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EC number: 242-555-3 | CAS number: 18755-43-6
- 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:
- 1.96 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):
- 18
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 35.26 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- The starting point was corrected according to Figure R.8-3 in chapter R.8 in the ECHA guidance document (version 2.1, November 2012). It is assumed that the inhalation absorption in human is similar to the oral absorption in rat. NOAEL(oral, rat) = 20 mg/kg bw/day => NOAEC(corrected, inhalation) = NOAEL(oral, rat) x 1/(0.38 m3/kg bw/day) x 6.7 m3/10 m3 = 35.26 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- Default value (ECHA)
- AF for differences in duration of exposure:
- 6
- Justification:
- Default value (ECHA) for subacute to chronic exposure
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- rat versus human: According to table R.8-4 in chapter R.8 of the ECHA guidance document (version 2.1, November 2012) the AF of 4 is already included in the route to route extrapolation.
- AF for other interspecies differences:
- 1
- Justification:
- Data are also available for mice in a dominant lethal assay. No major systemic toxicity is observed at 500 mg/kg bw/day. Main effect in rats is alpha-2-microglobulin related nephropathy, a mechanism not relevant for humans. Consequently, it is likely that rodents are more sensitive than humans and no factor for "additional uncertainty" is applied.
- AF for intraspecies differences:
- 3
- Justification:
- The default value (ECHA) for workers is reduced because in rodents alpha-2-microglobulin accumulates in the kidney after oral dosing, an effect not relevant for human risk assessment. In addition a rapid and efficient excretion is anticipated based on the rodent data on dimethyl propylphosphonate and diethyl ethylphosphonate.
- AF for the quality of the whole database:
- 1
- Justification:
- A GLP guideline study is used.
- AF for remaining uncertainties:
- 1
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
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.56 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):
- 72
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 40 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- Based on the available physicochemical and toxicological data some dermal absorption might be assumed. Dermal absorption is likely to be lower than oral absorption based on the high water solubility and a low Log Kow = 0.5 only slightly above 0. For DNEL calculation dermal absorption is taken to be 2-fold lower than oral absorption. NOAEL(oral, rat) = 20 mg/kg bw/day => NOAEL(dermal, rat) = 2 x NOAEL(oral, rat) = 40 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- Default value (ECHA)
- AF for differences in duration of exposure:
- 6
- Justification:
- Default value (ECHA) for subacute to chronic exposure
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value (ECHA) for rat versus human
- AF for other interspecies differences:
- 1
- Justification:
- Data are also available for mice in a dominant lethal assay. No major systemic toxicity is observed at 500 mg/kg bw/day. Main effect in rats is alpha-2-microglobulin related nephropathy, a mechanism not relevant for humans. Consequently, it is likely that rodents are more sensitive than humans and no factor for "additional uncertainty" is applied.
- AF for intraspecies differences:
- 3
- Justification:
- The default value (ECHA) for workers is reduced because in rodents alpha-2-microglobulin accumulates in the kidney after oral dosing, an effect not relevant for human risk assessment. In addition a rapid and efficient excretion is anticipated based on the rodent data on dimethyl propylphosphonate and diethyl ethylphosphonate.
- AF for the quality of the whole database:
- 1
- Justification:
- A GLP guideline study is used.
- AF for remaining uncertainties:
- 1
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:
- low hazard (no threshold derived)
Additional information - workers
DNEL systemic (worker)
Basis for delineation of the DNELs systemic:
Short description of key study and/or point of departure
Title:
Levagard DMPP - subacute toxicity study in rats (4-week administration by gavage)
and
Levagard DMPP - subacute toxicity study in rats (4-week administration by gavage) Supplementary study
Administration period:
28 days
Doses:
0, 40, 200, or 1000 mg/kg bw/day or 0, 5, or 20 mg/kg bw/day (Suppl.) (males + females)
Local effects:
No local effects observed. Therefore no hazard identified
Systemic effects:
NOAEL 20 mg/kg bw/d
LOAEL: 40 mg/kg bw/d
Based on the following effects: alpha-2-microglobulin nephropathy and secondary kidney toxicity. The observed alpha-2-micro-globulin nephropathy is not regarded as relevant for humans, therefore a NOAEL of 20 mg/kg bw/d is stated.
