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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 201-126-0 | CAS number: 78-59-1
- 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
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:
- 11 mg/m³
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 22 mg/m³
DNEL related information
- DNEL extrapolated from long term DNEL
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 11 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 22 mg/m³
- Most sensitive endpoint:
- irritation (respiratory tract)
DNEL related information
- DNEL extrapolated from long term DNEL
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 13 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 300 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Converting the oral NOAEL rat into a dermal NOAEL is necessary to derive the correct starting point for the dermal route for which no study was carried out.
Conversion of an rat NOAELoral; rep. dosefrom OECD 443 rat oral reproductive toxicity study into an corrected NOAELderm; rep. dose (derived from example B.5; Appendix R 8-2 of TGD “Chapter R.8: Characterisation of dose [concentration]-response for human health”):
For worker:
assumptions:
- absorptionoral-rat= 100% (see Ad 2 of chapter R 8.4.2 of TGD)
- substance-specific data on dermal absorption for isophorone are available (see chapter 7.1.2 of IUCLID): In an in-vitro dermal absorption study with human skin disks the total amount absorbed was less than 5% even after exposure for 24 hours.
- Absorptiondermal-human= 5%
corrected NOAELderm; rep.dose= rat NOAELoral; rep. dose* (ABSoral-rat/ ABSderm-human)
= 65 mg/kg bw day * (100% / 5%)
= 1300 mg/kg bw day
- AF for dose response relationship:
- 1
- Justification:
- Starting point for the DNEL calculation is a NOAEL. Thus standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov. 2012).
- AF for differences in duration of exposure:
- 2
- Justification:
- A assessment factor 2 is suggested by the ECHA TGD for exposure duration from subchronic to chronic (see section R 8.4.3.1, Table R.8-5) (ECHA, Nov. 2012).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- An allometric scaling factor of 4 is suggested by the ECHA TGD (see section 8.4.3.1 of TGD; ECHA, Nov. 2012) for interspecies differences.
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor of 2.5 is suggested by the ECHA TGD (ECHA, Nov. 2012) for remaining interspecies differences.
- AF for intraspecies differences:
- 5
- Justification:
- For intraspecies variability, the default assessment factor for worker for systemic effects is 5 (ECHA, Nov. 2012).
- AF for the quality of the whole database:
- 1
- Justification:
- Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov. 2012).
- AF for remaining uncertainties:
- 1
- Justification:
- No further assessment factors are considered necessary.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 52 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- DNEL extrapolated from long term DNEL
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:
- low hazard (no threshold derived)
Additional information - workers
Inhalatory exposure
For workers in industrial and professional settings, which are exposed via inhalation, DNELs for acute and long-term inhalation effects of isophorone have to be derived. In addition, the eye and respiratory irritation potential of isophorone have to be assessed.
Regarding to ECHA Guidance, Chapter R.8, Appendix R.8 -13 in cases where toxicological information and evaluations of health effects used for setting a national OEL are documented and available, this may be used and taken into account in deriving the DNEL.
The current legally binding German occupational exposure limit (TRGS 900) is 11 mg/m3 (2 ppm) (Technical Rule for Hazardous Substances 900, German Federal Ministry of Labour and Social Affairs).
This value covers the repeated and acute inhalation toxicity, the irritation potential, and the carcinogenicity of isophorone (isophorone is not a genotoxic carcinogen), as the local effects at the eyes and the respiratory tract are the most sensitive effects.
On the basis of following data a ceiling limit of 2 ppm for isophorone is recommended. These data are well documented and available, they are valid and acceptable for assessment. In the new inhalation OECD 414 study with Fischer F344 rats no adverse effects were observed for maternal toxicity up to the highest dose of 151 ppm.
Effects on humans
Acute
Groups of 11 or 12 subjects exposed for a few minutes to atmospheric isophorone concentrations of 40, 85, 200 and 400 ppm experienced irritation of the eyes, nose and throat (Smyth and Seaton, 1940; see chapter 7.10.5 in IUCLID). A few complaints of nausea, headache, dizziness, faintness, inebriation and a feeling of suffocation occurred at concentrations of 200 and 400 ppm. The symptoms of irritation and narcosis were said to be less intensive following exposure to atmospheres containing 40 to 85 ppm.
