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EC number: 292-966-7 | CAS number: 91031-62-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
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Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- dermal absorption in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 428 (Skin Absorption: In Vitro Method)
- GLP compliance:
- yes
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): Lead Oxide
- Supplier: EBRC Consulting GmbH, Zeppelinstrasse 8, D-30175 Hannover, Germany
- Substance type: Solid
- Physical state: Yellowish powder
- Analytical purity: 99.8%
- Batch No.: 210213
- Stability under test conditions: 2 years
- Storage condition of test material: Ambient temperature in the dark - Radiolabelling:
- no
- Species:
- other: human
- Type of coverage:
- open
- Vehicle:
- other: 1% hydroxypropylmethyl cellulose in water
- Duration of exposure:
- 6 hours, with an additional 18 hour monitoring period
- Doses:
- - Nominal doses: 0, 100, and 1000 ug/cm2
- Actual doses: 0, 111, and 1033 ug/cm2 - Details on study design:
- Test preparations (7.6 uL) were applied over the surface of the stratum corneum of exposed skin. At 6 hours post-exposure, skin was washed with a 2% soap solution and then dried with tissue swabs. At 24 hours post-exposure, each diffusion cell was disconnected and the underside of the skin was rinsed with receptor fluid. The skin was removed and the donor and receptor chambers were transferred into separate pots of receptor fluid and test items were extracted for 30 minutes. The skin was dried and the stratum corneum was removed with 25 successive tape strips, which were pooled into vials. Throughout the study, receptor fluid was collected in four fractions (0-6 hours, 6-12 hours, 12-18 hours, and 18-24 hours). All samples were analyzed for lead concentration by Harwell Scientifics using ICP-MS.
- Details on in vitro test system (if applicable):
- SKIN PREPARATION
- Source of skin: 40-year-old patient undergoing routine surgery
- Ethical approval if human skin: Informed consent received
- Type of skin: A single, full-thickness human breast skin sample
- Preparative technique: Split-thickness membranes prepared by pinning the skin, with the stratum corneum up, onto a raised corkboard and cutting at a setting of 200-400 um depth using a Zimmer electric dermatome.
- Thickness of skin: Split-thickness skin samples were 390-400 um thick
- Membrane integrity check: Assessed by penetration of tritiated water (250 uL) applied to skin surface with the donor chamber occluded. All skin samples with a tritiated water permeability coefficient (kp) less than 0.0025 cm/hour were accepted into the study.
- Storage conditions: Full-thickness skins were dried and stored at -20 degrees C. Split-thickness skins were used immediately after being cut.
PRINCIPLES OF ASSAY
- Diffusion cell: Automated flow-through diffusion cell apparatus (Scott/Dick, University of Newcastle-upon-Tyne, United Kingdom)
- Receptor fluid: Phosphate buffered saline containing 5% bovine serum albumin, Streptomycin, and Penicillin G, pH 7.4
- Flow-through system: Flow-through cells were connected to multi-channel peristaltic pumps from their afferent ports. The receptor chamber volume was 0.25 mL and the peristaltic pumps maintained a flow-rate of 1.5 mL/hour.
- Test temperature: 32 degrees C
- Occlusion: None; the chambers were left open to the atmosphere.
- Other: Surface area of exposed skin within diffusion cells was 0.64 cm2. - Signs and symptoms of toxicity:
- not specified
- Dermal irritation:
- not specified
- Absorption in different matrices:
- For the 111 ug/cm2 dose: 95.63% of the applied lead was removed during the wash at 6 hours post-exposure. At 24 hours post-exposure, 99.51% of the applied dose was not absorbed. The absorbed dose into the receptor fluid was <0.01% (5 ng/cm2) of the applied dose and the dermal delivery (absorbed dose plus the amount in the skin itself) was 0.13% (148 ng/cm2) of the applied dose.
For the 1033 ug/cm2 dose: 96.10% of the applied lead was removed during the wash at 6 hours post-exposure. At 24 hours post-exposure, 98.28% of the applied dose was not absorbed. The absorbed dose was < 0.01% (10 ng/cm2) of the applied dose and the dermal delivery was 0.05% (479 ng/cm2) of the applied dose. - Time point:
- 24 h
- Dose:
- 111 ug/cm2
- Parameter:
- percentage
- Absorption:
- ca. 0.13 %
- Time point:
- 24 h
- Dose:
- 1033 ug/cm2
- Parameter:
- percentage
- Absorption:
- ca. 0.05 %
- Conclusions:
- The authors concluded that the apparent decrease in absorption as a function of dose may be attributable to the considerable background from endogenous lead in the donor skin restricting the reliability of the absorption factor at the low dose.
