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EC number: 245-740-7 | CAS number: 23564-05-8
- 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:
- 0.86 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 12.5
- Dose descriptor starting point:
- NOAEL
- Value:
- 8.8 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 10.9 mg/m³
- Explanation for the modification of the dose descriptor starting point:
Please refer to additional information.
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 1
- Justification:
- No time extrapolation factor is needed since a chronic toxicity study is available.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
- AF for other interspecies differences:
- 2.5
- Justification:
- Default AF for remaining differences.
- AF for intraspecies differences:
- 5
- Justification:
- The default value for the relatively homogenous group "worker" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8.4 mg/m³
- Most sensitive endpoint:
- acute toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Explanation for the modification of the dose descriptor starting point:
Please refer to additional information.
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- skin irritation/corrosion
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4.2 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Dermal
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 180
- Dose descriptor starting point:
- NOAEL
- Value:
- 1 000 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 750 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
Please refer to additional information.
- AF for dose response relationship:
- 1
- Justification:
- The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 6
- Justification:
- The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).
- AF for interspecies differences (allometric scaling):
- 2.4
- Justification:
- The default allometric scaling factor for the differences between rabbits and humans is used.
- AF for other interspecies differences:
- 2.5
- Justification:
- Default AF for other interspecies differences.
- AF for intraspecies differences:
- 5
- Justification:
- The default value for the relatively homogenous group "worker" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- The quality of the whole data base is considered to be sufficient and uncritical.
- AF for remaining uncertainties:
- 1
- Justification:
- The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
- Most sensitive endpoint:
- acute toxicity
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Acute/short term exposure
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
General
DNEL derivation for the test item is performed under consideration of the recommendations of ECHA, Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose-response for human health (Version: 2.1, November 2012).
Inhalation
Long term, systemic DNEL – exposure via inhalation (workers)
No repeated dose inhalation toxicity study with the target substance is available. Therefore, it will be necessary to obtain a long-term DNEL by route-to-route extrapolation:
A study according EPA OPP 83-5 (GLP) and similar to OECD TG 453 performed in rats is available and a 1-year oral administration study in dogs. The study according OECD TG 453 performed in rats was used as key study because of the chronic exposure duration compared to the 1-year dog study.
In males and females rats at dose levels of 1200 or 6000 ppm treatment-related effects were seen which included body weight depression, anemia, accelerated nephropathy, adrenal cortical lipidosis, hepatocellular hypertrophy with an associated increase in serum cholesterol and total protein, decreased T3/T4, increased TSH, and thyroid follicular hyperplasia. A treatment-related increase in organ weights of liver, thyroid and kidneys also occurred. Based upon body weight depression and mortality, the MTD was determined to be 1200 ppm for both sexes. At 6000 ppm, approximately 5 times the MTD, an increase in thyroid follicular cell adenomas was observed in the males. These adenomas were considered to be a secondary effect, related to the treatment-related changes in hormonal homeostasis of the pituitary-thyroid axis. The NOAEL was 200 ppm (8.8 and 10.2 mg/kg bw/day in male and female rats, respectively).
The substance is harmonized classified for Muta. 2 (H341) and is harmonized classified for carcinogenicity Cat.2 (H351). The experimental results suggest that for the mutagenicity of the test item an aneugenic mechanism is prevalent while clastogenicity is not demonstrated. The available in vivo studies in germ cells did not demonstrate any genotoxic effect.
According to the new Draft guidance on aneugenicity assessment (EFSA Scientific Committee (SC), 2020) TPM is a purely aneugenic substance and threshold setting is justified based on the underlying mode of action (please refer to attached statement).
If a substance is demonstrated to be an aneugen, it is assumed that its genotoxicity is thresholded, in contrast to non-thresholded genotoxicity. Both types of genotoxicity mechanisms trigger different ways to perform risk assessment (ECHA Endpoint specific guidance 7a, 2017). Therefore, a DNEL was derived and the NOAEL of 8.8 mg/kg bw/day was as PoD.