Subchronic
Complaints of faitigue and malaise were reported among workers exposed for 1 month to atmospheres containing 28.5 to 48 mg isophorone/m3 (5 to 8 ppm) isophorone (Ware, 1973; see chapter 7.10.5 in IUCLID). No further complaints were received following a reduction of the concentration to between 5.7 and 23 mg/m3 (1 and 4 ppm). On the basis of these data the American Conference of Governmental Industrial Hygienists (ACGIH) recommended a ceiling limit of 5 ppm for isophorone.
Eye and respiratory irritation
Smyth and seaton (1940) reported eye, nose and throat irritation following exposure to isophorone levels of 40, 85, 200 and 400 ppm for a few minutes. At 40 and 85 ppm the initial irritation did not persist throughout the exposure.
Silverman et al. (1946; see chapter 7.10.5. in IUCLID) estimated the sensory threshold of a number of ketones including isophorone. An average of 12 subjects of both sexes were used for each solvent exposure. The time of exposure was 15 minutes. Irritation of the eyes, nose and throat was experienced at 25 ppm isophorone. 40 % of the exposed subjects objected isophorone odor at a concentration of 58 mg/m3 (10 ppm), and this concentration was judged to be the highest tolerable air level for 8 hour exposure.
Effects on animals
In a study with 6 weeks (8 hours/day, 5 days/week) duration, at doses >= 287 mg/m3(50 ppm) congested kidneys, dilated Bowman´s capsules and lung changes (irritation, congestion) were found in rats and guinea pigs (Smyth et al., 1942; see chapter 7.5.3 in IUCLID). At doses of 25 ppm (144 mg/m3) isophorone no effects were observed.
In rats exposed for 4 weeks (6 hours/day, 5 days/week) to 208 mg isophorone/m3reduced body weights and decreased liver weights in males and changes in heamatological parameters in females were found (NOAEC (rat, 28 days) < 208 mg/m3 or < 36 ppm) (Exxon, 1968; see chapter 7.5.3 in IUCLID).
Therefore, concerning the irritant effects in humans and the observed effects in animals studies (eye and nose irritation; blood and liver changes) an occupational exposure limit of 11 mg/m3 (2 ppm) was derived. This value is in line with other DNEL values derived from acute and long-term inhalation studies (calculations see below) and with the eye and respiratory irritation potential of isophorone, leading to a
Worker-DNEL long-term for inhalation route - local effects = 11 mg/m3
and a
Worker-DNEL long-term for inhalation route - systemic effects = 11 mg/m3
Calculations for inhalation exposure
(1) Conversion of an rat LOAECinhalatory; rep. dosefrom 28 day rat inhalativ repeated dose toxicity study into an corrected LOAECinhalatory; rep. dose (derived from figure R.8-2; Chapter R 8.4.2 of TGD “Chapter R.8: Characterisation of dose [concentration]-response for human health”):
For workers:
assumptions:
8h exposure/day
Inhalation absorption rat = inhalation absorption human
corrected LOAECinhalatory; rep.dose = rat LOAECinhalatory; rep. dose* ((6 h/d) / (8 h/d)) * (6.7 m3(8h) / 10 m3(8h))
= 208 mg/m3* 0.75 * 0.67
= 104.52 mg/m3
Selected assessment factors (according to Table R 8-6 of the TGD):
- Interspecies: factor for allometric scaling (systemic) 1*
- Interspecies: remaining differences (systemic) 2.5
- Intraspecies (worker, systemic) 5**
- Exposure duration (systemic; subacute to chronic) 1***
- Dose-response (systemic) 3****
- Quality of the database (systemic; overall) 1*****
overall Assessment Factor (overall AF) 37.5
* According to ECHA TGD an allometric scaling factor is not applicable when setting an inhalation DNEL based on an inhalation animal study (see Appendix R.8-2), therefore AF 1 is chosen.
** For intraspecies variability, the default assessment factor for workers is 5.
*** The assessment factor suggested by the ECHA TGD for exposure duration from subacute to chronic should be 6, but extrapolation factors for differences in duration of exposure are not always reasonable. In the depicted case the lowest relevant LOAEC-value = 208 mg/m3, derived from a subacute inhalation study in rats. All other observed LOAEC-values derived from subchronic and chronic inhalation studies were determined to be > 208 mg/m3. (LOAECchronic, rat and rabbit = 1436 mg/m3; LOAECsubchronic, rat = 2873 mg/m3; NOAECfertility, rat > 2873 mg/m3; NOAECteratogen, rat> 664 mg/m3)
On this basis it is not expected that a longer duration of the study would change the outcome and an AF of 1 is warranted.
