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Diss Factsheets
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EC number: 701-394-3 | CAS number: 1782069-81-1
- 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:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- The dermal absorption factor is reported from a regulatory opinion document from the Scientific Committee on Consumer Products (SCCP). The dermal absorption factor considered in this opinion is used to determine the Margin of Safety (MoS) of 4-methylbenzylidene camphor in sunscreens.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 428 (Skin Absorption: In Vitro Method)
- Version / remarks:
- 1994, draft
- Qualifier:
- according to guideline
- Guideline:
- other: COLIPA Guideline for Percutaneous Absorption/Penetration
- Version / remarks:
- 1995
- GLP compliance:
- not specified
- Remarks:
- Study is summarised in a regulatory opinion document; full study details are not available
- Radiolabelling:
- no
- Species:
- pig
- Sex:
- female
- Type of coverage:
- not specified
- Duration of exposure:
- 24 hours
- Doses:
- 167 to 200 μg test item/cm², corresponding to 4.5 mg formulation/cm² of a 4% test item formulation
- No. of animals per group:
- 8 experiments, performed in triplicate
- Details on study design:
- SAMPLE COLLECTION
- Skin surface: Gentle scraping with a spatula and/or threefold wiping with cotton wool (corresponds to non-absorbed sample)
- Horny layer: About 15-20 fold stripping with self-adhesive "tesa-film" tape
- Epidermis: Heating of the skin disc (epidermal side for 45 seconds on a 80°C hot plate (Ceram), separation epidermis from dermis with forceps)
- Dermis: 3 punched samples or total dermis
- Receptor fluid: 2 aliquots
ANALYSIS
- Method type(s) for identification: HPLC-DAD
- Limits of detection and quantification: LOD: approximately 0.03 μg/mL, LOQ: approximately 0.1 μg/mL - Details on in vitro test system (if applicable):
- SKIN PREPARATION
- Source of skin: Pig
- Type of skin: Unboiled back skin
- Preparative technique: Skin discs (gently dry-shaved surface, diameter 5 cm)
- Thickness of skin: 3-4 mm
PRINCIPLES OF ASSAY
- Diffusion cell: Glass penetration cell
- Receptor fluid: 0.9% sodium chloride, 1% bovine serum albumin and 0.02% gentamycine sulphate in water
- Solubility of test substance in receptor fluid: Receptor fluid suitable for hydrophilic and lipophilic samples
- Test temperature: 32°C - Signs and symptoms of toxicity:
- not specified
- Dermal irritation:
- not specified
- Absorption in different matrices:
- No test item was detected in the receptor fluid.
- Total recovery:
- Mean total recovery was 91.8% (range 86.8 to 95.6%).
- Key result
- Time point:
- 24 h
- Dose:
- 178 μg/cm²
- Parameter:
- percentage
- Remarks:
- 1.96 μg/cm² (epidermis+dermis)
- Absorption:
- 1.1 %
- Remarks on result:
- other: mean of 8 experiments
- Conclusions:
- Taking into account the values obtained in eight separate experiments, the SCCP consider a mean dermal absorption value of 1.96 μg/cm² as the basis to determine safe use for 4-methylbenzylidene camphor in sunscreen formulations. Based on a mean applied amount of 178 μg/cm², the dermal absorption factor is calculated to be 1.10% (epidermis+dermis).
- Executive summary:
Data on the dermal absorption of 4 -methylbenzylidene camphor is available in a regulatory opinion document from the Scientific Committee on Consumer Products (SCCP). Taking into account the values obtained in eight separate in vitro experiments using pig skin, the SCCP consider a mean dermal absorption value of 1.96 μg/cm² as the basis to determine safe use for 4-methylbenzylidene camphor in sunscreen formulations. Based on a mean applied amount of 178 μg/cm², the dermal absorption factor is calculated to be 1.10% (epidermis+dermis). The reliability of this data source cannot be assigned (Klimisch 4) as it is a secondary source reporting from a summary of eight individual experiments. The original studies were not obtained for reliability and relevance assessment, however as the data is used in a regulatory opinion, it is assumed to be sufficiently reliable.
