Tetralead trioxide sulphate

Repeated dose toxicity: dermal

Administrative data

Endpoint:

repeated dose toxicity: dermal, other

Remarks:

The cutaneous penetration of lead oleate, acetate, and arsenate through the skin

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Well-documented and corresponded to the criteria set for assessing animal studies in (Klimisch, et. al. 1996)- A Systematic Approach for Evaluating the Quality of Experimental Toxicological and Ecotoxicological Data, giving due consideration to the published data quality criteria in place at the time the study was conducted.

Data source

Reference

Reference Type:

publication

Title:

The Penetration of Lead Through the Skin

Author:

Laug and Kunze

Year:

1948

Bibliographic source:

The Journal of Industrial Hygiene and Toxicology with Abstracts of the Literature (1948) Vol. 30 pp. 256-259

Materials and methods

Principles of method if other than guideline:

On the basis of the author's experience that urinary excretion might prove too insensitive for demonstration of minute cutaneous penetration, a method recently devised by Laug (1947) in his laboratory for determining cutaneous penetration of mercury was applied to lead.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Lead dioleate

EC Number:

214-310-0

EC Name:

Lead dioleate

Cas Number:

1120-46-3

Molecular formula:

C18H34O2.1/2Pb

Constituent 2

Reference substance name:

Lead ortho arsenate

Cas Number:

3687-81-8

IUPAC Name:

Lead ortho arsenate

Constituent 3

Reference substance name:

Acetic acid, lead salt, basic

EC Number:

257-175-3

EC Name:

Acetic acid, lead salt, basic

Cas Number:

51404-69-4

Constituent 4

Reference substance name:

Tetraethyllead

EC Number:

201-075-4

EC Name:

Tetraethyllead

Cas Number:

78-00-2

Molecular formula:

C8H20Pb

IUPAC Name:

tetraethylplumbane

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: Lead acetate-aqueous solution; lead ortho arsenate-aqueous paste; lead oleaate-ointment-petrolatum and oleic acid; lead tetraethyl-alone.

Details on exposure:

Lead oleate-148 mg
Lead acetate-77 mg 1.5 x 3 inches-clipped dorsal skin
Lead arsenate-102 mg
Lead tetraethyl-106 mg

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Chemical analyses show that the lead concentraion in the kidney within twenty-four hours after skin exposure is significantly greater than incontrols, and may be used as a measure of the amount of lead which has entered the body via this route.

Duration of treatment / exposure:

Twenty-four hours

Frequency of treatment:

Continual treatement on the skin for 24 hours.

Doses / concentrations

Remarks:

Basis: analytical per unit area

No. of animals per sex per dose:

Lead oleate-avg. 12 rats
Lead acetate-avg. 6 rats
Lead arsenate-avg. 8 rats
Lead tetraethyl-nine rats

Control animals:

yes

Details on study design:

Rats were used in this study. They were lightly anesthetized and the lead preparation applied to an area of 29 (cm.) squared (11/2x3inches) of the clipped dorsal skin. Inunction was made for two minutes with a glass rod. Then, without removal of excess, the animal was wrapped in a cylindrical celluloid shield, cemented to the body at shoulders and hips. The shield was sufficiently stiff so that the animal was confinef after the fashion of a straight jacket, and was thus prevented from bending its body or coming in oral contact with the shield. The shield did not, however, limit the rat from walking about its cage, nor did it interfere with its intake of food and water. At the end of twenty-four hours, the animal was killed and exsanguinated and the kidneys removed for chemical analyses of lead. Owing to the fact that measurable quantities of lead are also found in the kidneys of unexposed animals, it was necessary to analyze an equal number of controls with equal exposure series.
Four lead compounds were studied: 1) Lead acetate in aqueous solution (77 mg lead per rat); lead ortho arsenate in aqueous paste (102 mg lead per rat); 3) lead oleate as an ointment petrolatum and oleic acid vehicles (148 mg lead per rat); 4) Lead tetraethyl (106 mg lead per rat). For mechanical reasons, it was not possible to apply equal quantities of lead, but in every case a considerable excess of lead compound remained on the skin. No adjustment of exposure area or of age on a body-weight basis was made, but the animals were of uniform size and ranged in weight from 300 to 350 grams.

Positive control:

Owing to the fact that measurable quantities of lead are also found in the kidneys of unexposed animals, it was necessary to analyze an equal number of controls with equal exposure series.

Examinations

Observations and examinations performed and frequency:

Measure of amount of lead stored in the kidneys. Distribution of lead in tissues for lead oleate exposure and lead tetraethyl exposure.

Sacrifice and pathology:

At the end of 24 hours the animals were kileed and exsanguinated and the kidneys were removed for chemical analyses.