**** Starting point is a LOAEC. Thus standard assessment factor 3 is used as described in chapter R 8.4.3.1 of TGD
***** Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD
(2) Conversion of an rat NOAELinhalatory; fertilityfrom fertility toxicity study into an corrected NOAECinhalatory; fertility(derived from figure R.8-2; Chapter R 8.4.2 of TGD “Chapter R.8: Characterisation of dose [concentration]-response for human health”):
For workers:
assumptions:
8h exposure/d
Inhalation absorption rat = inhalation absorption human
corrected NOAECinhalatory;fertility;male/female= rat NOAECinhalatory; fertility;male/female * ((6 h/d) / (8 h/d)) * (6.7 m3(8h) /10 m3 (8h)) = > 2873 mg/m3* 0.75 * 0.67 = > 1444 mg/m3
Selected assessment factors (according to Table R 8-6 of the TGD):
- Interspecies: factor for allometric scaling (systemic) 1*
- Interspecies: remaining differences (systemic) 2.5
- Intraspecies (systemic) 5**
- Exposure duration (systemic; subchronic to chronic) 2
- Dose-response (systemic) 1***
- Quality of the database (systemic; overall) 1****
overall Assessment Factor (overall AF) 25
* According to ECHA TGD an allometric scaling factor is not applicable when setting an inhalation DNEL based on an inhalation animal study (see Appendix R.8-2), therefore AF 1 is chosen.
**For intraspecies variability, the default assessment factor for workers is 5.
*** Starting point is a NOAEL. Thus standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD
**** Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD
(3) Conversion of an rat NOAECinhalatory; developfrom developmental toxicity study into an corrected NOAECinhalatory; develop(derived from figure R.8-2; Chapter R 8.4.2 of TGD “Chapter R.8: Characterisation of dose [concentration]-response for human health”):
For workers:
assumptions:
8h exposure/d
Inhalation absorption rat = inhalation absorption human
corrected NOAECinhalatory;develop= rat NOAECinhalatory; develop*((6 h/d) / (8 h/d)) * (6.7 m3(8h) / 10 m3(8h))
= > 664 mg/m3* 0.75 * 0.67
= > 334 mg/m3
Selected assessment factors (according to Table R 8-6 of the TGD):
- Interspecies: factor for allometric scaling (systemic) 1*
- Interspecies: remaining differences (systemic) 2.5
- Intraspecies (systemic) 10**
- Exposure duration (systemic; subchronic to chronic) 1
- Dose-response (systemic) 1***
- Quality of the database (systemic; overall) 1****
overall Assessment Factor (overall AF) 25
* According to ECHA TGD an allometric scaling factor is not applicable when setting an inhalation DNEL based on an inhalation animal study (see Appendix R.8-2), therefore AF 1 is chosen.
**According to TGD Appendix R 8-12: Pregnant women have to be considered as a more vulnerable
population. When deciding on assessment factors for the DNELdevelopcalculation the developing
offspring should be the focus of attention. Therefore intraspecies factor of 5 for workers is
enhanced 2-fold resulting in an assessment factor of 10.
*** Starting point is a NOAEC. Thus standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD
**** Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD
***** The exposure and the scope of the animal OECD 414 study is limited to the prenatal stadium and thus it has to be considered to be a chronic exposure for the unborn foetus, which is the focus of attention in this study and regarding the derivation of the DNELdevelop. Thus extrapolation of duration of exposure is not needed and assessment factor is set on 1.
