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EC number: 906-256-8 | CAS number: -
- 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
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 70 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA guidance with modification to interspecies factor
- Overall assessment factor (AF):
- 10
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 700 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- There is no inhalation study, so the NOAEL for oral dosing is used as a starting point with route to route extrapolation. The starting point is a NOAEL of 100mg/kgbw/day from a sub-chronic study in rats. Assuming a 70kg person and a inhaled volume of 10m3/8hr working day and 100% absorption, this equates to a NOAEC of 700mg/m3 (theoretical concentration).
- AF for dose response relationship:
- 1
- Justification:
- default
- AF for differences in duration of exposure:
- 2
- Justification:
- default for sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- default for inhalation study
- AF for other interspecies differences:
- 1
- Justification:
- no additional factor is required.
- AF for intraspecies differences:
- 5
- Justification:
- default
- AF for the quality of the whole database:
- 1
- Justification:
- default
- AF for remaining uncertainties:
- 1
- Justification:
- default
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 33.5 mg/m³
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
- DNEL derivation method:
- other: data from human volunteer studies
- Overall assessment factor (AF):
- 2
- Dose descriptor:
- NOAEC
- AF for dose response relationship:
- 1
- Justification:
- default
- AF for differences in duration of exposure:
- 1
- Justification:
- no additional factor required
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- not applicable, human data
- AF for other interspecies differences:
- 1
- Justification:
- not applicable, human data
- AF for intraspecies differences:
- 2
- Justification:
- factor considered adequate based on experimental data
- AF for the quality of the whole database:
- 1
- Justification:
- default
- AF for remaining uncertainties:
- 1
- Justification:
- default
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 106 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- other: ECHA guidance with modification to interspecies factor
- Overall assessment factor (AF):
- 42
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 4 440 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- default
- AF for differences in duration of exposure:
- 6
- Justification:
- sub-acute to chronic factor
- AF for interspecies differences (allometric scaling):
- 1.4
- Justification:
- dog to human factor
- AF for other interspecies differences:
- 1
- Justification:
- no additional factor considered necessary
- AF for intraspecies differences:
- 5
- Justification:
- default
- AF for the quality of the whole database:
- 1
- Justification:
- default
- AF for remaining uncertainties:
- 1
- Justification:
- default
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
The context of this discussion is deriving an appropriate DNEL for the dermal route. Of the three components, monoethylene glycol (MEG, ethan-1,2-diol) is the most toxic and is the one with the most data and the one present in the highest concentration, as a conservative approach, the DNEL calculations are made on the assumption that the substance is 100% MEG.
The critical effects of Mono-ethylene glycol (MEG) after acute exposure are (in 3 subsequent stages) CNS toxicity, metabolic acidosis, and renal toxicity. Lethal effects in human adults (case reports from accidents, misuse, or suicidal attempts) occur from doses of 1600 mg/kg bw onwards, metabolic acidosis being strongly related to glycolic acid (GA) production and renal toxicity to oxalic acid (Hess et al., 2004). Repeated oral exposure to sub-lethal doses may lead to oxalate nephrosis (renal destruction by Ca-oxalate crystals) and is therefore considered to relevant for a STOT classification.
In terms of renal toxicity, rats appear to be more resistant than rabbits and less resistant than mice (NTP, 2004), however, also different strains of rats may show different sensitivities with more severity and more accumulation of oxalate in the kidneys of Wistar rats than Fischer rats (Cruzan et al., 2004). All subchronic and chronic oral studies in rats appear to converge in a NOAEL around 150 mg/kg bw and day (Corley et al., 2008).
In terms of developmental toxicity, mice (with critical doses from 500 mg/kg bw and day onwards) are more sensitive than rats (1000 mg/kg bw and day onwards) and rats as more sensitive than rabbits. In fact, rabbits appeared to be refractory and showed no developmental toxicity at oral doses of 1000 and 2000 mg/kg and day; these doses, in contrast to rats, led to pronounced maternal toxicity in the rebbits (Tyl et al., 1993). Rabbit pregnancies are not dependent on the inverted yolk sac placenta like rats and mice. There are reasons to assume that also humans, like rabbits, are either refractory or less prone to MEG-related developmental toxicity than rats and mice (Carney et al., 1994; NTP, 2004). For the onset of prenatal toxicity a saturation of glycolic acid oxidation appears to be critical.
