Mercury

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study reliable with restrictions

Data source

Reference

Reference Type:

publication

Title:

Combined effects of mercury and hexachlorobenzene in the rat

Author:

Lecavalier, P.R. et al.

Year:

1994

Bibliographic source:

J. Environ. Sci Health, B29(5), 951 - 961.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Groups of 10 female Sprague-Dawley rats received single doses of mercury chloride (10.0 and 12.5 mg/kg b.w. aqueous) by gavage followed by an observation period of 14 days. The surviving animals were necropsied at termination of the study, and hematological, clinical chemistry, histopathological and tissue residue analyses were performed.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Mercury dichloride

EC Number:

231-299-8

EC Name:

Mercury dichloride

Cas Number:

7487-94-7

IUPAC Name:

mercury dichloride

Details on test material:

- Name of test material (as cited in study report): mercury chloride (from Aldrich (Milwaukee, WS)
- Analytical purity: > 99.99 %
- Other: chemical was used without further purification.
No further information on the test material was stated.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Inc., Montreal
- Weight at study initiation: approx. 200 g
- Fasting period before study: overnight fasting
- Housing: individually in stainless-steel mesh cages.
- Acclimation period: one week prior to initiation of the study.
No further information on the test animals was stated.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 0.5 mL/100 g b.w. (0.2 % or 0.25 % W/V)

- RATIONALE FOR THE SELECTION OF FEMALES: female rats were chosen in the present study because there was abundant evidence in the literature to indicate that the female is more sensitive gender towards acute toxicity of most chemicals.
No further information on the oral exposure was stated.

Doses:

0, 10, and 12.5 mg/kg b.w. (Recalculated for mercury (element) by a toxicologist: 7.4 and 9.2 mg/kg Hg, respectively)

No. of animals per sex per dose:

10 female rats

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: animals were observed for signs of toxicity on a hourly basis for the first 36 hours after which time clinical observation, body weight gain and food consumption were determined daily.

- Necropsy of survivors performed: Yes
Fourteen days after treatment the surviving animals were anaesthetized and exsanguinated via the abdominal aorta. All animals were examined fro gross changes at the time of necropsy. The brain, heart, liver, spleen, and kidneys were weighed and fixed in 10 % phosphate buffered formalin for histological examination along with pituitary, adrenal, thyroid, parathyroid, thymus, lungs, trachea, bronchi, thoracic aorta, oesophagus, gastric cardia, gastric fundus, gastric pylorus, duodenum, pancreas, colon, bone marrow, mesenteric lymph nodes, skeletal muscle, salivary glands, skin, peripheral nerve, superior root ganglia, eyes, urinary bladder, uterus and ovaries.

- Hematology: blood samples collected at necropsy were analyzed for the following parameters: hemoglobin concentration, hematocrit value, erythrocyte counts, total and differential leucocyte counts and platelet counts. Red cell indices were calculated. The myeloid/erythoid ratios were determined on bone marrow for the animals of the control group and the group receiving 12.5 mg/kg b.w. mercuy chloride (9.2 mg/kg Hg).

- Biochemistry: The serum was analyzed for sodium, potassium, inorganic phosphorus, total bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), total protein, calcium, cholesterol, glucose, uric acid and lactate dehydrogenase (LDH). A liver sample (2.0 g) was excised and homogenized in tris-buffer (pH 7.4) for the determination of microsomal aminopyrine demethylase (APDM) (Cochin and Axelrod (1959). J. Pharmacol. Exp. Therap., 125, 105.), aniline hydroxylase (AH) (Fouts, J.R. (1963), Ann. N.Y. Acad. Sci., 104, 875.) and ethoxyresorufin deethylase activities (EROD) (Burke and Mayer (1974) Drug. Metab. Dispos. 2, 583 - 589.).

- Atomic absorption spectroscopy: Residues of Hg were determined by atomic absorption spectroscopy (Wren et al. (1980) Bull. Environ. Contam.Toxicol., 25, 100.) in the following tissues: brain, liver, kidney, spleen, serum and fat.
No further information on the study design was stated.

Statistics:

Data were analyzed by one-way analysis of variance followed by Duncan's multiple range test to indicate the groups which were significantly different from the control (p≤ 0.05) (Nie, N.H. et al. (1977). Statistical Programs for the Social Sciences, SPSS, Inc., Chicago.)

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 12.5 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Findings: mild to moderate morphological changes in kidneys, decrease of lactate dehydrogenase activity, increasse in serum cholesterol and phosphorus levels.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 9.2 mg/kg bw

Based on:

element

Remarks on result:

other: This is the LD50 value for the element mercury recalculated from mercury chloride.

Mortality:

No deaths occurred.

Clinical signs:

other: No data

Gross pathology:

Mild to moderate morphological changes were noted in the kidneys of animals treated with mercury chloride. Changes in kidneys consisted of protein casts, cellular casts and interstitial sclerosis.

Other findings:

- Organ weights: weights of the organs were not affected by the treatment with mercury chloride.

- Biochemistry: the lactate dehydrogenase (LDH) activity was significantly decreased in animals of both groups receiving mercury chloride. There was an increasse in the serum cholesterol and phosphorus levels in the animals that were administered the high dose of mercury chloride. Animals that received the low dose mercury chloride showed a significant decrease in the serum protein (control: 6.20 +/- 0.43, 10 mg HgCl2: 5.54 +/- 0.61 g/dl) and calcium (control: 10.7 +/- 0.3, 10 mg HgCl2: 9.7 +/- 0.8 mg/dl). No other biochemical changes were observed, and liver microsomal enzyme activities were not affected.

-Hematology: significant decrease in red blood cell count and hematocrit were seen.

Applicant's summary and conclusion

Interpretation of results:

other: The study was not desigend establish an LD50

Remarks:

Criteria used for interpretation of results: expert judgment

Conclusions:

In conclusion, a broad range of toxicological changes manifested in rats dosed with mercury chloride (10.0 and 12.5 mg/kg b.w. ). Organ weights were not affected, but mild to moderate morphological changes were noted in kidneys. Biochemistry revealed decreased levels of lactate dehydrogenase (LDH) activity in animals of both groups, and there was an increasse in the serum cholesterol and phosphorus levels in high dose animals. Liver microsomal enzyme activities were not affected. Hematology showed significant decreases in red blood cell count and hematocrit.