Step 1: PoD: NOAEL = 8.8 mg/kg bw/day
Step 2: Modification of PoD:
Standard respiratory volume, human (sRVhuman) for 8 hours: 6.7 m3
Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m3/kg bw
Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m3
Oral absorption of the rat/ inhalation absorption of humans (ABS oral-rat / ABS inh-human): 50%/100 % (default)
Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker
Corrected NOAEC (inhalation) for workers:
= 8.8 mg/kg bw/day x 0.5 x 1/0.38 m3/kg bw/day x (6.7 m3/10 m3) x 1.4
= 10.9 mg/m3
Step 3: Overall AF= 12.5
Intraspecies AF (worker): 5
Interspecies AF, remaining differences: 2.5
Dose response relationship AF: 1
Exposure duration AF: 1 (chronic study)
Whole database AF: 1
The toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
In conclusion,long term systemic inhalation DNEL, workers = 0.86 mg/m3
Acute, systemic DNEL- exposure via inhalation (workers)
Due to the acute inhalation toxicity observed for the test item (LC50=1700 mg/m3), the substance is considered to be classified for acute inhalation toxicity Cat.4 under Regulation (EC) No 1272/2008. In the ECHA Guidance it is stated that “[...] a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures.”
From an acute toxicity study a LC50 of 1700 mg/m3 was obtained. In this study sub-lethal effects have been reported for male and female animals at 500 mg/m3 (0.5 mg/L) after 4 h exposure (=240 min). This dose is used as PoD.
Time extrapolation using the modified Haber´s law: Cnx t = k; n=3 for extrapolation from long to short exposure times, C=0.5 mg/L, t=240 min
Cnx t = Cn’ x t’
0.53x 240 min = Cn‘ x 15 min
C‘ =
³√[(0.125*240)/15]
For a 15 min exposure time: C’=1.26 mg/L
Correction for differences in respiratory volumes between animals (usually at rest) and humans (light activity for worker): 0.67
1.26 mg/L x 0.67 = 0.84 mg/L
AF: 100 (default)
0.84/100
DNEL, short-term systemic inhalation = 8.4 mg/m3
Long term & acute, local DNEL- exposure via inhalation (workers)
The substance is not classified for skin/eye irritation and in conclusion local mucosal membrane damage of the respiratory membranes is not expected. Therefore, no DNEL was derived.
Dermal
Long term, systemic DNEL- exposure via dermal route (workers)
A subacute repeated dose dermal toxicity study with the target substance is available.
A study according to EPA 82-2 and similar to OECD TG 410 was conducted. New-Zealand White rabbits were treated with the substance at doses of 100, 300 and 1000 mg/kg bw/day. The NOAEL is considered to be 1000 mg/kg bw/day under the conditions of this study.
Step 1:PoD: NOAEL = 1000 mg/kg bw/day
Step 2:Modification into a correct starting point:
Correction for difference between human and experimental exposure conditions: 6 h per day/5 days vs. 8 h per day/5 days (=0.75)
Corrected NOAEL (dermal) for workers:
= 1000 mg/kg bw/day x 0.75
= 750 mg/kg bw/day
Step 3:Overall AF= 180
Interspecies AF, allometric scaling (rabbit to human): 2.4
Interspecies AF, remaining differences: 2.5
Intraspecies AF (worker): 5
Dose-response relationship AF: 1
Exposureduration AF: 6 (subacute to chronic)
In conclusion,long term systemic dermal DNEL, workers = 4.2 mg/kg bw/day
Acute, systemic DNEL- dermal exposure (workers)
According to ECHA Guidance on information requirements and chemical safety, Chapter R.8, Appendix R. 8-8, „a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified. The substance has low acute dermal toxicity with the LD50 of >2000 mg/kg. Therefore, the DNEL is not required.
Long term & acute, local DNEL- dermal exposure (workers)
According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterization, a qualitative risk characterization should be performed for this endpoint. This qualitative approach has to be implemented to deal with the skin sensitizing properties of the substance. As a result, a medium hazard is derived. In order to guarantee "adequately control of risks", it is necessary to stipulate risk management measures that prevent skin, eye and mucous membrane exposure.
Hazard to the eye-local effects (worker)
The test item is not classified for eye damage according to Regulation (EC) No 1272/2008 (CLP).
References
ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8:
Characterisation of dose [concentration]-response for human health. Version 2.1, November 2012
ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation, Version 3.0, May 2016
ECHA (2017).Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7a: Endpoint specific guidance, Version 6.0
SCC GmbH; 2020. Evaluation of the genotoxicity hazard of Thiophanate-methyl (TPM, CAS 23564-05-8) based on the Draft guidance on aneugenicity assessment (EFSA Scientific Committee (SC), 2020)
General Population - Hazard via inhalation 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
DNEL related information
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
- Most sensitive endpoint:
- acute toxicity
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:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
No hazard to the general population is expected since the substance is only formulated in plant protection products in EU and afterwards exported.
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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