Lead titanium zirconium oxide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Dose descriptor:

LOAEL

250 mg/kg bw/day

Species:

rat

Additional information

Administration of lead acetate by drinking water (oral exposure) to males and females rats showed a decrease in body weight, testicular weight, testicular ascorbic acid and seminiferous tubule diameter. The reproductive NOAEL and systemic LOAEL from this study were both 0.25 g/L.

In an another study, after an exposure to 0.5 lead acetate in drinking water from day 1 of intra-uterine life until 60 days after birth, the lead-exposed male and female were compared to unexposed females and males, to examine the effect of lead exposure on reproductive function. Male fertility was not affected but reduced female fertility was observed: litters were smaller and a smaller number of implantation sites was found in lead-exposed females. In lead-exposed males, the weights of the body, testes and epididymes diminished by about 13% and seminal vesicle and ventral prostate weights, by about 29%. Testicular histology and the number and morphology of epididymal spermatozoa were normal.

The hypothesis is that lead has a direct effect on seminal vesicle and ventral prostate weights as well as a secondary effect resulting from possibly reduced food consumption by lead-exposed mice cannot be excluded.

Consequently, in male, exposure to lead might affect reproductive function by acting directly and/or indirectly on accessory sex organs.

Short description of key information:

The authors concluded that lead may inhibit spermatogenesis at the pre-meiotic stage via lack of testosterone production from Leydig cells. In addition, lead exposure in utero and during the first 60 days of post-natal life leading to a blood lead level above the upper limit of 70 µg/dl proposed by the European union for occupational exposure, did not significantly impair male fertility. Female fertility was impaired by the reductions in litter size and the number of implants in their uteri.

Effects on developmental toxicity

Description of key information

The existing data indicate that lead exposure will not lead to increased frequency of congenital abnormalities in humans. Data relating prenatal blood levels to preterm delivery, gestational age and/or birth weight are mixed and provide uncertain results. Weight of evidence evaluation indicates that effects do not occur at blood lead levels up to 30 µg/dL, but are not adequate to determine the extent of the higher exposure levels that would be required to produce effects. A NOAEL of 30 µg/dL is recommended for pregnancy outcome on a precautionary basis.

Additional information

Effects of prenatal lead exposure upon neurobehavioural performance measures have been demonstrated in studies of experimental animals and presumably will occur in humans. However, available data are inadequate to establish the dose-effect relationships that characterize this endpoint. While effects have been observed upon early measures of mental and physical development, attenuation of effects typically occurs over time and, in most studies, are not associated with impacts upon measures such as IQ. However, effects of prenatal lead exposure upon IQ can be difficult to dissociate from those of postnatal exposure. An effect of pre-natal lead exposure has been suggested by two of nine longitudinal studies and has only been reported to persist in one. Effects observed are secondary in magnitude to those produced by exposures after birth, but blood lead levels above 10 µg/dL have been suggested to exert an effect. Although the effects under consideration would not constitute material impairment of an individual child born to a woman with a blood lead level in the range of 10 – 20 µg/dL, maintenance of the blood lead levels of pregnant women at or below 10µg/dL is advised. In essence this is designating 10 µg/dL as the NOAEL for prenatal effects of lead exposure upon neurobehavioural development in children.

Justification for classification or non-classification

Lead compounds not otherwise specified in Annex 1 of Directive 67/548/EEC are classified as follows:

 Repr. Cat. 1; R61 (may cause harm to the unborn child)

 Repr. Cat. 3; R62 (possible risk of impaired fertility)

Under the CLP this classification is designated as:

Repro. 1A  : (H360FD)

Classification for reproductive toxicity is supported by the experimental data and observational human studies. Evidence of impact upon human male fertility indicates consideration of Repr. Cat. 3 being changed to Repr. Cat. 1