A spontaneous formation and renal excretion of the MEG metabolites glycolic acid and oxalic acid has been noted in the human organism. This natural background can be set into perspective with biomonitoring results after occupational exposure. It has been shown that 4 hrs of MEG inhalation exposure to 25 mg/m3 or, equivalently, 6 hrs of dermal exposure to liquid MEG on a 66 cm2 skin surface led to an excretion rate of these metabolites at rates of 15 % and 2.2 %, respectively, above the naturally occuring levels (Upadhyay et al., 2008).
DNEL systemic inhalation: This is derived using route to route extrapolation to provide a starting point then appropriate assessment factors to produce the resultant DNEL. Note that this DNEL will be relevant when there is exposure to vapours.
DNEL acute inhalation: Inhalation exposure to MEG aerosols was shown to cause sensory irritation at concentrations higher than 140 mg/m3 in a human volunteer study. A concentration of 75 mg/m3 was well tolerated in a pilot experiment in four men. In a subsequent experiment with 20 volunteers 67 mg/m³ were confirmed as a NOAEC for a daily working-shift exposure over 1 week (Wills et al., 1974). Combined with a general assessment factor of 2 this NOAEC would result a DNEL of 35 mg/m3 for chronic local irritation. The internal dose obtained from an inhalation exposure under the conditions of the DNEL would be equivalent to an internal dose of 5 mg/kg bw which is approximatedly 30-fold below the oral NOAEL in rodents and, hence, the local DNEL should protect also from systemic toxicity. A more recent investigation (Upadhyay et al., loc. cit.) shows that under conditions of the German MAK value (25 mg/m3) the excretion of oxalic acid and glycolic acid is in the range of the natural background. Note that this DNEL is relevant when there is potential for exposure to aerosols.
DNEL long term dermal systemic: Explanation and justification for using dermal dog sub-acute study as a starting point: The key study is a set of two subsequent dermal 28 day studies in dogs (BASF, 1991) which were undertaken for the assessment of local and systemic toxicity of undiluted MEG including an ingredient, para-tert.-butylbenzoic acid (PTBBA; 1.42 % as sodium-salt) which is known for a potential of testicular toxicity. The undiluted formulation was spread on 30 % of the body surface. In a first study, dose levels of 0.5, 2 and 8 ml/kg bw and day were administered. In the top dose, severe nephrotoxicity (including lethalities) was observed and also some testicular toxicity. The latter was considered to be more a sequel of PTBBA than of renal toxicity. At 2 ml/kg bw and day (2220 mg/kg bw and day) there was an increase of urinary oxalate crystal formation which was considered as not adverse due to the absence of histological findings. In a second study, 2 and 4 ml/kg bw were employed; with this dose design a NOAEL of 4 ml /kg bw (4440 mg/kg bw) was identified. Again, an increase of urinary oxalate crystal formation could be detected but no adverse histopathological findings. The NOAEL of 4440 mg/kg bw is also supported by the results of a dermal developmental study in mice in which undiluted MEG at a dose level of 3500 mg/kg bw was considered a NOAEL for renal toxicity (Tyl et al., 1995). The large difference between the NOAELs from oral studies in rats and the dermal study in dogs may be explained, first of all, by the fact that the dermal resorption of MEG is much more limited than from oral uptake (Sun et al., 1995). Moreover, dogs and humans have a higher renal clearance rate for oxalic acid than rats (Corley et al., 2008). This may indicate that the allometric factor of 4 (between rats and humans) is well-based for acute toxicity but much less substantiated for (sub)chronic toxicity (oxalate nephrosis).
References
BASF, (1991)
Carney et al., Reprod.Toxicol. 8, 99 -113 (1994).
Corley et al., Toxicol.Appl.Pharmacol. 228, 165 -178 (2008).
Cruzan et al. Toxicol.Sci. 81, 502 -511 (2004).
Frantz et al., Xenobiotica 26, 1195 -1220 (1996).
Hess et al., Arch.Toxicol. 78, 671 -680 (2004).
