Mercury

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Inadequate experimental methodologgy and an absence of study details prevent a determination of the amount of mercury.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Experimental studies of the mode of absorption of mercury when applied by inunction

Author:

Schamberg, J.F. et al

Year:

1918

Bibliographic source:

JAMA, 70, 142

Materials and methods

Principles of method if other than guideline:

5 rabbits received dermal treatment with mercury by rubbing in an ointment consiting of 50 % elemental mercury or 50 % mercury chloride for 5 minutes. From 0.5 to 1 g/kg mercury was applied to the skin. Animals received beween 2 and 4 rubbing within 5-12 days.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Mercury ointment

IUPAC Name:

Mercury ointment

Details on test material:

An ointment, consistend in nearly all of the experiments of a 50 % elemental mercury ointment or of a 50 % mercury chloride ointment, was used during the experiment.
No further information on the test material was stated.

Test animals

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

- Weight at study initiation: 1400 gm to 2420 gm
No further information on the test animals was stated.

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

A specific box to house one rabbit was constructed in order to prevent exposure by other routes than the dermal. The rabbit which received inunctions of the ointment was placed in the box with its head projecting into the outer air through an aperture in a heavy piece of canvas attached to one end of the box. A padded collar served the double purpose of making the animal comfortable and of preventing the rabbit from breathing the box air.

The hair over considerable area on the back was removed by means of a barium sulphid depilatory in order to avoid as much as possible traumatism that might result from shaving.

The experiment was conducted with 5 rabbits. The amount of ointment employed at each rubbing was very large in order to abbreviate the period of the experiment and to accentuate the findings. From 0.5 to 1 gm of mercury per kilogram was applied to the skin. The ointment was rubbed into the back for five minutes. Considerable unabsorbed ointment remained on the surface of the skin.
The following exposure conditions were used for the rabbits:
Rabbit No. 1: three rubbings within nine days (received elemental mercury)
Rabbit No. 2: two rubbings within five days (received mercury chloride)
Rabbit No. 3: three rubbings within six days (received elemental mercury)
Rabbit No. 4: two rubbings within five days ((received mercury chloride)
Rabbit No. 5: four rubbings within twelve days (received mercury chloride)
No further information on the dermal exposure was stated.

Duration of exposure:

no data

Doses:

Please refer to "Details on dermal exposure".

No. of animals per sex per dose:

Please refer to "Details on dermal exposure".

Control animals:

not specified

Details on study design:

Observation on mortality was made. The diagnosis of mercurial poisoning was based on chemical examination of the organs and histological studies of a number of organs, particularly the kidneys.
No further information on the study design was stated.

Statistics:

no data

Results and discussion

Effect levels

Effect level:

0.5 - 1 other: g/kg

Remarks on result:

other: The five exposed rabbits sucumbed after a brief period to mercurial poisoning. All animals died within 3 to 6 days after the last treatment.

Mortality:

In each of the five experiments, all animals died within 3 to 6 days after the last treatment.
Rabbit No. 1: died four days later
Rabbit No. 2: died five days later
Rabbit No. 3: died three days later
Rabbit No. 4: died three days later
Rabbit No. 5: died six days later

Clinical signs:

other: Rabbits sucumbed after a brief period to mercurial poisoning.

Gross pathology:

Please see "Other findings" below

Other findings:

- Histopathology/pathology:
Rabbit No. 1: acute hyperemia of the glomeruli and intertubular tissues of the kidneys, also slight cloudy swelling, but no calcification. The lungs exhibited no pathological changes, and the liver was likewise normal.
Rabbit No. 2: kidneys revealed acute hyperemia, but no other changes. The lungs, heart, spleen and suprarenal glands were normal.
Rabbit No. 3: kidneys revealed cloudy swelling of the epithelium of the tubules, with oedematous distention of the malpighian tufts, marked oedematous distention of the tubules, but no calcification. the lungs were normal.
Rabbit No. 4: kidneys disclosed acute hyperamia of the glomeruli and slight cloudy swelling with acute congestion.
Rabbit No. 5: oedema of the tufts of the kidneys, with slight exudative glomerulitis and cloudy swelling of the tubules was observed. There were no changes in the lungs.

- Chemical examination:
Rabbit No.1: no chemical examination of the organs of this rabbit was made.
RAbbit No. 3: large amounts of mercury were found in the kidneys, liver and skin; the lungs was free of mercury, but faint trace was present in the brain. This animal was pregnant, and the placenta and fetus were found negative to tests for mercury.
Rabbit No. 4: kidneys, liver and skin were found to contain relatively large amounts of mercury, and there was a small quantity in the lung.
Rabbit No. 5: relatively large quantities of mercury were detected in the kidneys, liver and skin, but ite was absent in the lungs.

Any other information on results incl. tables

The five exposed rabbits sucumbed after a brief period to mercurial poisoning. All animals died within 3 to 6 days after the last treatment.

Applicant's summary and conclusion

Conclusions:

Five rabbits treated dermally with high dose levels of mercury containig ointments succumbed after a brief period of mercurial exposure. All animals died within 3 to 6 days after the last treatment. Histopathology revealed morphological changes in kidneys.