- Executive summary:
This study assessed the in vitro absorption of lead oxide in human skin samples at 0, 111, and 1033 ug/cm2 concentrations over 24 hours. For the 111 ug/cm2 dose, 95.63% of the applied lead was removed during the wash at 6 hours post-exposure. At 24 hours post-exposure, 99.51% of the applied dose was not absorbed. The absorbed dose into the receptor fluid was <0.01% (5 ng/cm2) and the dermal delivery was 0.13% (148 mg/cm2) of the applied dose. For the 1033 ug/cm2 dose, 96.10% of the applied lead was removed during the wash at 6 hours post-exposure. At 24 hours post-exposure, 98.28% of the applied dose was not absorbed. The absorbed dose was <0.01% (10 ng/cm2) and the dermal delivery was 0.05% (479 ng/cm2) of the applied dose. The authors concluded that the apparent decrease in absorption as a function of dose may be attributable to the considerable background from endogenous lead in the donor skin restricting the reliability of the absorption factor at the low dose.
Reference
Description of key information
Note that observational studies in humans provide the basis for much of what is known about the toxicokinetics and toxicity of lead and are summarised in section 7.10. References to, and summaries of, the human data are made in the endpoint summaries of individual toxicological endpoints.
Short description of key information on absorption rate:
Dermal absorption of lead through unabraded human skin is considered to be minimal (<0 .1%) and thus absorption of inorganic lead compounds through the skin has previously been considered to be of less significance than absorption through the respiratory and gastrointestinal routes.
Key value for chemical safety assessment
Additional information
Animal studies serve to validate mechanistic inferences derived from observational human studies. The majority of information pertaining to lead toxicokinetics has been accurately defined in humans of different ages and degrees of susceptibility to lead toxicity. A number of toxicokinetic models have been developed to predict the effects of external lead exposure upon internal or systemic levels of lead. The Integrated Exposure Uptake Biokinetic (IEUBK) is now widely applied to assess relationships between environmental lead exposure and blood lead in children. Due to limitations in the ability of the IEUBK model to assess the deposition and subsequent remobilisation of lead from bone, use of the IEUBK model is generally restrict to predict exposures in chidren six years of age or younger.
Physiologically-based pharmacokineitc models (e.g. the O'Flaherty Model) have been developed to predict lead uptake in humans of all ages but is most commonly applied in the assessment of adult exposures. Both the O'Flaherty and IEUBK models are available as computer simulation models and are discussed in greater detail in section 7.10.5.
Lead is most easily taken up into the body through inhalation or ingestion – dermal uptake makes a negligible contribution to systemic lead levels. Once taken up into the body, lead is not metabolized. However, lead will distribute to a variety of tissue compartments such as blood, bone and soft tissues. The half-life of lead in the body varies as a function of body compartment. Lead in blood has a half life of 30 – 45 days – measurement of lead in blood thus provides an integrated assessment of average lead exposure (via all routes) over the preceding month. Lead is retained far longer in bones. Depending upon bone type, the retention time of lead can vary between 8 and 30 years. Such lead can both serve as a source of endogenous lead exposure and as a cumulative index of exposure over a time frame of years. Lead excretion is primary via urinary and biliary excretion routes.
Discussion on absorption rate:
Human data are available and superced the animals studies that have been conducted - one of which is described here. Detailed studies on dermal uptake in humans are described in section 7.10.5. Dermal absorption of lead through unabraded human skin is considered to be minimal and thus absorption of inorganic lead compounds through the skin has previously been considered to be of less significance than absorption through the respiratory and gastrointestinal routes. The most recent guideline-conformed in-vitro dermal absorption study (Toner and Roper, 2005) has established absorption of lead to be less than 0.1%. Other quantitative estimates of dermal absorption are limited in reliability with the most rigorous study (Moore et. al. 1980) suggesting uptake on the order of 0.01 – 0.18%. However, the data from many published studies on this aspect largely lack compliance with current guideline requirements, and their reliability and relevance for human health risk assessment is questionable.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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