(4) Conversion of an rat LOAELoral; cancer from carcinogenicity study into an corrected LOAECinhalatory; cancer(derived from figure R.8-3; Chapter R 8.4.2 of TGD “Chapter R.8” and example B 3 of Appendix R 8-2 of TGD)
For workers:
assumptions:
- 8h exposure/d
- (ABSoral-rat/ ABSinh-human) = 0.5 (according to Ad 2 of Chapter 8.4.2 of TGD)
corrected LOAECinhalatory; cancer= rat LOAELoral; cancer * (1 / sRVrat) * (ABSoral-rat/ ABSinh-human) *
(sRVhuman/wRV)
= 500 mg/kg bw d * (1/ 0.38 m3/kg bw d) * 0.5 * (6.7 m3 (8h) / 10 m3 (8h))
= 440 mg/m3
Selected assessment factors (according to Table R 8-6 of the TGD):
- Interspecies: factor for allometric scaling (systemic) 1*
- Interspecies: remaining differences (systemic) 2.5
- Intraspecies (systemic) 5**
- Exposure duration (systemic; chronic) 1
- Dose-response (systemic) 3***
- Quality of the database (systemic; overall) 1****
overall Assessment Factor (overall AF) 37.5
* see example B 3 of Appendix R 8-2 of TGD
**For intraspecies variability, the default assessment factor for workers is 5.
*** Starting point is a LOAEC. Thus standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD
**** Because of good/standard quality of the database the standard assessment factor 3 is used as described in chapter R 8.4.3.1 of TGD
(5) Conversion of an rat LOAECinhalatory; rep. dosefrom 18 months rat inhalativ repeated dose toxicity study into an corrected LOAECinhalatory; rep. dose (local effects) (derived from figure R.8-2; Chapter R 8.4.2 of TGD “Chapter R.8: Characterisation of dose [concentration]-response for human health”):
For workers:
assumptions:
8h exposure/day
Inhalation absorption rat = inhalation absorption human
corrected LOAECinhalatory; rep.dose = rat LOAECinhalatory; rep. dose* ((6 h/d) / (8 h/d)) * (6.7 m3(8h) / 10 m3(8h))
= 1436 mg/m3* 0.75 * 0.67
= 721.6 mg/m3
Selected assessment factors (according to Table R 8-6 of the TGD):
- Interspecies: factor for allometric scaling (local) 1*
- Interspecies: remaining differences (local) 2.5
- Intraspecies (worker, local) 5**
- Exposure duration (local; chronic) 1
- Dose-response (local) 3***
- Quality of the database (local; overall) 1****
overall Assessment Factor (overall AF) 37.5
* According to the ECHA TGD allometric scaling should not be applied for local effects on eyes, since these effects are independent of the basal metabolic rate, therefore AF 1 is chosen.
** For intraspecies variability, the default assessment factor for workers is 5.
*** Starting point is a LOAEC. Thus standard assessment factor 3 is used as described in chapter R8.4.3.1 of TGD.
**** Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD.
(6) Derivation of a DNELshort-term extrapolated from the DNEL long-term (according to ECHA Guidance, Chapter R.8., Appendix R. 8 -8, Box 6)
According to the German rule for OELs (Technical Rule for Hazardous Substances 900, German Federal Ministry of Labour and Social Affairs, 2006/2009) for short-term ceiling concentrations an exposure limit could be established by multiplication of an occupational exposure limit (Arbeitsplatzgrenzwert) to an exceeding factor (Überschreitungsfaktor), which is set per default 1, but can be adjusted up to the value of 8 in maximum. For isophorone an factor of 2 is applied, as even a short time exceeding up to 4 ppm (22 mg/m3) does not lead to local irritations that were only reported for higher concentrations.
Worker-DNELacute for inhalation route - local effects = 22 mg/m3
Worker-DNELacutefor inhalation route - systemic effects = 22 mg/m3
Dermal exposure
Additionally, for workers in industrial and professional settings, which are exposed via dermal contact, DNELs for systemic, acute and long-term dermal effects of isophorone have to be derived. No indications of local toxicity were found within several long- and short-term toxicity studies.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.7 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 75
- Modified dose descriptor starting point:
- LOAEC
- Value:
- 52 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Conversion of an rat LOAECinhalatory; rep. dosefrom 28 day rat inhalativ repeated dose toxicity study into an corrected LOAECinhalatory; rep. dose (derived from figure R.8-2; Chapter R 8.4.2 of TGD “Chapter R.8: Characterisation of dose [concentration]-response for human health”):
For general population:
assumptions:
24 h exposure/day
Inhalation absorption rat = inhalation absorption human
corrected LOAECinhalatory; rep.dose = rat LOAECinhalatory; rep. dose* ((6 h/d) / (24 h/d))
= 208 mg/m3* 0.25
= 52 mg/m3
- AF for dose response relationship:
- 3
- Justification:
- Starting point is a LOAEC. Thus standard assessment factor 3 is used as described in chapter R 8.4.3.1 of ECHA TGD (ECHA, Nov. 2012).
