Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
The Deposition and Removal of Lead in the Soft Tissues (Liver, Kidneys, and Spleen)
Author:
Fairhall LT & Miller JW
Year:
1941
Bibliographic source:
Public Health Reports Vol. 56 No. 33 (Reprint No. 2304), pages 1641-1650

Materials and methods

Objective of study:
distribution
Principles of method if other than guideline:
Frequently the metal content of a given tissue is related to its pathology and because of the probable variable shift in amount of the deposited material within a relatively short time the following experiments were undertaken to verify this and to find out the extent to which this shift occurred with lead during a reasonable interval. As a change in the soft tissue content of lead had been noted in similar groups of animals killed within less than a week after lead ingestion had ceased, it was felt that a 14-day rest period would be sufficient to indicate a definite difference.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Lead carbonate
EC Number:
209-943-4
EC Name:
Lead carbonate
Cas Number:
598-63-0
Molecular formula:
CH2O3.Pb
IUPAC Name:
λ²-lead(2+) carbonate
Radiolabelling:
not specified

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Duration and frequency of treatment / exposure:
66 (52 +14) days
Doses / concentrations
Remarks:
Doses / Concentrations:
15 mg / day during 52 days
Control animals:
not specified

Results and discussion

Main ADME results
Type:
distribution

Toxicokinetic / pharmacokinetic studies

Details on absorption:
When lead is absorbed into the body there occurs a general flooding of all the tissues by the lead stream, which the system as a whole tends to correct either by increased excretion or by deposition of the lead in the bone tissue.
Details on distribution in tissues:
The average content in the livers of the former group was 0.020 mg. per liver, or a concentration of 0.032 mg. per 10 gm. of tissue.
The average content in the livers of the group following the rest period was 0.011 mg., or 0.016 mg. per 10 gm. of liver.
Similarly, the average content in the kidneys of the first group was 0.055 mg., or 0.427 mg. per 10 gm. of kidney, while in t.he second group the average lead content was 0.031 mg. per kidney, or 0.217 mg. per 10 gm. of tissue.
The average lead content in the spleens of the first group was 0.003 mg., as compared with 0.004 mg. in the second group, but, as stated previously, these quantities are so low that comparisons are scarcely reliable.
In contrast, with the lead content of the softer tissues, the bones show a slight increase in lead content in the second group, although these imals received no more lead than the first group and furthermore had an opportunity of excreting part of the lead during the 14-day rest period.
The average amount of lead present in the bones of the animals of the first group was 0.93 mg. per animal, or 3.30 mg. per 10 gm. of bone tissue, while that of the second group was 1.14 mg. per animal, or 3.65 mg. per 10 gm. of bone tissue.

Metabolite characterisation studies

Metabolites identified:
not specified

Any other information on results incl. tables

It has been shown that lead deposited in the softer tissues in rats fed approximately 15 mg. of lead carbonate a day for 6 weeks is transitory in nature and may be diminished by 50 percent within 2 weeks merely by restoration to a normal diet. Coincidently there is a slight rise in the lead content of the bone tissue.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
In the conditions of the study, lead carbonate did not show a high bioaccumulation in rats.