[phthalato(2-)]dioxotrilead

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1978

Materials and methods

Objective of study:

other: absorption and excretion

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Four infant (2 male/2 female) and four adult (female) rhesus monkeys were administered a single dose of 10 mg (5 uCi) per kg body weight 210-lead acetate by gavage. Urine and feces were collected at 24-hour intervals for 23 days and the amount of lead in each sample was measured using a gamma scintillation counter. Blood was drawn daily from the femoral vein and blood lead concentrations were determined using a modified Delves cup technique and an atomic absorption spectrophotometer.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Lead acetate

EC Number:

239-379-4

EC Name:

Lead acetate

Cas Number:

15347-57-6

IUPAC Name:

lead(4+) tetraacetate

Details on test material:

Radiolead acetate was prepared by mixing 400 mg lead acetate and 1.7 ug 210Pb nitrate in distilled water to make 100 mL, then allowing the solution to equilibrate overnight.

Radiolabelling:

yes

Remarks:

[210] lead acetate

Test animals

Species:

monkey

Strain:

other: Mucaca mulatta

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 5 to 7 months (infants); 7 to 10 years (adults)
- Weight at study initiation: 1.03 to 1.35 kg (infants); 5.35 to 7.8 kg (adults)
- Housing: Stainless steel metabolism cages equipped with urine and fecal collection trays
- Diet: Purina chow, ad libitum
- Water: Ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Duration and frequency of treatment / exposure:

Single administration of test material.

Doses / concentrations

Remarks:

Doses / Concentrations:
10 mg (5 uCi) per kg body weight.

Control animals:

no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Infant monkeys absorbed 37.9% of the administered dose of 210-lead acetate whereas adults absorbed 26.4% (p < 0.1). The absorbed dose for each animal was calculated as the administered dose minus fecal elimination for 96 hours post-exposure.

Details on distribution in tissues:

The retention of 210-lead and body burden as mg 210-lead per kg body weight was calculated after 23 days. Infants carried a higher body burden (3.57 mg/kg) than adults (2.18 mg/kg), likely due to increased absorption and decreased fecal excretion of absorbed lead in infants.

The blood lead concentrations increased to a higher level, decreased at a slower rate, and remained higher in infants than in adults. Linear regression analysis indicated an inverse correlation between peak and average blood lead values with body burden and percent absorption (peak blood lead vs. body burden, r = -0.872; peak blood lead vs. percent absorption, r = -0.787; average blood lead vs. body burden, r = -0.826 ; average blood lead vs. percent absorption, r = -0.713). These data indicate that 210-lead may have a greater affinity for tissue than for blood components in infants compared to adults.

Details on excretion:

Peak lead elimination via feces was observed in about 24 hours in both age groups. Clearance of lead from the gastrointestinal (GI) tract was shorter in the infants than in the adults, likely due to the shorter length of the juvenile intestine and the shorter resident time of the intestinal contents.

Infant monkeys excreted less of the absorbed lead into urine (3.84%) compared to adults (5.31%), but the difference was not statistically significant. Fecal excretion of absorbed lead by infants (3.45%) was less than that by adults (13.0%). By 23 days post-exposure, infants excreted a total of 7.29% of the absorbed dose of lead compared to 18.3% total excretion by adults.

Applicant's summary and conclusion

Conclusions:

The authors concluded that increased absorption of administered lead and reduced fecal excretion of absorbed lead in infant monkeys resulted in greater body burden of lead compared to adult monkeys.

Executive summary:

Experiments were conducted to measure the GI absorption and elimination of a single oral dose of lead-210 acetate in infant and adult rhesus monkeys. Urinary and fecal excretion of absorbed lead were examined for 23 days post-exposure. Infant monkeys eliminated less and absorbed more of the administered lead. Adult animals excreted more absorbed lead in feces, whereas urinary excretion was similar between adults and infants. Increased absorption of administered lead and reduced fecal excretion of absorbed lead resulted in a greater body burden of lead in infant animals compared to adults. Blood lead concentrations were inversely correlated with body burden and percent absorption of ingested lead.