Registration Dossier

Administrative data

Endpoint:
neurotoxicity: chronic oral
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:
1984

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Eight-month-old dogs maintained on a high-fat-low-calcium diet were administred a mixture of lead chloride, lead bromide and lead sulphte for prolonged periods at 4 different dose levels. The distribution of the neurological lesions of experimental lead toxicity in dogs was recorded and the associated light and electron microscopic changes were described.
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 of treatment / exposure:
From 14 days to 152 days
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 mg/kg (bw)
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
5 mg/kg (bw)
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
15 mg/kg (bw)
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
30 mg/kg (bw)
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
60 mg/kg (bw)
Basis:
nominal conc.
No. of animals per sex per dose:
The dogs were divided into 5 groups of 2 dogs except group 5 (60mg/kg bw) which had 3 dogs.
Control animals:
yes

Results and discussion

Effect levels

Dose descriptor:
conc. level:
Basis for effect level:
other: neuropathology :
Remarks on result:
not measured/tested
Remarks:
Effect level not specified

Any other information on results incl. tables

Dogs H176 and H179 first developped nervous signs on days 24 and 57 respectively, and died on days 50 and 72. Both dogs had convulsive episodes but in H179, the signs were milder than in dog H176.

The lead content of the frontal lobe of the cerebrum was high in dogs with brain lesions. Dog H180 on 30mg/kg/day of the lead salt mixture also had a high brain lead burden but neuropathological changes were not evident on examination by light microscopy.

Neither experimental nor control dogs showed macroscopic neuropathological changes. 7 of the 9 dogs in the experiment had brain lesions which were apparent under light microscope.

Applicant's summary and conclusion

Conclusions:
The brain lead content is not a reliable indicator of lead intoxication in dogs. Furthermore, the severity and the extent of histologically detectable brain lesions did not bear a consitent relationship to the clinical manifestations of lead neuropathy.