Based on 2 oral subacute toxicity studies (T1074343 and T3074714) a NOAEL of 20 mg/kg bw/day is taken as a starting point. Observations in males and females at lower doses are considered to be related to alpha-2-microglobulin nephropathy and secondary kidney toxicity and consequently, not regarded as adverse effects in human risk assessment. The LOAEL is 40 mg/kg bw/day in these studies based on liver effects (hypertrophy) and clinical chemistry (decreased alkaline phosphatates) at this dose level.
Long-term toxicity – systemic effects (worker)
Assumption on respiratory absorption:
- Vapour pressure: 2.2E-06 hPa at 20°C (values below 5 hPa are regarded as low volatility according to the ECHA guidance document)
- Particle size: Physical state: Dimethyl propylphosphonate is a clear, colorless liquid
- Partition coefficient n-octanol/water (log value): Log Kow (Pow) = 0.5 (experimental)
- Water solubility: completely miscible with water (> 90% at 15°C); (according to the REACH guidance document passive diffusion might be limited, but dimethyl propylphosphonate might pass through aqueous pores based on a molecular weight below 200)
- Hydrolysis test: see Section 5.1.2 "Hydrolysis" (2011/0144/02)
- Acute inhalation toxicity: see Section 7.2.2 "Acute toxicity: inhalation" (T5083374)
Based on the data above respiratory absorption is assumed. Based on the physicochemical data and the oral toxicity data oral absorption is confirmed in a subacute toxicity study (although alpha-2-microglobulin nephropathy is not relevant for humans these systemic observations confirm oral absorption). In the course of this DNEL calculation respiratory absorption = oral absorption is regarded as a reasonable assumption.
Assumption on dermal absorption:
- Physical state: Dimethyl propylphosphonate is a clear, colorless liquid
- Molecular weight: 152.1287
- Water solubility: completely miscible with water (> 90% at 15°C).
- Partition coefficient n-octanol/water (log value): Log Kow (Pow) = 0.5 (experimental)
- Vapour pressure: 2.2E-06 hPa at 20°C
- Surface tension: no data available. Based on the structure, surface activity of the dimethyl propylphosphonate is not expected.
- Skin irritation: "slightly irritating"; no classification necessary
- Dermal toxicity: no data available
- Skin sensitization: not sensitizing in local lymph node assay (LLNA)
Based on the data above some dermal absorption might be assumed. Dermal absorption is likely to be lower than oral absorption based on the high water solubility and a low Log Kow (Pow) = 0.5 only slightly above 0. For DNEL calculation dermal absorption is taken to be 2-fold lower than oral absorption.
Reproductive Toxicity – systemic effects
Effects on fertility are observed in mice and rats and dimethyl propylphosphonate will be classified as Repr. 1B; H360.
In mice fertility parameter (e.g. dead implants) were affected in a dominant lethal mutation assay at 500 mg/kg bw/day. Based on comprehensive follow up investigations it was concluded that the observations are not due to genotoxic effects.
In a pilot reproduction/developmental toxicity screening test in rats (doses: 0, 20, 100 and 500 mg/kg bw/day) a low fertility index and pup survival was observed at 500 mg/kg bw/day.
Since effects on fertility are observed in rats and mice at 500 mg/kg bw/day, a dose 25-fold higher than the starting point for systemic toxicity, it is assumed that the systemic DNEL covers the endpoint reproduction.
DNEL local (worker)
Basis for delineation of the DNELs local (long and short term toxicity):
Irritation/corrosion:
In the skin irritation/corrosion study dimethyl propylphosphonate was 'slightly irritating to the skin' (exposure period: 4 hours).
Very slight, barely perceptible erythematous reactions were observed in all three animals. In one animal signs were evident only 1 hour post administration and in the other animals up to and at 72 hours and 14 days, respectively. Mean scores at 24, 48, and 73 hours: Erythema score = 0.66, edema score = 0.
In the eye irritation study dimethyl propylphosphonate was 'slightly irritating to the eye' (exposure period: 24 hours).
Reactions of the mucous membranes and cornea were observed in all three animals. The iris was also transiently affected in all three animals, but at different times. Discharge was observed in all three animals. Signs proved to be fully reversible within 21 days. Mean scores at 24, 48, and 72 hours: Cornea score = 1, iris score = 0.33, conjunctiva score = 1.55, chemosis score = 1.44)
No classification for skin irritation according GHS is justified. According GHS a classification as Eye Irrit. 2 (H319: Causes serious eye irritation) is required.