- AF for differences in duration of exposure:
- 1
- Justification:
- The assessment factor suggested by the ECHA TGD for exposure duration from subacute to chronic should be 6, but extrapolation factors for differences in duration of exposure are not always reasonable. In the depicted case the lowest relevant LOAEC value is 208 mg/m3, derived from a subacute inhalation study in rats. All other observed LOAEC values derived from subchronic and chronic inhalation studies were determined to be > 208 mg/m3. (LOAEC chronic, rat and rabbit = 1436 mg/m3; LOAEC subchronic, rat = 2873 mg/m3; NOAEC fertility, rat > 2873 mg/m3; NOAEC teratogen, rat > 664 mg/m3) On this basis it is not expected that a longer duration of the study would change the outcome and an AF of 1 is warranted.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- According to ECHA TGD (ECHA, Nov. 2012) an allometric scaling factor is not applicable when setting an inhalation DNEL based on an inhalation animal study (see Appendix R.8-2), therefore AF 1 is chosen.
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor of 2.5 is suggested by the ECHA TGD (ECHA, Nov. 2012) for remaining interspecies differences
- AF for intraspecies differences:
- 10
- Justification:
- For intraspecies variability, the default assessment factor for general population for systemic effects is 10 (ECHA, Nov. 2012).
- AF for the quality of the whole database:
- 1
- Justification:
- Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R 8.4.3.1 of ECHA TGD (ECHA, Nov. 2012).
- AF for remaining uncertainties:
- 1
- Justification:
- No further assessment factors are considered necessary.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.7 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL extrapolated from long term DNEL
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.7 mg/m³
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.7 mg/m³
DNEL related information
- DNEL extrapolated from long term DNEL
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
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:
- 0.325 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 200
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 65 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- No route-to-route-extrapolation needed
- AF for dose response relationship:
- 1
- Justification:
- Starting point for the DNEL calculation is a NOAEL. Thus standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov. 2012).
- AF for differences in duration of exposure:
- 2
- Justification:
- A assessment factor 2 is suggested by the ECHA TGD for exposure duration from subchronic to chronic (see section R 8.4.3.1, Table R.8-5) (ECHA, Nov. 2012).
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- An allometric scaling factor of 4 is suggested by the ECHA TGD (see section 8.4.3.1 of TGD; ECHA, Nov. 2012) for interspecies differences.
- AF for other interspecies differences:
- 2.5
- Justification:
- A factor of 2.5 is suggested by the ECHA TGD (ECHA, Nov. 2012) for remaining interspecies differences.
- AF for intraspecies differences:
- 10
- Justification:
- For intraspecies variability, the default assessment factor for the general population is 10 (ECHA, Nov. 2012).
- AF for the quality of the whole database:
- 1
- Justification:
- Because of good/standard quality of the database the standard assessment factor 1 is used as described in chapter R 8.4.3.1 of TGD (ECHA, Nov. 2012).
- AF for remaining uncertainties:
- 1
- Justification:
- No further assessment factors are considered necessary.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.325 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL extrapolated from long term DNEL
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
Isophorone is exclusively used as a solvent for resins, polymers and pesticides formulations. A direct use of this substance is not known. The exposure of consumers to isophorone via consumer productsis not given, because no consumer product is known to contain isophorone.
An exposure of the general population via the environment might occur through ingestion of foodstuff or drinking water or by absorbing the substance in air, that came in contact with isophorone via the use as solvent for agrochemicals. Bystanders and residents can also be exposed to the mixture containing isophorone during professional spraying in agrochemical use.
Therefore, an oral DNEL systemic, long-term and an inhalation DNEL(systemic and local), long-term for general population is derived.
Furthermore, a risk assessment for bystanders and residents for agrochemical uses is provided in this CSR (see section 9.7).
Nevertheless isophorone released to the environment would rapidly be degraded in water and photooxidants. Additionally, in view of low toxicity in experimental studies and low levels of exposure from environment sources, the risk to the general population appears to be minimal.
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.