Reference
Table 1. Summary of dermal absorption rates
Test | Applied substance (μg/cm²) | Surface (μg/cm²) | Horny layer (μg/cm²) | Epidermis (μg/cm²) | Dermis (μg/cm²) | Recovery (%) |
1 | 182 | 125 | 38.2 | 2.0 | 0.34 | 90.9 |
2 | 200 | 159 | 26.2 | 1.3 | 0.50 | 93.8 |
3 | 172 | 132 | 27.6 | 2.4 | 0.72 | 94.7 |
4 | 175 | 119 | 31.0 | 1.7 | 0.90 | 87.2 |
5 | 171 | 138 | 23.5 | 0.7 | 0.34 | 95.0 |
6 | 167 | 132 | 16.2 | 1.4 | 0.88 | 90.0 |
7 | 187 | 144 | 17.1 | 0.4 | not detectable | 86.8 |
8 | 173 | 140 | 23.5 | 2.2 | not detectable | 95.6 |
Mean | 178 | 136 | 25.4 | 1.5 | 0.46 | 91.8 |
Standard deviation | 11 | 12.5 | 7.2 | 0.7 | 0.36 | 3.5 |
Description of key information
In a study by Schauer et al (2006), plasma levels and toxicokinetics were investigated in both human subjects and rats following dermal exposure:
The toxicokinetics of 4-methylbenzylidene camphor after dermal administration were investigated in humans. Humans (3 male and 3 female subjects) were exposed to 4-MBC by topical application of a commercial sunscreen formulation containing 4% 4-MBC (w/w), covering 90% of the body surface and resulting in a mean dermal 4-MBC dose of 22 mg/kg bw. Concentrations of 4-MBC and its metabolites were monitored over 96 h in plasma and urine. Peak plasma levels (Cmax) of 4-MBC were reached 6 h after dermal application (200 pmol/mL in males and 100 pmol/mL in females). After the 6 h sampling point, 4-MBC concentrations decreased following 1st order kinetics with a half-life of 9 h to reach the limit of quantitation at 48 h (males) or 36 h (females) after the application. The AUC values were 3884 and 1909 pmol/mL h in males and females, respectively. In plasma, 3-(4-carboxybenzylidene)camphor is the major metabolic product, whereas, in urine, 3-(4-carboxybenzylidene)-6-hydroxycamphor and a glucuronide of 3-(4-carboxybenzylidene)camphor are major metabolites. Less than 1% of the applied dose of 4-MBC was recovered in urine as metabolites.
The toxicokinetics of 4-methylbenzylidene camphor after dermal administration were investigated in rats. Wistar rats (3 male and 3 female subjects) were exposed to dermal 4-MBC doses of 400 and 2000 mg/kg bw applied in a formulation using an occlusive patch for 24 h. Concentrations of 4-MBC and its metabolites were monitored over 96 h in plasma. Peak plasma levels of 4-MBC were 200 (dose of 400 mg/kg bw) and 1200 pmol/mL (dose of 2000 mg/kg bw) in male and female rats. These levels remained constant for up to 24–48 h after dermal application. Two major metabolites were identified in the plasma of rats after dermal application: 3-(4-carboxybenzylidene)-6-hydroxycamphor and 3-(4-carboxybenzylidene)camphor.
In an opinion document on 4-MBC by the Scientific Committee on Consumer Products (SCCP, 2008) a toxicokinetic approach was used to derive a Margin of Safety (MoS) for 4-MBC. A mean dermal absorption value of 1.96 μg/cm² from an applied substance amount of 178 μg/cm² yielded a calculated dermal absorption value of 1.10%.
Key value for chemical safety assessment
- Absorption rate - oral (%):
- 50
- Absorption rate - dermal (%):
- 1.1
- Absorption rate - inhalation (%):
- 100
Additional information
The study by Schauer et al. (2006) concluded that the biotransformation of 4-MBC in humans and rats after dermal administration is identical and occurs by a series of cytochrome P450-catalyzed oxidations of 4-MBC followed by formation of glucuronides. Also the kinetics following dermal exposure to 4-MBC was considered to be similar between rats and humans with peak plasma levels being reached approximately 6 hours following the exposure and plasma levels regressing towards the limit of quantification at around 48 hours post-exposure. As no new dermal absorption studies have been identified with adequate reliability, a dermal absorption factor of 1.10% is used in line with the current regulatory opinion (SCCP 2008).
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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