Sensitization:
A modified Local Lymph Node Assay (IMDS) was performed on 24 female NMRI mice (6 animals/test item group and 6 control animals) to determine if there is any specific (sensitizing) or non-specific (irritant) stimulating potential of the test item dimethyl propylphosphonate.
Compared to vehicle-treated animals, none of the parameters measured in the substance treated groups, i.e. cell counts and weights of the draining lymph nodes, ear weights and ear swelling, reached or exceeded the "positive levels" defined for this assay. These results show that there is no indication for a skin sensitizing effect after administration of a concentration up to and including 100% dimethyl propylphosphonate in this test system.
A classification is therefore not required.
Conclusion on local DNEL
There are no studies available to define a threshold for local toxicity after dermal application or inhalation. No Classification is required according to GHS. Therefore for local effects (dermal and inhalation) no hazard is identified.
For eye irritation, criteria for classification of dimethyl propylphosphonate with Eye irrit. 2; H319 according to GHS are fulfilled. According to ECHA guidance on information requirements and chemical safety assessment Part E: Risk characterization (version 2.0, November 2012) an allocation to the low hazard band is appropriate for compounds labeled with H319.
Long term DNEL local toxicity
Since dimethyl propylphosphonate is only slightly irritating in an in vivo irritation assay on the skin and on the eye and not sensitizing in LLNA, no local DNEL will be calculated. It is anticipated that the systemic DNEL covers the slight local effects.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.58 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):
- 30
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 17.39 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- The starting point was corrected according to Figure R.8-3 in chapter R.8 in the ECHA guidance document (version 2.1, November 2012). It is assumed that the inhalation absorption in human is similar to the oral absorption in rat. NOAEL(oral, rat) = 20 mg/kg bw/day => NOAEC(corrected, inhalation) = NOAEL(oral, rat) x 1/(1.15 m3/kg bw/day) = 17.39 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- Default value (ECHA)
- AF for differences in duration of exposure:
- 6
- Justification:
- Default value (ECHA) for subacute to chronic exposure
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- rat versus human: According to table R.8-4 in chapter R.8 of the ECHA guidance document (version 2.1, November 2012) the AF of 4 is already included in the route to route extrapolation.
- AF for other interspecies differences:
- 1
- Justification:
- Data are also available for mice in a dominant lethal assay. No major systemic toxicity is observed at 500 mg/kg bw/day. Main effect in rats is alpha-2-microglobulin related nephropathy, a mechanism not relevant for humans. Consequently, it is likely that rodents are more sensitive than humans and no factor for "additional uncertainty" is applied.
- AF for intraspecies differences:
- 5
- Justification:
- The default value (ECHA) for general population is reduced because in rodents alpha-2-microglobulin accumulates in the kidney after oral dosing, an effect not relevant for human risk assessment. In addition a rapid and efficient excretion is anticipated based on the rodent data on dimethyl propylphosphonate and diethyl ethylphosphonate
- AF for the quality of the whole database:
- 1
- Justification:
- A GLP guideline study is used.
- AF for remaining uncertainties:
- 1
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:
- DNEL (Derived No Effect Level)
- Value:
- 0.33 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):
- 120
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 40 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- Based on the available physicochemical and toxicological data some dermal absorption might be assumed. Dermal absorption is likely to be lower than oral absorption based on the high water solubility and a low Log Kow = 0.5 only slightly above 0. For DNEL calculation dermal absorption is taken to be 2-fold lower than oral absorption. NOAEL(oral, rat) = 20 mg/kg bw/day => NOAEL(dermal, rat) = 2 x NOAEL(oral, rat) = 40 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- Default value (ECHA)
- AF for differences in duration of exposure:
- 6
- Justification:
- Default value (ECHA) for subacute to chronic exposure
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value (ECHA) for rat versus human
- AF for other interspecies differences:
- 1
- Justification:
- Data are also available for mice in a dominant lethal assay. No major systemic toxicity is observed at 500 mg/kg bw/day. Main effect in rats is alpha-2-microglobulin related nephropathy, a mechanism not relevant for humans. Consequently, it is likely that rodents are more sensitive than humans and no factor for "additional uncertainty" is applied.
