Lead titanium trioxide

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

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 intr-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 ug/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 ther uteri.

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  : (H360Df)

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