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Administrative data

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

Data source

Reference Type:

Materials and methods

Objective of study:
Principles of method if other than guideline:
Eigth-month-old dogs maintained on a high-fat-low-calcium diet were administred a mixture of lead chloride, lead bromide and lead sulphate for a prolonged periods at 4 different dose levels. Radiological investigations were made.
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
Automatically generated during migration to IUCLID 6, no data available
Automatically generated during migration to IUCLID 6, no data available
Details on test material:
The lead salt mixture consisited of lead chloride, lead bromide and lead sulphate in the proportions 1:1:2 respectively. These lead compounds in approximately similar proportions are the major by-products in the exhaust emission of internal combustion engines which utilize leaded petrol (bloom, 1979, pers. comm.). All dogs were weighed once a week and the dose of lead salt mixture was calculated.

Test animals

other: Kelpie-cross

Administration / exposure

Route of administration:
oral: capsule
other: gelatin
Duration and frequency of treatment / exposure:
From 14 to 155 days
Doses / concentrations
Doses / Concentrations:
0, 5, 15, 30 and 60 mg/kg (bw)
No. of animals per sex per dose / concentration:
0, 5,15, 30 mg/kg (bw) : 2 dogs
60 mg/kg (bw) : 3 dogs
Control animals:

Results and discussion

Preliminary studies:
All the dogs on lead treatment began losing weight a very short time of the commencement of the experiment. The dogs on the lowest dose maintained their weight at the pretreatment levels for one week but then gradually lost weight.
Main ADME results

Toxicokinetic / pharmacokinetic studies

Details on absorption:
In the higher dose groups 3 and 5, blood lead increased to over 200µg/dl within 3 days. The levels then dropped markedly for the next 2 weeks and then gradually increased again. In group 4 (controls), the blood level increased slightly and remained above 35µg/dl in dog H182 for approximately 9 weeks.
Details on distribution in tissues:
Tissues from the dogs administered lead showed higher levels of lead than did the tissues of the control dogs. Generally the highest lead levels were seen in the distal radius, followed by the lumbar vertebra, the bones of the calvarium, liver and kidney, cerebrum and spinal cord.

Applicant's summary and conclusion

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
In the present experiment, it is probable that a high proportion of the administred lead was absorbed from the intestines and this may have contributed to negative radiological findings in a large porportion of the abdominal radiographs.