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Diss Factsheets
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EC number: 201-851-2 | CAS number: 88-68-6
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics, other
- Type of information:
- other: Expert review and assessment
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Not assignable as the result is from expert assessment.
Data source
Reference
- Reference Type:
- other company data
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
- Objective of study:
- other: Basic toxicokinetic assessment to support REACH Annex VIII registration.
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Expert review of available data.
- GLP compliance:
- no
Test material
- Reference substance name:
- Anthranilamide
- EC Number:
- 201-851-2
- EC Name:
- Anthranilamide
- Cas Number:
- 88-68-6
- Molecular formula:
- C7H8N2O
- IUPAC Name:
- 2-aminobenzamide
- Test material form:
- solid: particulate/powder
- Remarks:
- tan
Constituent 1
Results and discussion
Any other information on results incl. tables
INFORMATION BASED ON PHYSICO-CHEMICAL PROPERTIES
Anthranilamide is a benzamide derivative with a molecular weight of 136.15. It is a solid at room temperature and has a melting point of 110 – 115°C. The substance has only limited solubility in water at 16.6 g/l at 20 °C. The log Pow is 0.76 at 25°C which indicates that the substance will have some limited solubility in lipids.
In its solid form Anthranilamide is a crystalline powder. Particle size analysis found that 36.67% of the particles are inhalable (particle size <100 µm), but that 0% were < 4 µm and therefore the sample was not considered to contain respirable particles.
There is no hydrolysis data on Anthranilamide as the REACH Annex VIII test was waivered due to Anthranilamide being readily biodegradable.
ABSORPTION, DISTRIBUTION AND EXCRETION
Absorption
Potential for Absorption
Anthranilamide in solid form contains 36.67% particles of a size that could be inhaled following exposure to airborne dusts. However as 0% of particles are respirable, little of an inhaled dose will reach the alveoli and most of the dose can be expected to be transferred to the stomach via mucocilliary action and swallowing.
Anthranilamide is a low molecular weight molecule and therefore its size is unlikely to present a significant barrier to absorption across the gastrointestinal mucosa, hence, uptake as it passes through the gastrointestinal tract may occur. Anthranilamide uptake is likely to vary as it passes through the gut given that it will be ionised to differing degrees at the different pH’s encountered in the gastrointestinal tract. Anthranilamide has a log P value of 0.76 and therefore the non-ionised form is likely to have sufficient lipid solubility to pass across biological membranes. It is unlikely that active transport mechanisms will be a significant uptake route due to a lack of similarity with endogenous molecules.
Overall, it can be expected that absorption of the intact molecule across the gastrointestinal mucosa will occur, but a proportion of an oral dose is likely to not be absorbed and subsequently be excreted in the faeces.
Evidence for Absorption
An oral repeated dose reproductive developmental toxicity screening study has been conducted on Anthranilamide using doses of 30, 150 and 500 mg/kg/bw/day. There were some clear systemic toxicological effects in the study at 500 mg/kg bw/day and on offspring development at 150 and 500 mg/kg bw/day indicating thatAnthranilamide was absorbed and it, or its metabolites were at a sufficient concentration to exert effects.
There is no information on which to assess with certainty if Anthranilamide can be absorbed significantly via dermal exposure. Given its molecular weight it is conceivable that a dermal absorption could occur; however, factors such as its relatively low lipid solubility are likely to mean that absorption by this route is unlikely to be significant.
DISTRIBUTION
It is unlikely that Anthranilamide will exhibit any significant distribution within the body between plasma and tissues as its logP value (0.76) does not indicate it will have a strong affinity for fats.
Minor developmental effects consisting of reductions in offspring body weight, body weight gains and general development were seen in the oral repeated dose reproductive developmental toxicity screening study. Effects were seen at doses below those which maternal toxicity occurred; however, it is not possible to draw any conclusions from the study about whether the effect was due to a direct action on the offspring and/or reproductive system and concomitantly conclusions cannot be drawn about whether the distribution of Anthranilamide in the body includes the reproductive organs.
METABOLISM
Anthranilamide contains a water solubilising hydroxyl group which is likely to aid excretion and also metabolism of the molecule by cytochrome P450 enzyme metabolising system. Additionally, amine groups on the molecule are likely to undergo oxidation by amine oxidase enzymes. Hence, in organisms such as mammals and fish with significantly developed xenobiotic metabolising systems, Anthranilamide is expected to undergo a degree of metabolism resulting in breakdown of the molecule and ultimate excretion.
Reports in the literature indicate that Anthranilamide is metabolised principally to 3-hydroxy Anthranilamide-O-sulphate and 5-hydroxyanthrilamide-O-sulphate.[1] Anthranilamide is a metabolite of anthranilic acid and studies reported in the literature on the metabolism of anthranilic acid in mammals indicate that Anthranilamide generated from the metabolism of anthranilic acid is further metabolised so that only a small proportion (=<5%) of a dose could be detected as free Anthranilamide[2].
In two in vitro bacterial reverse mutation assay using S. typhimurium and E. coli, and an in vitro mammalian chromosome aberration assay in Chinese Hamster Ovary cells, Anthranilamide gave negative results in both the presence and absence of an S9 metabolising system. Given the negative results, no conclusions about the potential of Anthranilamide to undergo metabolic change can be drawn from these studies.
Excretion
Due to addition of water solubilising groups during metabolism the main route of excretion of absorbed Anthranilamide and/or its metabolites is likely to be via the kidneys into the urine. The molecular weight of Anthranilamideis below the biliary exclusion limit of circa 325 in the rat and 500 in humans and therefore elimination of any absorbed substance in the bile is not expected to be significant.
[1]D E Hathway (Editor), Foreign Compound Metabolism in Mammals, Volume 5, 1979, Publisher: The chemical Society.
[2]Tjang Mushadji Sutamihardjaet al, Studies on the New Metabolic Pathway of Anthranilic Acid in the Rat I. Isolation and Urinary Excretion of Anthranilamide as a New Metabolite of Anthranilic Acid. Chem. Pharm. Bull, 20(12) 264-2700 (1972).
Applicant's summary and conclusion
- Conclusions:
- An assessment of the potential absorption of Anthranilamide based on its physico-chemical properties suggest that absorption across the gastrointestinal mucosa will occur although it likely to be slow and part of an oral dose can be expected to be excreted in the faeces. However, a proportion will be systemically absorbed as demonstrated by the observation of treatment related effects in a repeat dose toxicity and reproductive developmental toxicity screening study (OECD 422) conducted on the Anthranilamide.
The presence of a hydroxyl group on the structure can be expected to aid metabolism of systemically, absorbed Anthranilamide to water soluble products that will ultimately be excreted via the kidneys.
There is no expectation that Anthranilamide will preferentially distribute to particular organs or tissues in the body. - Executive summary:
Introduction
An expert review of the toxicokinetic profile of the test substance was undertaken based on its physiciochemical profile and available data from toxicolgical studies.
Conclusion
An assessment of the potential absorption of Anthranilamide based on its physico-chemical properties suggest that absorption across the gastrointestinal mucosa will occur although it likely to be slow and part of an oral dose can be expected to be excreted in the faeces. However, a proportion will be systemically absorbed as demonstrated by the observation of treatment related effects in a repeat dose toxicity and reproductive developmental toxicity screening study (OECD 422) conducted on the Anthranilamide.
The presence of a hydroxyl group on the structure can be expected to aid metabolism of systemically, absorbed Anthranilamide to water soluble products that will ultimately be excreted via the kidneys.
There is no expectation that Anthranilamide will preferentially distribute to particular organs or tissues in the body.
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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