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EC number: 203-817-2 | CAS number: 110-94-1
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
The toxicity to fertily of the registered substance was assessed using literature data on the substance and on an analogous substance. No study investigating the toxicity of the substance to reproduction was identified, but the effects of the substance to reproductive organs was investigated as part of unpublished subchronic repeated-dose toxicity studies on rats and dogs respectively. No significant adverse effect was identified. As rats are considered the more relevant species for reproductive toxicity testing than dogs, it is proposed to use a NOAEL(fertility) of 1,720 mg/kg bw/day of glutaric acid for male rats and 1,960 mg/kg bw/day for female rats obtained during the subchronic repeated-dose toxicity study performed on rats, as they were the highest dose evaluated and did not induce significant adverse effects. These values are supported by the results of the subchronic repeated-dose toxicity study performed on dogs using the registered substance and the chronic toxicity study on rats using the analogous substance adipic acid.
The developmental toxicity of the registered substance was assessed using literature data on the substance and on an analogous substance. Two unpublished studies were identified investigating the developmental toxicity on the registered substance, performed on rats and rabbits respectively. The only significant adverse effects observed was an increase of the number of resorptions at 1,300 mg/kg bw/d in rats, which was the highest dose investigated and was above the limit of 1,000 mg/kg bw/d recommended by the OECD Testing Guideline 414. Two developmental toxicity studies were performed on the analogous substance adipic without identifying adverse effects at up to 250 mg/kg bw/d in rabbits, 288 mg/kg bw/d in rats, 263 mg/kg bw/d in mice, and 205 mg/kg bw/d. None of these doses induced maternal toxicity. Rabbits being the most relevant species for this endpoint, it is proposed to set a NOAEL for maternity toxicity and a NOAEL for developmental toxicity of 250 mg/kg bw/day considering that these values are conservative compared to the results obtained on the registered substance.
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- other: expert assessment
- Adequacy of study:
- weight of evidence
- Study period:
- 14 December 2016
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: An assessment was performed based on literature data on the substance and literature data on an analogous substance.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- An assessment was performed based on literature data on the substance and literature data on an analogous substance.
- GLP compliance:
- no
- Limit test:
- no
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- fertility
- Effect level:
- 1 720 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- gross pathology
- histopathology: non-neoplastic
- Dose descriptor:
- NOAEL
- Remarks:
- fertility
- Effect level:
- 1 960 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- gross pathology
- histopathology: non-neoplastic
- Remarks on result:
- not measured/tested
- Critical effects observed:
- no
- Key result
- Reproductive effects observed:
- no
- Conclusions:
- As the conclusion of this assessment, it is proposed to use a NOAEL(fertility) of 1,720 mg/kg bw/day of glutaric acid for the male rats and 1,960 mg/kg bw/day for the female rats as they represent a worst-case scenario compared to the values derived from the chronic study on adipic acid (the value derived from the evaluation of adipic acid on female rats was not considered due to the low concentration tested).
With regard to the pre-natal developmental toxicity, the NOAEL(maternity toxicity) and NOAEL(developmental toxicity) of 250 mg/kg bw/day obtained on rabbits with adipic acid could be considered as representing a worst-case scenario as they were the highest concentrations tested and did not induce any observable effects. This approach is considered as conservative, as higher NOAELs were derived from a pre-natal developmental toxicity study performed on glutaric acid and deemed as reliable by US EPA (2001). - Executive summary:
The reproductive toxicity of glutaric acid was assessed using a read-across from the analogous substance adipic acid supported by available experimental data on glutaric acid.
Horn et al. (1957) investigated the effects of adipic acid on the sexual organs of rats as part of a chronic study. When tested up to concentrations of 5% in diet for males and 0.1% for females, equivalent respectively to 3,450 mg/kg bw/day for the males and 80 mg/kg bw/day for the females, adipic acid did not induce observable effects to the sexual organs,. These values may be used to derive the NOAEL(fertility) of adipic acid: 3,450 mg/kg bw/day for the males and 80 mg/kg bw/day for the females. However, the result for female rats cannot be considered as relevant since the highest concentration tested was only 0.1% of adipic acid in diet.
Litton Bionetics, Inc. (1973, 1974) performed developmental toxicity studies on adipic acid using a method similar to OECD Testing Guideline 414 with deviations. Studies were performed on rats, rabbits, mice, and hamsters, with the one on rabbits being considered as the most relevant and conservative. It allows to obtain a NOAEL(maternity toxicity) and a NOAEL(developmental toxicity) of 250 mg/kg bw/day of adipic acid, as it was the highest concentration tested in rabbits and did not induce observable adverse effects.
These results were supported by the historical uses of adipic acid in foodstuff, feed and industrial processes.
The experimental data on adipic acid are supported by the consistent results obtained from two subchronic studies on glutaric acid performed by Solutia Inc. (1977a, 1977b) and two pre-natal developmental toxicity studies performed by Sterling-Winthrop Research Institute (1984) and used as a weight of evidence for the purpose of this assessment.
Effects of glutaric acid on sexual organs was investigated as part of the subchronic studies. The substance was tested up to concentrations of 2% in the diet in male and female rats, and up to 5% in diet in male and female dogs without inducing any observable adverse effects to the sexual organs. Results from the subchronic study on rats were considered for the purpose of deriving the NOAEL(fertility) as rats represent a more relevant species for the purpose of this evaluation. Therefore, it is proposed a NOAEL(fertility) of 1,720 mg/kg bw/day of glutaric acid for the males and 1,960 mg/kg bw/day for the females.
Pre-natal developmental toxicity of glutaric acid was investigated on rats and rabbits, which are the most relevant species for the purpose of this evaluation. Based on the results of these studies it is proposed to use a NOAEL(maternal toxicity) and a NOAEL(developmental toxicity) of 400 mg/kg bw/day as they are representing a worst-case scenario.
These results are supported by the fact that glutaric acid is naturally produced in the human body during the metabolisation of several amino acids.
As the conclusion of this assessment, it is proposed to use a NOAEL(fertility) of 1,720 mg/kg bw/day of glutaric acid for the male rats and 1,960 mg/kg bw/day for the female rats as they represent a worst-case scenario compared to the values derived from the chronic study on adipic acid (the value derived from the evaluation of adipic acid on female rats was not considered due to the low concentration tested).
With regard to the pre-natal developmental toxicity, the NOAEL(maternity toxicity) and NOAEL(developmental toxicity) of 250 mg/kg bw/day obtained on rabbits with adipic acid could be considered as representing a worst-case scenario as they were the highest concentrations tested and did not induce any observable effects. This approach is considered as conservative, as higher NOAELs were derived from a pre-natal developmental toxicity study performed on glutaric acid and deemed as reliable by US EPA (2001).
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 720 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- An assessment was performed based on literature data on the substance and literature data on an analogous substance.
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Effects on developmental toxicity
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
The toxicity to fertily of the registered substance was investigated using information on the effects on reproductive organs induced by the registered substance and the analogous susbtance adipic acid. No significant adverse effects were identified.
The pre-natal developmental toxicity of the registered substance was investigated using studies performed on the registered substance and the analogous substance adipic acid. The only significant adverse effects observed was an increase of the number of resorptions in rats treated at 1,300 mg/kg bw/d of the registered substance, a dose above the limit dose of 1,000 mg/kg bw/d recommended by the OECD Testing Guideline 414.
It is concluded that the registered substance does not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.
Additional information
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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