Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 266-719-9 | CAS number: 67564-91-4
- 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
Neurotoxicity
Administrative data
Description of key information
Fenpropimorph did not cause neurotoxic effects in a neurotoxicity study after acute (gavage) oral feeding exposure in Wistar rats. After subchronic oral feeding effects on parameters of a functional observational battery (FOB) were observed (for details please refer to the chapter on repeated dose toxicity). In the acute study the clinical symptoms are in line with other acute studies in rats. The primary effect was a reduction on plasma cholinesterase and a minor reversible effect on brain cholinesterase but no effect on erythrocyte cholinesterase. In the subchronic neurotoxicity study there was only an effect on plasma cholinesterase as already known from subchronic studies in rats. A reduction of brain cholinesterase was observed only in a single oral study and could never been reproduced, this effect is of rather questionable certainty. After acute intraperitoneal administration in rats plasma cholinesterase (the only cholinesterase measured) was reduced as expected. No clear assessment on liver function/hepatotoxicity was possible due to concurrent peritonitis caused by the mode of administration.
In domestic hens, known to be very sensitive to neurotoxic agents no effect as determined by clinical symptoms and histopathology of the spinal cord/sciatic nerve was found even at doses ranging up to an LD50 in this species. There was no protective effect of PAM or atropine sulphate on mortality, indicating that death was not related to cholinesterase activity.
The toxicological significance and relevance of the decrease of cholinesterase in rats for the risk assessment for man should be addressed taking into account studies on kinetics and metabolism, standard toxicology studies and special neurotoxicity studies together.
From acute studies in rats it is known, that the onset of toxicity is delayed by 2 - 3 days. This does not indicate a direct effect of Fenpropimorph on cholinesterase inhibition but rather suggests the involvement of metabolites, which are formed after biotransformation of the parent compound. Several structural properties such as ammonium ions, a hydrophobic alkylarylmoiety and an ethanolamine group might be responsible for cholinesterase inhibition.
In the metabolic pathway of Fenpropimorph, a cleavage of the dimethylmorpholine ring system to form such structural properties is well known. It was demonstrated in in vitro experiments that structurally similar compounds to metabolites in which the dimethylmorpholin portion of the molecule has been opened and partly metabolised led to a decrease in plasma cholinesterase (see IUCLID chapter 7.9.4). Cis-Dimethylmorpholine itself, i.e. the intact structure of Fenpropimorph does not have this effect.
It is of importance to observe that the inhibition of plasma-acetyl-cholinesterase in vivo was only seen in rats. Since this species dependency may be caused by species differences in metabolism, an in vitro metabolism study has been carried out. In this study (for the RSS of the study, please refer to IUCLID chapter 7.1.1), a metabolic toxification could be proven by an increase of inhibition of plasma-acetyl-cholinesterase activity in the active incubates of microsomes versus the metabolically inactive control samples. Samples of purified incubates from liver slices demonstrated a metabolic toxification of fenpropimorph in rat liver slices only. This effect was not observed for mice and dogs. In the in vitro study, the main phase I metabolite in micsrosomes that was formed in all investigated species could be shown to be an inhibitor of plasma-acetyl-cholinesterase and therewith this metabolite may be responsible for the inhibitory effects of purified in vitro incubates. However, incubations in liver slices demonstrated that the main metabolite BF 421-1 is species dependently glucuronidized. The glucuronide BF 421-1-Gluc was predominantly formed in dogs and mice and only to a low extent in rats. Since BF 421-1 but not fenpropimorph itself inhibits plasma-acetyl-cholinesterase activity, the formation of BF 421-1 has to be considered a metabolic toxification. The further glucuronidation in mice and dogs can be concluded to be a subsequent detoxification, which reflects the species dependent enzyme inhibition in vivo.
The inhibition in vivo, either directly or indirectly observed, was not seen in mice, dogs, rabbits and hens in contrast to rats. The extreme species specific effect on the inhibition, combined with the fact that the cholinesterase inhibition is not related to a property of the technical active ingredient but rather to specific metabolites indicates that the metabolic toxification may be rat specific.
Thus the following conclusion can be drawn:
· there is no indication that Fenpropimorph or its metabolites have neurone damaging properties
· the effects on cholinesterase can be described as neuropharmacological
· the effect on plasma cholinesterase is reversible and comparable to the effect of choline
· the effect on plasma cholinesterase is only seen in rats
· rat specific metabolic toxification may cause this effect
· the effect on plasma cholinesterase seen in rats may not be relevant for risk assessment for man.
Key value for chemical safety assessment
Additional information
Justification for classification or non-classification
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.