Registration Dossier

Toxicological information

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Key value for chemical safety assessment

Effects on fertility

Additional information

In the voluntary Risk Assessment Report for lead and inorganic lead compounds, all available studies in humans and experimental animals have been evaluated for the observed effect of lead upon sexual maturation and semen quality, pregnancy outcome, and neurobehavioural effects of prenatal and postnatal lead exposure. Lead compounds were found to have effects on male fertility, female reproductive parameters, and on neurobehavioural development, which was the most critical effect.

Effects on developmental toxicity

Description of key information
Developmental neurotoxicity of lead and lead compounds: BMDL01 for deficit of 1 IQ point is 1.2 ug/dL blood lead level, or 0.5 ug/kg bw/day
Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
BMDL05
0.5 µg/kg bw/day
Additional information

In the voluntary Risk Assessment Report for lead and inorganic lead compounds, all available studies in humans and experimental animals have been evaluated for the observed effect of lead upon sexual maturation and semen quality, pregnancy outcome, and neurobehavioural effects of prenatal and postnatal lead exposure. Lead compounds were found to have effects on male fertility, female reproductive parameters, and on neurobehavioural development, which was the most critical effect.

 

Effects on neurobehavioural performance after pre-natal and post-natal have been reported in several animal studies. However, the available data are inadequate to establish dose-effect relationships. Observed effects are upon early measures of mental and physical development, but could not be associated with impacts upon measures such as IQ. Furthermore, effects of prenatal lead exposure can be difficult to dissociate from those of postnatal exposure. Effects of pre-natal lead exposure are secondary in magnitude to those produced by exposures after birth. The vRAR suggest a blood lead level above 10 µg/dL (in females) to take into account for the risk assessment with regard to developmental effects.

In the opinion of the Scientific Committee on Health and Environmental Risks (SCHER) on the voluntary Risk Assessment Report (vRAR), it is concluded that the health part of the vRAR is of good quality, comprehensive, and that the exposure and effects assessment follow the Technical Guidance Document.

In the risk assessment on lead from food which was performed by the European Food Safety Authority (EFSA, 2010), the Bench Mark Dose approach (BMD) is used to estimate the BMDL01, which is the blood-lead concentration corresponding to the lower limit 95-percentile of the Confidence Interval of the chosen Bench Mark Response of an IQ deficit of 1 IQ point. The BMR is chosen and set at 1 IQ point by the CONTAM panel of EFSA. Using this approach, the BMDL01 for lead was estimated to be 1.2μg/dL (mentioned as 12μg/L by EFSA).

A supporting study is included in the dossier in which adverse changes were observed when female Swiss albino mice were treated with potassium dichromate at 0, 53.2, 101.1, and 152.4 mg of eq. chromium(VI)/kg/day in drinking at days 6–14 of gestation (Junaid et al., 1996).

The number of dead fetuses (higher in the high-dose group), fetal weight (lower in both intermediate- and high-dose groups; high dose = 1.06 g, intermediate dose = 1.14 g) were changed as compared to the control value of 1.3 g. A dose-response relationship was also observed in the number of resorption sites (0.31 for controls, 1.00 for the low dose, 1.70 for the intermediate dose, and 2.30 for the high dose), as well as a significantly greater incidence of post-implantation loss (in the two highest-dose groups of 21 and 34.60% as compared to control value of 4.32%).

The gross structural abnormalities observed were drooping of the wrist (carpal flexure) and subdermal hemorrhagic patches on the thoracic and abdominal regions (in 16% in the offspring of the high-dose group). Significant reduced ossification in nasal frontal, parietal, interparietal, caudal, and tarsal bones were observed only in the 152.4 mg chromium(VI)/kg/day-treated animals


Justification for selection of Effect on developmental toxicity: via oral route:
Based on the review of available information by the European Food Safety Authority.

Justification for classification or non-classification

Based on the available information and in accordance with the EU-classification, C.I. Pigment Yellow 34 should be considered as toxic to reproduction and the development, in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC (DSD: Repr. Cat. 1; R61 and Repr. Cat. 3; R62, CLP: Repr. 1A; H360Df).