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EC number: 202-785-7 | CAS number: 99-76-3
- 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
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
Additional information
Toxicokinetics
Several studies have been identified that examine the basic toxicokinetics of Methylparaben:
- Methylparaben was hydrolysed by both liver and skin microsomal/cytosolic fraction of humans and minipigs. The hydrolysis by human esterases was higher than that observed for minipigs.
- High plasma levels and urinary output of free and conjugated p-Hydroxybenzoic acid (metabolite of Methylparaben) in dogs indicate that hydrolysis of the ester linkage and metabolic conjugate constitute the main paths of alteration for Methylparaben. Excretion via urine is almost complete 48 hours after application of 100 mg/kg bw to dogs.
- 1 mg Methylparaben/kg bw/d was applied orally to a dog for one year. The rate of urinary excretion in the dog had increased to such an extent that after 24 hours 96% of the dose was recovered in the urine.
- Methyl p-hydroxybenzoate sodium salt was administered to rabbits (800 mg/kg bw/d) and urine collected for 24 hours was examined for metabolites. After application of a single dose Methylparaben to rabbits the main metabolites found in urine were p-Hydroxybenzoic acid, p-Hydroxyhippuric acid and the ether-type glucuronide.
- Groups of 12 male and 12 female rats received a single dermal administration of 100 mg/kg bw [14C]-labelled Methylparaben. The substance was completely metabolised to 4-Hydroxybenzoic acid. No systemic exposure was detected to Methylparaben 8 h after dermal application.
- After a single oral administration of 500 or 1000 mg/kg, Methyl 4-hydroxybenzoate, was rapidly absorbed with mean maximum plasma concentrations observed between 5 and 15 min post dosing. Afterwards, mean concentration-time profiles revealed a multiphasic behaviour with a rapid decline up to 1 hour and a plateau close to the detection limit between 1 and 8 hours. The course of the mean plasma concentrations did not allow extrapolation of the apparent terminal phase and thus, reliable estimation of t1/2 and AUC0-inf was not possible. Fast decline of plasma methyl parabens was accompanied by rapid onset of 4- Hydroxybenzoic acid indicating an efficient and comparable metabolism. In fact, 1 h after dosing mean plasma concentrations of methyl paraben had decreased to less than 10% of the maximum concentration. Furthermore, a substantial portion of the overall exposure was seen within the first hour after dosing.
Taking into account the results of all above mentioned ADME-studies, Methylparaben is considered to be rapidly metabolized to p-Hydroxybenzoic acid, which is conjugated to form the glucuronide rapidly and excreted completely within 24 hours after application. There is no tendency for bioaccumulation.
Dermal Absorption
Three dermal absorption studies were performed applying Methylparaben:
- The penetration kinetics and first-pass metabolism of Methylparaben in viable rat (n=10 replicates) and human skin (n=13 replicates) has been determined. The active ingredient was formulated as oil-in-water emulsion at a target concentration of 0.8% and 0.4%. rat and human skin. Penetration was followed using [14C]-labeled active ingredient. The amount of active applied per area skin was approx. 65 µg/cm2and 36 µg/cm2. Following application of a 0.8% Methylparaben emulsion to viable rat and human skin, a greater amount of total radioactivity penetrated human skin (79.36%) compared to rat skin (54.94%). A major portion of the total radioactivity that had penetrated rat skin was metabolised to 4-Hydroxybenzoic acid (53.9%), with a smaller portion (23.8%) accounted for as unmetabolised Methylparaben. By comparison, a lesser portion of the total radioactivity that had penetrated viable human skin had been metabolised to 4-Hydroxybenzoic acid (35.1%), with the majority (60.3%) accounted for as unmetabolised Methylparaben.
- 24 hours after the application on human skin (25 µg/cm2) 33.4% of the applied Methylparaben was absorbed; the surface wash removed unabsorbed Paraben, which was 11.5% of the applied dose. The skin was analysed for Methylparaben and a level of 28.6% was recovered. 24 hours after application to minipig skin, 38.6% of the applied Methylparaben had been absorbed; the skin surface wash contained about 13.4%. 23.9% Methylparaben were extracted from the skin. The metabolite 4-Hydroxybenzoic acid was found in the receptor fluid: 18.1% of the applied amount was found.
- Methylparaben penetrated the dorsal guinea pig skin via non-polar stratum corneum lipid lamella as a rate limiting step for skin penetration. The enhancers tested increase skin penetration of Methylparaben by increasing the fluidity of stratum corneum lipid lamella, which seems to lead to the increase of diffusion coefficient of the test item.
Methylparaben data:
- log K(p) full thickness (dorsal Guinea pig) skin: -0.9 cm/h
- log (p) lipid depleted (dorsal Guinea pig) skin: -2.25 cm/h
The addition of 1% l-Menthol in 15 % Ethanol increased the permeability coefficient of Methylparaben about 16 times. A similar, though weaker, tendency was observed in the presence of 15 % Ethanol itself without l-Menthol. N-dodecyl-2-pyrrolidone stimulated permeation of relatively hydrophilic Methylparaben.
From these data can be concluded that Methylparaben penetrates human as well as rat and minipig skin. Up to 79 % of the applied amount is absorbed. Up to 35 % of the absorbed substance is metabolised to p-Hydroxybenzoic acid.
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