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EC number: 248-315-4 | CAS number: 27194-74-7
- 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
Description of key information
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 08 July 2015 to 28 January 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study performed in an accredited GLP compliant laboratory according to current OECD test Guidelines
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
A read-across approach has been suggested based on the metabolism of the common structure of propylene glycol fatty acid esters. Read-across is implemented from already existing data from testing on Dapro FX511, on metabolism products (fatty acid and propylene glycol) and on propylene glycol monolaurate.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical:
Dapro FX 511
EC Number: 285-503-5
CAS Number: 85114-00-7
Target chemical:
RM1004755:
Einecs No. 248-315-4
CAS No. 27194-74-7
See read-across justification report in section 13
3. ANALOGUE APPROACH JUSTIFICATION
A matrix of data has been created using the Dapro FX511 REACH dossier, read-across document for aquatic tox from Dapro FX510 (source) to Dapro FX511 (target), a HPV test plan for the glycol esters of the aliphatic esters chemicals (including Propylene glycol, monostearate (CAS 1323-39-3)) and a Petition to include propylene glycol monolaurate into 7 CFR 205 (constituent of RM1004755).
See read-across justification report in section 13
4. DATA MATRIX
Data matrix is given in read-across justification report in section 13
- Name of test material (as cited in study report): SER-AD FX 511
- Physical state: liquid (colourless, slightly viscous)
- Analytical purity: no data; the purity of the test material was the responsibility of the sponsor
- Storage condition of test material: room temperature - Reason / purpose for cross-reference:
- read-across source
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- slight effect of treatement at 1000 mg/kg/day
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- There were no ophthalmic findings that were considered to be related to treatment
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- Sensory reactivity responses, grip strength and motor activity were unaffected by treatment
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- An increase in absolute and body weight adjusted liver and kidney weights in males and females
given 500 or 1000 mg/kg/day, attaining statistical significance in the majority of the body weight
adjusted groups. - Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Changes in the kidneys of male rats only considered test-item related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- Test item-related effects on the cortex of the kidney consisted of minimal to moderate hyaline droplets, as intracytoplasmic droplets and eosinophilic inclusion round bodies surrounded by a clear halo on males receiving 250 mg/kg/day or above, although one control male was also observed with this change. Many xenobiotics bind to alpha-2u-globulin and decrease effectiveness of lysosomal degradation in male rats. These findings are likely to be alpha-2u-globulin nephropathy, which is a sex and species specific entity. In addition, minimal to slight tubular basophilia with interstitial fibrosis was recorded in males given 250, 500 and 1000 mg/kg/day, which was predominantly characterized by multifocal clusters of basophilic tubules, nuclear crowding, tubular dilatation, interstitial inflammator y cell infiltrates and thickening of the basal membranes (demonstrated by the PAS stain), which in one male progressed to tubular necrosis. These findings correlated with increased kidney weights and increased levels of urea in males given 500 or 1000 mg/kg/day after 13 weeks of treatment. The test item changes observed in the kidneys were considered adverse in males given 500 or 1000 mg/kg/day as the findings reflected dose-dependent changes that correlated with elevated urea and increased
kidney weights.
In the liver, minimal centrilobular eosinophilia/hypertrophy was observed in males and females given 1000 mg/kg/day and females given 500 mg/kg/day. This finding correlated with increased liver weights in both males and females after 13 weeks of treatment and was expected for this compound class. The test item, RD 15134 (2-Ethylhexanoic acid, monoester with propane 1,2–diol) is related to ethyl hexanoic acid, which is considered a peroxisome proliferator that typically produces hypertrophy of the centrilobular hepatocytes due to the increase of the volume of peroxisomes, accompanied by lipid reduction and increased liver weights (Sundberg et al., 1994; Keith et al., 1992). There are considerable species differences in sensitivity to peroxisomal proliferation and humans appear to be less susceptible to many peroxisomal proliferators (Chevalier et al., 1998). The test-item related changes in the liver were not considered adverse as these changes represented an adaptive response.