- AF for intraspecies differences:
- 5
- Justification:
- The default value (ECHA) for general population is reduced because in rodents alpha-2-microglobulin accumulates in the kidney after oral dosing, an effect not relevant for human risk assessment. In addition a rapid and efficient excretion is anticipated based on the rodent data on dimethyl propylphosphonate and diethyl ethylphosphonate.
- AF for the quality of the whole database:
- 1
- Justification:
- A GLP guideline study is used.
- AF for remaining uncertainties:
- 1
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:
- 0.16 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):
- 120
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 20 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- not applicable
- AF for dose response relationship:
- 1
- Justification:
- Default value (ECHA)
- AF for differences in duration of exposure:
- 6
- Justification:
- Default value (ECHA) for subacute to chronic exposure
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default value (ECHA) for rat versus human
- AF for other interspecies differences:
- 1
- Justification:
- Data are also available for mice in a dominant lethal assay. No major systemic toxicity is observed at 500 mg/kg bw/day. Main effect in rats is alpha-2-microglobulin related nephropathy, a mechanism not relevant for humans. Consequently, it is likely that rodents are more sensitive than humans and no factor for "additional uncertainty" is applied.
- AF for intraspecies differences:
- 5
- Justification:
- The default value (ECHA) for general population is reduced because in rodents alpha-2-microglobulin accumulates in the kidney after oral dosing, an effect not relevant for human risk assessment. In addition a rapid and efficient excretion is anticipated based on the rodent data on dimethyl propylphosphonate and diethyl ethylphosphonate.
- AF for the quality of the whole database:
- 1
- Justification:
- A GLP guideline study is used.
- AF for remaining uncertainties:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - General Population
DNELs (general population)
Basis for delineation of the DNELs systemic:
Short description of key study and/or point of departure
Title:
Levagard DMPP - subacute toxicity study in rats (4-week administration by gavage)
and
Levagard DMPP - subacute toxicity study in rats (4-week administration by gavage) Supplementary study
Administration period:
28 days
Doses:
0, 40, 200, or 1000 mg/kg bw/day or 0, 5, or 20 mg/kg bw/day (Suppl.) (males + females)
Local effects:
No local effects observed. Therefore no hazard identified
Systemic effects:
NOAEL 20 mg/kg bw/d
LOAEL: 40 mg/kg bw/d
Based on the following effects: alpha-2-microglobulin nephropathy and secondary kidney toxicity. The observed alpha-2-micro-globulin nephropathy is not regarded as relevant for humans, therefore a NOAEL of 20 mg/kg bw/d is stated.
Based on 2 oral subacute toxicity studies (T1074343 and T3074714) a NOAEL of 20 mg/kg bw/day is taken as a starting point. Observations in males and females at lower doses are considered to be related to alpha-2-microglobulin nephropathy and secondary kidney toxicity and consequently, not regarded as adverse effects in human risk assessment. The LOAEL is 40 mg/kg bw/day in these studies based on liver effects (hypertrophy) and clinical chemistry (decreased alkaline phosphatates) at this dose level.
Long-term toxicity – systemic effects (general population)
Assumption on respiratory absorption:
- Vapour pressure: 2.2E-06 hPa at 20°C (values below 5 hPa are regarded as low volatility according to the ECHA guidance document)
- Particle size: Physical state: Dimethyl propylphosphonate is a clear, colorless liquid
- Partition coefficient n-octanol/water (log value): Log Kow (Pow) = 0.5 (experimental)
- Water solubility: completely miscible with water (> 90% at 15°C); (according to the REACH guidance document passive diffusion might be limited, but dimethyl propylphosphonate might pass through aqueous pores based on a molecular weight below 200)
- Hydrolysis test: see Section 5.1.2 "Hydrolysis" (2011/0144/02)
- Acute inhalation toxicity: see Section 7.2.2 "Acute toxicity: inhalation" (T5083374)
Based on the data above respiratory absorption is assumed. Based on the physicochemical data and the oral toxicity data oral absorption is confirmed in a subacute toxicity study (although alpha-2-microglobulin nephropathy is not relevant for humans these systemic observations confirm oral absorption). In the course of this DNEL calculation respiratory absorption = oral absorption is regarded as a reasonable assumption.