Statistics:

Simple comparisons

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

no mortality observed

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:

effects observed, treatment-related

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

Table 1 shows the comparative penetration of lead from lead acetate, lead orthoarsenate, and lead oleate. Lead arsenate was included because of its frequent use as an insecticide. The penetration from lead arsenate is significantly less than that from either the oleate or the acetate. In fact, in comparison with all of the control values, it would appear that the penetration of lead from the arsenate compound is practically nil. There is indication that the skin is more permeable to lead acetate than lead oleate; however, the difference between these compounds just misses significance at the 5 percent level. It can be seen that in contrast to the other lead compounds studied, large quantities of lead tetraethyl were absorbed through the skin and could be found not only in the kidneys but in all other tissues examined. It is evident form the data presented that from 90 to 95 per cent of the lead tetraethyl applied to the skin must have been lost by evaporation before it could penetrate the skin. Even so, the difference between the permeability of the skin to nonvolatile lead compounds such as lead acetate, arsenate, oleate and lead tetraethyl is most striking. Not only are the kidney values 10 to 20 times higher, but it appears that the entire organism becomes flooded with lead (Table 2).

Effect levels

Dose descriptor:

other: Penetration of lead through intact skin

Effect level:

ca. 106 other: mg of tetraethyl lead

Based on:

other: 0.1ml tetraethyl lead

Basis for effect level:

other: Absorption in comparison to the other lead compounds studied.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1-Comparison of the Cutaneous Penetration of lead From Four Different Compounds

The measure of penetration of lead is the storage of lead in the kidneys of the rat

	micrograms Pb per gram wet kidney
	24-Hour Exposure	Control
Lead Oleate (148 mg. lead per rat) Avg. 12 rats	1.3	0.59
Lead Acetate (77 mg. lead per rat) Avg. 6 rats	1.8	0.82
Lead Arsenate (102 mg. lead per rat) Avg. 8 rats	0.85	0.55
Lead Tetraethyl (106 mg. lead per rat) Avg. 9 rats	136

Table 2-The Total Amount of lead Distributed In The Carass and Tissues of the Rat Following Exposure to 106 mg. lead as Lead Tetraethyl.

Micrograms of Pb in the Whole Tissue	kidney	liver	lung	blood	carcass	exposed skin area
Average	136	505	182	960	4991	1675

Applicant's summary and conclusion

Conclusions:

The authors concluded that (1) cutaneous absorption of lead oleate, lead acetate, and lead arsenate, as measured by the storage of the lead in the kidneys, is extremely small; (2) mechanical injury to the skin iincreases the penetration of lead; and (3) the absorption of lead tetraethyl is much higher, with concentrations of lead in the kidneys being 10-to20-fold higher than the three nonvolatile lead compounds.

Executive summary:

Rats were lightly anesthetized and preparations of lead acetate (77 mg Pb/rat), lead ortho arsenate (102 mg Pb/rat) or lead oleate (148 mg Pb/rat) were applied to an area of 29 square centimeters of clipped dorsal skin. In some experiments, mechanical injury to the skin was induced prior to application. The substances were rubbed in for two minutes with a glass rod, then, without removal of excess, the animals were wrapped in a cylindrical celluloid shield cemented to the body at the shoulders and hips, which prevented bending of the body and oral contact with the shield. After 24 or 48 hours, animals were sacrificed and various organs were removed for measurement of lead. An equal number of control animals were analyzed with each exposure. In the experiments with lead oleate in petrolatum vehicle, the concentration of lead in kidney and in skin from the leg was higher in treated animals compared to controls. The lead concentration was not higher in liver, muscle, lung, brain, spleen, gastrointestinal tract, or thigh bone. Absorption of lead acetate and lead oleate, as measured in the kidney, was higher when applied to skin that underwent mechanical injury. A comparison of the absorption of lead in the kidney from lead oleate, lead acetate, and lead arsenate indicated that absorption of lead arsenate was similar to control values. The absorption of lead acetate appeared to be higher than that of lead oleate, but the difference was not statistically significant. Absorption of lead from these three lead compounds was also compared to that of lead tetraethyl. Measurements of lead in kidneys were 10- to 20-fold higher with lead tetraethyl than with the three nonvolatile lead compounds. The authors concluded that: (1) cutaneous absorption of lead oleate, lead acetate, and lead arsenate, as measured by the storage of lead in the kidneys, is extremely small; (2) mechanical injury to the skin increases the penetration of lead; and (3) the absorption of lead tetraethyl is much higher, with concentrations of lead in the kidneys being 10- to 20-fold higher than the three nonvolatile lead compounds.