Registration Dossier

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:
Unnamed
Year:
1981

Materials and methods

Objective of study:
distribution
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

Reference
Name:
Unnamed
Type:
Constituent
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

Species:
dog
Strain:
other: Kelpie-cross
Sex:
male/female

Administration / exposure

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

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
Type:
distribution

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

Conclusions:
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.