Assumption on dermal absorption:
- Physical state: Dimethyl propylphosphonate is a clear, colorless liquid
- Molecular weight: 152.1287
- Water solubility: completely miscible with water (> 90% at 15°C).
- Partition coefficient n-octanol/water (log value): Log Kow (Pow) = 0.5 (experimental)
- Vapour pressure: 2.2E-06 hPa at 20°C
- Surface tension: no data available. Based on the structure, surface activity of the dimethyl propylphosphonate is not expected.
- Skin irritation: "slightly irritating"; no classification necessary
- Dermal toxicity: no data available
- Skin sensitization: not sensitizing in local lymph node assay (LLNA)
Based on the data above some dermal absorption might be assumed. Dermal absorption is likely to be lower than oral absorption based on the high water solubility and a low Log Kow (Pow) = 0.5 only slightly above 0. For DNEL calculation dermal absorption is taken to be 2-fold lower than oral absorption.
Reproductive Toxicity – systemic effects (general population)
Effects on fertility are observed in mice and rats and dimethyl propylphosphonate will be classified as Repr. 1B; H360.
In mice fertility parameter (e.g. dead implants) were affected in a dominant lethal mutation assay (T0058232) at 500 mg/kg bw/day. Based on comprehensive follow up investigations it was concluded that the observations are not due to genotoxic effects.
In a pilot reproduction/developmental toxicity screening test (T0083513) in rats a low fertility index and pup survival was observed at 500 mg/kg bw/day.
Since effects on fertility are observed in rats and mice at 500 mg/kg bw/day, a dose 25-fold higher than the starting point for systemic toxicity, it is assumed that the systemic DNEL covers the endpoint reproduction.
DNEL local (general population)
Basis for delineation of the DNELs local (long and short term toxicity):
Irritation/corrosion:
In the skin irritation/corrosion study dimethyl propylphosphonate was 'slightly irritating to the skin' (exposure period: 4 hours).
Very slight, barely perceptible erythematous reactions were observed in all three animals. In one animal signs were evident only 1 hour post administration and in the other animals up to and at 72 hours and 14 days, respectively. Mean scores at 24, 48, and 73 hours: Erythema score = 0.66, edema score = 0.
In the eye irritation study dimethyl propylphosphonate was 'slightly irritating to the eye' (exposure period: 24 hours).
Reactions of the mucous membranes and cornea were observed in all three animals. The iris was also transiently affected in all three animals, but at different times. Discharge was observed in all three animals. Signs proved to be fully reversible within 21 days. Mean scores at 24, 48, and 72 hours: Cornea score = 1, iris score = 0.33, conjunctiva score = 1.55, chemosis score = 1.44).
No classification for skin irritation according to GHS is justified. According GHS a classification as Eye Irrit. 2 (H319: Causes serious eye irritation) is required.
Sensitization:
A modified Local Lymph Node Assay (IMDS) was performed on 24 female NMRI mice (6 animals/test item group and 6 control animals) to determine if there is any specific (sensitizing) or non-specific (irritant) stimulating potential of the test item dimethyl propylphosphonate.
Compared to vehicle-treated animals, none of the parameters measured in the substance treated groups, i.e. cell counts and weights of the draining lymph nodes, ear weights and ear swelling, reached or exceeded the "positive levels" defined for this assay. These results show that there is no indication for a skin sensitizing effect after administration of a concentration up to and including 100% dimethyl propylphosphonate in this test system.
A classification is therefore not required.
Conclusion on local DNEL
There are no studies available to define a threshold for local toxicity after dermal application or inhalation. No Classification is required according to GHS. Therefore for local effects (dermal and inhalation) no hazard is identified.
For eye irritation, criteria for classification of dimethyl propylphosphonate with Eye irrit. 2; H319 according to GHS are fulfilled. According to ECHA guidance on information requirements and chemical safety assessment Part E: Risk characterization (version 2.0, November 2012) an allocation to the low hazard band is appropriate for compounds labeled with H319.
Long term DNEL local toxicity
Since dimethyl propylphosphonate is only slightly irritating in an in vivo irritation assay on the skin and on the eye and not sensitizing in LLNA, no local DNEL will be calculated. It is anticipated that the systemic DNEL covers the slight local effects.
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.