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Administrative data

Description of key information

Lead has been documented in observational human studies to produce toxicity in multiple organ systems and body function including the haemotopoetic sytem, kidney function, reproductive function and the central nervous system.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
LOAEL
0.005 mg/kg bw/day
Study duration:
chronic
Species:
rat

Mode of Action Analysis / Human Relevance Framework

Additional information

Documentation of repeated dose toxicity from lead exposure is extensive and includes detailed evaluations of effects in humans. Research in animals serves to support causality in epidemiology studies and/or the elucidation of mechanisms of toxicity. The dose response for health effects in human can usually be defined with precision and indexed to internal measures of systemic exposure such as the concentration of lead in blood. Effects assessment indexed to external dose is thus not necessary.

In many instances the toxic manifestations of lead are mediated by interaction of the lead ion with cellular proteins (e.g. metalloenzymes) in place of essential trace minerals such as calcium, zinc or iron. As such, the initial effects of lead upon the function of specific metabolic, cellular, or organ system processes will be detectable as increases or decreases in the activity of specific metalloenzymes. The biological and clinical significance of such interactions requires careful assessment of the extent of enzyme activity alteration and whether or not the alteration alters metabolic pathways to an extent that is of health significance.

The toxic effects of lead (by oral route) were observed when administered to rats in doses of 0.05 mg/kg (substantial increases in the weight coefficients of liver and kidneys...) with a short term exposure 20 -30 days . The activity of aldolase increased and the level of sulfhydryl groups decreased 5-10 days after intoxication (0<0.01). The effect of the 0.005 mg/kg bw/day dose (LOEL) was expressed as a trend in the increase of aldolase in the blood serum. By the 20th day of intoxication the activity of aldolase normalized., and the activity of other enzymes (B-galactosidase, B-glucosidase...) and cholesterol content of the blood serum did not change. In animals which were exposed to 0.0015 mg/kg of lead (NOEL), no deviation in functional state was observed compared to the control group of animals.

For long term exposure -6 to 12 months- histological and histochemical studies of gonads, liver and kidney showed disruptions in the funcional and morphological conditions at doses of lead of 0.05 and 0.05 mg/kg bw/day. The 0.0015 mg/kg dose of lead (which corresponds to 0.03 mg lead/l. water) did not cause any changes. It can be considered that this dose does not have an effect on the organism.

Studies on newborn mice exposed for 28 days at 2.5 mg/m3 of aerosolized Pb(NO3)2 revealed that aerosolized lead is more immunosuppressive than equivalent amounts of ingested lead. This is most likely due to the greater absorption of inhaled lead and the subsequent cytotoxicity of lead for cells in the draining lymph nodes.


Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: other

Justification for classification or non-classification

Demonstration of toxicty in humans is the basis for a recommended classification of STOT RE1. Current classification is STOT RE2.