Lead Carbonate Intermediate

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

supporting study

Materials and methods

Type of study / information:

Bioavailability of ingested lead in humans.

Endpoint addressed:

basic toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

This study examined the bioavailability of lead in wine using a human in vivo model. The study was a single-dose, nonrandomized cross-over study. Blood was obtained for screening of lead isotope ratios from 61 adult subjects in New York, United States; 10 adult subjects in Glasgow, Scotland; and 12 adult subjects in Brisbane, Australia. In New York, six subjects were chosen (ages 21-40 years), with blood lead concentrations <0.24 µmol/L, and 206Pb/207Pb ratios ≥1.195. Participants were admitted to the Clinical Research Center twice, one week apart. During the first admission, subjects ingested sherry obtained from the original bottle. During the second admission, they ingested sherry that had been stored for three years in a lead-crystal decanter and had a lead concentration of 14.2 µmol/l. The ratio of 206Pb/207Pb and total lead content were simultaneously measured in the blood and the urine.

GLP compliance:

no

Method

Ethical approval:

confirmed and informed consent free of coercion received

Details on study design:

SETTING: Clinical Research Center
HEALTH EFFECTS STUDIED: In vivo bioavailability of lead.

Results and discussion

Results:

Most New York subjects had blood 206Pb/207Pb ratios of 1.195 or higher. Australian subjects had the lowest 206Pb/207Pb ratios, ranging from 1.095 to 1.145. Scottish subjects had only slightly higher values, ranging from 1.105 to 1.155. Table 1 presents the results of this study. Prior to the ingestion of sherry that had been in a lead-crystal decanter (206Pb/207Pb = 1.078), the mean blood lead level was 0.10 µmol/L and the mean 206Pb/207Pb ratio was 1.202. After consumption of the sherry, the blood lead levels rose and the 206Pb/207Pb ratio fell to attain values in the range 1.118-1.150 at 48 hours. These changes were essentially complete by 24 hours, at which time the mean blood lead level had risen to 0.18 µmol/L (p = 0.0003) and the mean blood 206Pb/207Pb ratio had fallen to 1.137 (p = 0.0001). In contrast, neither blood lead level (Table 1), blood 206Pb/207Pb ratio, nor ALAD changed significantly after the consumption of sherry obtained from the original bottle. On average, by 24 hours, 38.4% of the administered lead dose was in the blood compartment. Bioavailability was estimated by comparing the kinetics of an oral dose to those of an intravenous dose. Previous studies of intravenous 203Pb indicate that at 24 hourw, 55% of an administered dose is still in the blood compartment. The authors estimated the mean fraction of lead absorbed from the sherry to be 70%. Individual values for bioavailability were 96, 83, 77, 71, 47, and 46%.

Any other information on results incl. tables

Table 1: Demographics and findings of the study.

					Control Hospitalization		Lead Crystal Hospitalization
					BPb (µmol/L)			BPb (µmol/L)		206Pb/207Pb
Subject	Age (years)	Weight (kg)	Race	Gender	Start	24 hr	Dose Pb (µmol)	Start	24 hr	Start	24 hr	% Absorbed
1	24	60.6	White	F	0.16	0.16	1.04	0.17	0.29	1.206	1.148	96
2	23	58.2	Black	F	0.09	0.07	1	0.06	0.16	1.202	1.12	83
3	28	48	Asian	F	0.06	0.07	0.83	0.07	0.14	1.204	1.144	46
4	26	73.5	White	M	0.1	0.1	1.26	0.1	0.19	1.199	1.135	77
5	24	80	Black	M	0.11	0.11	1.38	0.08	0.14	1.196	1.142	47
6	24	60	Black	F	0.09	0.11	1.03	0.09	0.17	1.202	1.135	71
Mean	25	63.4			0.1	0.1	1.09	0.1	0.18*	1.202	1.137**	70
*p= 0.0003, compared to starting BPb.
**p= 0.0001, compared to starting 206Pb/203Pb ratio.
BPb = Blood lead concentration

Applicant's summary and conclusion

Conclusions:

The authors concluded that lead leached from lead-crystal glass is highly bioavailable as, on average, 70% of the ingested dose of lead was absorbed. Repeated ingestions may cause elevated blood lead concentration. The authors concluded that for a 70-kg subject, a single dose of 0.48 µmol of lead in sherry will induce a rise in blood lead concentration of approximately 0.05 µmol/L. The technique of stable isotope dilution is useful for the study of the bioavailability of lead in other matrices, including soil.

Executive summary:

The authors sought to determine the bioavailability of lead leached from a lead-crystal decanter, using the technique of stable isotope dilution in blood. The bioavailability of lead in any matrix can be determined by isotope dilution provided the isotopic ratio of the ingested samples is sufficiently different from that in the blood of the subjects who ingest it. The lead-crystal decanter was manufactured with lead from Australia, where the ratio of 206Pb/207Pb is distinctly different from that in the United States. The authors conducted a single-dose, nonrandomized cross-over study in which participants were admitted to the Clinical Research Center twice, one week apart. During the first admission, subjects ingested sherry obtained from the original bottle. During the second admission, they ingested sherry that had been stored in the lead-crystal decanter and that had achieved a lead concentration of 14.2 µmol/L. After ingesting decanter-stored sherry, mean blood lead increased (p = 0.0003) from 0.10 to 0.18 µmol/L, while mean 206Pb/207Pb fell from 1.202 to 1.137 (p = 0.0001). On average, 70% of the ingested dose of lead was absorbed. The authors concluded that lead derived from crystal glass is highly bioavailable; repeated ingestions could cause elevated blood lead concentrations. The advantage of the technique of stable isotope dilution is its sensitivity and precision, which allows one to estimate bioavailability even when the fraction of lead absorbed is as low as 5%.