Lead 2,4,6-trinitro-m-phenylene dioxide

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1948

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

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 on 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.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Lead acetate

EC Number:

239-379-4

EC Name:

Lead acetate

Cas Number:

15347-57-6

IUPAC Name:

lead(4+) tetraacetate

Constituent 2

Reference substance name:

Lead ortho arsenate

IUPAC Name:

Lead ortho arsenate

Constituent 3

Reference substance name:

Lead oleate

EC Number:

239-378-9

EC Name:

Lead oleate

Cas Number:

15347-55-4

IUPAC Name:

lead(4+) tetraoctadec-9-enoate

Constituent 4

Reference substance name:

Lead tetraethyl

IUPAC Name:

Lead tetraethyl

Details on test material:

Lead acetate was in aqueous solution, lead ortho arsenate was an aqueous paste, and lead oleate was an ointment in petrolatum and oleic acid vehicles.

Radiolabelling:

no

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No details provided on test animals and environmental conditions, with the exception that the rats were of uniform size and weighed between 300 and 350 grams.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: water; petrolatum; oleic acid

Duration of exposure:

24 or 48 hours.

Doses:

Lead acetate: 77 mg lead/rat
Lead ortho arsenate: 102 mg lead/rat
Lead oleate: 148 mg lead/rat

Control animals:

yes

Remarks:

Negative controls were used, but no information was provided on whether the control animals received vehicle or no treatment.

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Absorption in different matrices:

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 (Table 1). A comparison of the absorption of lead in the kidney from lead oleate, lead acetate, and lead arsenate is shown in Table 2. 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.

Any other information on results incl. tables

Table 1: Effect of injury to the skin on absorption of lead compounds, as measured by lead concentration in kidney (ug lead per gram wet kidney).

	Lead Oleate - Intact	Lead Oleate - Injured	Lead Acetate - Intact	Lead Acetate - Injured
	1.3	4.9	---	---
	3.3	5.1	---	---
	0.80	3.1	1.4	2.3
	0.60	7.1	1.7	4.5
	0.90	4.1	2.9	7.8
	0.82	1.9	1.5	7.2
	1.3	3.8	2.1	6.4
	0.90	3.6	1.0	7.3
Average	1.3	4.2	1.8	5.9

Table 2: Comparison of the cutaneous penetration of lead from three different compounds, as measured by lead concentration in kidney (ug lead per gram wet kidney).

	24 -Hr Exposure	Control
Lead Oleate (n = 12)	1.3	0.59
Lead Acetate (n = 6)	1.8	0.82
Lead Arsenate (n = 8)	0.85	0.55

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 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.

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.