Loden et al., Acta pharmacol. et toxicol. 58 (1986).
MAK-documentation (1991).
NTP, Reprod.Toxicol. 18, 457 -532 (2004).
Pottenger et al., Toxicol. Sci. 62, 10 -19 (2001).
Sun et al., (1995). - - ten Berge (2009).
Tyl et al., FAT 20, 402 -412 (1993)
Tyl et al., FAT 27, 155 -166 (1995).
Upadhyay et al., Toxicol. Lett. 178, 132 -140 (2008).
Wills et al., Clin.Toxicol. 7, 463 -476 (1974).-
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 35 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA guidance with modification to interspecies factor
- Overall assessment factor (AF):
- 20
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 700 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- There are no known uses of this multi-component substance in aerosol form, therefore only a DNEL for vapour inhalation is considered relevant. There is no inhalation study, so the NOAEL for oral dosing is used as a starting point with route to route extrapolation. The starting point is a NOAEL of 100mg/kgbw/day from a sub-chronic study in rats. Assuming a 70kg person and a inhaled volume of 10m3/8hr working day and 100% absorption, this equates to a NOAEC of 700mg/m3 (theoretical concentration).
- AF for dose response relationship:
- 1
- Justification:
- default
- AF for differences in duration of exposure:
- 2
- Justification:
- default for sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- default for inhalation study
- AF for other interspecies differences:
- 1
- Justification:
- no additional factor is required.
- AF for intraspecies differences:
- 10
- Justification:
- default
- AF for the quality of the whole database:
- 1
- Justification:
- default
- AF for remaining uncertainties:
- 1
- Justification:
- default
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 7 mg/m³
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
- DNEL derivation method:
- other: data from human volunteer studies
- Overall assessment factor (AF):
- 10
- Dose descriptor:
- NOAEC
- AF for dose response relationship:
- 1
- Justification:
- default
- AF for differences in duration of exposure:
- 1
- Justification:
- no additional factor required
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- not applicable, human data
- AF for other interspecies differences:
- 1
- Justification:
- not applicable, human data
- AF for intraspecies differences:
- 10
- Justification:
- default
- AF for the quality of the whole database:
- 1
- Justification:
- default
- AF for remaining uncertainties:
- 1
- Justification:
- default
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 53 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- other: ECHA guidance with modification to interspecies factor
- Overall assessment factor (AF):
- 84
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 4 440 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- default
- AF for differences in duration of exposure:
- 6
- Justification:
- sub-acute to chronic factor
- AF for interspecies differences (allometric scaling):
- 1.4
- Justification:
- dog to human factor
- AF for other interspecies differences:
- 1
- Justification:
- no additional factor considered necessary
- AF for intraspecies differences:
- 10
- Justification:
- default
- AF for the quality of the whole database:
- 1
- Justification:
- default
- AF for remaining uncertainties:
- 1
- Justification:
- default
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1.25 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: ECHA guidance with modification to interspecies factor
- Overall assessment factor (AF):
- 80
- Modified dose descriptor starting point:
- NOAEL
- AF for dose response relationship:
- 1
- Justification:
- default
- AF for differences in duration of exposure:
- 2
- Justification:
- default, sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- default, rat to human
- AF for other interspecies differences:
- 1
- Justification:
- no additional factor considered necessary
- AF for intraspecies differences:
- 10
- Justification:
- default
- AF for the quality of the whole database:
- 1
- Justification:
- default
- AF for remaining uncertainties:
- 1
- Justification:
- default
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 19 mg/kg bw/day
- Most sensitive endpoint:
- acute toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Modified dose descriptor starting point:
- LOAEL
- AF for dose response relationship:
- 5
- Justification:
- end point is lethality - other effects may occur at lower doses
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- not applicable, human data
- AF for other interspecies differences:
- 1
- Justification:
- not applicable, human data
- AF for intraspecies differences:
- 10
- Justification:
- default
- AF for the quality of the whole database:
- 1
- Justification:
- default
- AF for remaining uncertainties:
- 2
- Justification:
- overall additional factors for quality and accuracy of data used.
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
See discussion for workers. All DNELs for consumers are based on derivations as for workers with additional factors as shown.
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.