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Toxicological information

Toxicity to reproduction

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Administrative data

fertility, other
based on test type (migrated information)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles.

Data source

Reference Type:

Materials and methods

Test guideline
no guideline followed
Principles of method if other than guideline:
Male Sprague-Dawley rats were administered lead-free or 0.3% lead-containing water for 14, 30, or 60 days and sperm parameters were measured.
GLP compliance:
Limit test:

Test material

Constituent 1
Reference substance name:
Lead acetate
EC Number:
EC Name:
Lead acetate
Cas Number:
lead(4+) tetraacetate
Details on test material:
Lead acetate was purchased from Fisher Scientific (Springfield, New Jersey).

Test animals

Details on test animals or test system and environmental conditions:
- Age at study initiation: 100 days
- Housing: Animals were housed in plastic cages.
- Diet: Ad libitum; laboratory chow.
- Water: Ad libitum; distilled, deionized water
- Acclimation period: 7 days.

- Photoperiod: 12 hours dark/12 hours light

Administration / exposure

Route of administration:
oral: drinking water
Details on exposure:
Control animals were given ad libitum access to deionized, distilled water containing no lead acetate. Lead-treated animals received a 0.3% lead acetate solution.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Animals were treated for 14, 30, or 60 days.
Frequency of treatment:
Animals drank lead acetate-containing water ad libitum.
Doses / concentrations
Doses / Concentrations:
0.3 % lead acetate solution
nominal in water
No. of animals per sex per dose:
Control animals:
yes, concurrent no treatment
Details on study design:
In a separate study, nine adult male rats were given ad libitum access to deionized, distilled water, and 10 male rats were given access to a 0.3% lead acetate solution. After 60 days, animals were terminated and testes were harvested for DNA flow cytometry.
Positive control:


Parental animals: Observations and examinations:
Animals were weighed weekly.
Sperm parameters (parental animals):
Parameters included epididymal sperm concentration, ability of sperm to fertilize ova in vitro, ultrastructural organization of spermatozoa, and measurement of spermatogenesis by DNA flow cytometry.
Postmortem examinations (parental animals):
After the 14, 30, or 60-day treatment period, animals were decapitated and blood was collected for lead analysis. The caudae epididymi were removed and weighed. Epididymal sperm counts were performed and an epidymal sperm suspension was prepared for insemination. Sperm were incubated with ova harvested from non-lead-exposed female rats and penetration was assessed. Epididymal sperm were also prepared for morphological assessment by transmission electron microscopy.
The data for each stage of penetration/fertilization are expressed as the percentage of total incubated ova for each animal. Multivariate analysis of variance was used to compare the distribution of penetration/fertilization stages between groups. Blood lead measurements, body and tissue weights, and sperm counts were compared using one-way univariate ANOVA. DNA histogram cell counts were compared using Student's t-test.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not examined
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
effects observed, treatment-related
Reproductive performance:
effects observed, treatment-related

Details on results (P0)

BODY AND ORGAN WEIGHTS: Lead acetate did not affect body weight or weight of the right caudia epididymis.

BLOOD LEAD LEVELS: Blood lead levels were statistically significantly higher in all of the lead-treated groups compared to the control group.

REPRODUCTIVE FUNCTION: SPERM MEASURES: Epididymal sperm concentrations were statistically significantly decreased in rats treated with lead for 14, 30, and 60 days. There were no differences among groups of testes cell types (haploid, diploid and tetraploid) from control animals and lead-treated animals as determined by DNA flow cytometry.

REPRODUCTIVE PERFORMANCE: Sperm harvested from animals treated for 14, 30, and 60 days penetrated statistically significantly fewer eggs compared to controls; however, increased duration of exposure to lead acetate from 14 to 60 days did not result in a higher percentage of unfertilized eggs.

HISTOPATHOLOGY: No ultrastructural changes were noted in the spermatozoa of animals treated with lead compared to controls.

Effect levels (P0)

Dose descriptor:
Effect level:
0.3 other: %
Basis for effect level:
other: Based on decreased epididymal sperm concentrations and decreased penetration of eggs at 0.3% lead acetate in water.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

The authors concluded that lead alters sperm function by altering the hormonal control of spermatogenesis rather than by direct disruption of the sperm cells.
Executive summary:

Male Sprague-Dawley rats were administered lead-free or 0.3% lead-containing water for 14, 30, or 60 days and sperm parameters were measured. Lead disrupted the ability of sperm harvested from lead-exposed animals to penetrate or fertilize eggs harvested from non-exposed females in vitro. Lead also decreased epididymal sperm count. Lead did not affect the weight of the right cauda epididymi and it did not induce any ultrastructural changes in spermatazoa or any DNA histogram abnormalities in testicular cells. The authors stated that these observations suggest that the impaired ability of lead-exposed sperm to penetrate and fertilize eggs in vitro may be attributed to the difference in circulating hormone levels rather than to a direct toxic action of lead on spermatozoa.