The changes in the thyroid are considered secondary to the induction of liver metabolism enzymes. There was an increased incidence of minimal follicular cell hypertrophy observed in all treated groups, with a higher incidence in the males. The incidence in the males given 500 mg/kg/day was slightly higher than 1000 mg/kg/day, which reflects a degree of biological variation between treated males. Some studies have shown that peroxisome proliferators lead to enzymatic induction in the liver, which can induce increased breakdown of thyroid hormones and also displace thyroid hormones from serum carrier proteins. This will consequently lead to lower circulating levels of thyroid hormones, resulting in a release from negative feedback inhibition and compensatory increased secretion of TSH from the pituitary gland, resulting in follicular cell hypertrophy in the thyroid (Richardson and Klaasen, 2010, Miller et al., 2001). Again, there are considerable species differences in thyroid hormone synthesis, transport and metabolism between rodents and humans. The thyroid changes are not considered adverse as the follicular cell hypertrophy
reflects a rodent specific adaptive response.
In the absence of histopathological correlate the following changes were not considered to be of toxicologically significance; the decrease in haematocrit, haemoglobin concentration and red blood cells counts in males receiving 250, 500 or 1000 mg/kg/day, a decrease in haematocrit and h
aemoglobin concentration in females at 1000 mg/kg/day. In addition, there was no correlate for low mean cell haemoglobin and mean cell volume in females receiving 500 or 1000 mg/kg/day and changes were seen in neutrophils, lymphocytes, and basophils, with an associated reduction in
overall low white blood cell count or the low large unstained stain cell counts or shorter activated partial thromboplastin time in females receiving 1000 mg/kg/day. Similarly, total protein and albumin concentration were low in treated males, with an associated high A/G ratio in high dose males were not considered to be toxicologically significant. - Dose descriptor:
- NOAEL
- Effect level:
- 250 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Based primarily on the changes seen in the kidney
- Remarks on result:
- other: Based primarily on the changes seen in the kidneys
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No test substance effects seen at 1000 mg/kg bw/day the highest dose level tested
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- System:
- urinary
- Organ:
- kidney
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
- Conclusions:
- It is concluded that oral administration of RD 15134, a coalescing agent, to Sprague-Dawley Crl:CD(SD) rats at 250, 500 or 1000 mg/kg/day for 13 weeks was relatively well-tolerated at doses in males at 250 mg/kg/day and in females up to 1000 mg/kg/day. In males, a dose of 500 mg/kg/day or above resulted in hyaline droplets and tubular basophilia with interstitial fibrosis in the kidney, with an associated increase in kidney weight and urea concentration.
It is therefore considered that the no-observed-adverse- effect-level (NOAEL) was 250 mg/kg/day in males, based primarily on the changes seen in the kidneys, and 1000 mg/kg/day in females.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 250 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) conducted in 2015 with no deficiencies and assigned Klimisch 1
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
It is concluded that oral administration of RD 15134 (the read-across analogue for RM1004755), also a coalescing agent, to Sprague-Dawley Crl:CD(SD) rats at 250, 500 or 1000 mg/kg/day for 13 weeks was relatively well-tolerated at doses in males at 250 mg/kg/day and in females up to 1000 mg/kg/day. In males, a dose of 500 mg/kg/day or above resulted in hyaline droplets and tubular basophilia with interstitial fibrosis in the kidney, with an associated increase in kidney weight and urea concentration. It is therefore considered that the no-observed-adverse-effect-level (NOAEL) was 250 mg/kg/day in males based primarily on the changes seen in the kidneys and 1000 mg/kg/day in females.
Justification for classification or non-classification
RM1004755 is not classified for specific organ toxicity, repeated exposure, as the NOAEL of the read-across analogue (RD 15134) in male rats is 250 mg/kg/day, according to CLP 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.
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