic erythroblasts	2.98 ± 0.20	2.80 ± 0.02	3.46 ± 0.23	3.25 ± 0.24
Polychroamtophilic eryhtoroblasts	9.81 ± 0.41	9.46 ± 0.35	10.36 ± 0.48	9.97 ± 0.41
Orthochromatic eryhtoroblasts	23.08 ± 0.93	24.51 ± 1.13	24.21 ± 1.08	22.61 ± 0.71
Myeloblasts	2.39 ± 0.19	1.76 ± 0.10*	2.75 ± 0.30	2.30 ± 0.14
Neutrophil granulocytes	29.89 ± 1.01	27.78 ± 1.43	25.78 ± 1.57	28.32 ± 0.84
Eosinophil granulocytes	3.55 ± 0.32	2.95 ± 0.25	5.36 ± 0.75	4.09 ± 0.33
Basophil granulocytes	0.79 ± 0.08	1.08 ± 0.14	0.92 ± 0.12	1.22 ± 0.18
Lymphocytes	18.26 ± 1.06	20.37 ± 2.19	18.33 ±0.90	19.26 ± 0.88
Monocytes	2.12 ± 0.13	2.34 ± 0.17	1.94 ± 0.12	2.09 ± 0.12
Plasma cells	0.40 ± 0.09	0.41± 0.07	0.52 ± 0.09	0.36 ± 0.06
Reticulum cells	5.72 ± 0.24	5.59 ± 0.23	5.26 ± 0.45	5.44 ± 0.31
Macrophagic reticulum cells	0.53 ± 0.08	0.60 ± 0.08	0.68 ± 0.09	0.56 ± 0.06

Significantly different from control group: *P < 0.05, **P < 0.01, ***P < 0.001

Applicant's summary and conclusion

Conclusions:

Under the conditions of this test, the test material was observed to alter haematological parameters in Wistar rats.

Executive summary:

A study was conducted in Wistar rats to assess the effect of test material on certain haematological parameters.

 

Animals were treated orally at a concentration of 0.12 mg Zn/cm³ daily for 28 d. Significant increase in percentage of recticulocytes and polychromatophilic erythrocytes and statistically significant decrease in the erythrocyte count and haemoglobin level in the peripheral blood was observed. No major changes in the percentage composition of bone marrow cells between the control and treated animals were observed.

 

Under the conditions of this test, the test material was observed to alter haematological parameters in Wistar rats.