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EC number: 200-806-4 | CAS number: 74-31-7
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

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:
- 1.41 mg/m³
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 5
- Dose descriptor starting point:
- NOAEL
- Value:
- 8 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 7.05 mg/m³
- Explanation for the modification of the dose descriptor starting point:
NOAEC corrected inhalative = 8 * (50/100) * (1/0.38) * (6.7/10) = 7.05 mg/m3
- AF for dose response relationship:
- 1
- Justification:
- Default assessment factor for NOAEL as starting point (ECHA Guidance, Chapter R.8, 2012)
- AF for differences in duration of exposure:
- 1
- Justification:
- The available information indicate that adverse effects of DPPD are restricted to pregnancy. In the OECD 421 study, the entire pregnancy period in the rat is covered, and therefore, an assessment factor for exposure duration is not considered necessary.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No allometric scaling has to be applied in case of oral to inhalation route to route extrapolation according to ECHA Guidance, Chapter R.8, 2012.
- AF for other interspecies differences:
- 1
- Justification:
- A mechanism of the prolonged gestation period caused by DPPD has been investigated in the literature:
Marois (Bull. Acad. Natl. Med;1982(3):581-95, 1998) found that a single application of PGF2α on the 21st day of gestation re-establishes the normal onset of parturition in rats that had previously been treated with DPPD from day 14 of gestation onwards. Fujita et al. (Experentia 38(12), 1472, 1982) found that DPPD inhibited the synthesis of PGE in rabbit kidney medulla slices. Yohko et al. (J. Pharm. PHarmacol, 1984, 36:195-197) that this inhibition could be reversed by addition of arachidonic acid.
These results indicate that prolongation of the gestation period of DPPD is mediated by an inhibition of PGF2α and/or PGE2.
PGF2α and PGE2 are known to be critical modulators of parturition in rats and mice by induction of luteolysis (PGF2α) and cervix ripening (PGE2), respectively, prior to birth. While the effects in mediated by PGE2 in this context are comparable in rats and humans, a significant interspecies difference exists regarding the influence of PGF2α: In humans and guinea pigs, luteolysis is not a key event to initiate parturition. Birth can begin without a prior decrease in progesterone levels. For mice and rats, this process is, however, critical (Welsh et al., J. PHysiol. 569.3(2005) 903-912).
In conclusion, human relevance of this mode of action can thus not be excluded: The DPPD effects mediated by interference with PGE2 may in principle also be relevant to humans; however, interference with PGF2α represents a second crucial modulator in rats, which is irrelevant in humans. It is therefore likely that the rat represents a quantitative and qualitative worst case compared to humans. Therefore, the default assessment factors (acc. to ECHA GD R8) have been modified into a substance specific assessment factor of 1 considering the intrinsic hazard properties of DPPD. - AF for intraspecies differences:
- 5
- Justification:
- A default factor of 5 for workers according to ECHA Guidance, Chapter R.8, 2012.
- AF for the quality of the whole database:
- 1
- Justification:
- GLP Guideline Study
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties.
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:
- 0.4 mg/kg bw/day
- Most sensitive endpoint:
- effect on fertility
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 20
- Dose descriptor starting point:
- NOAEL
- Value:
- 8 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 8 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
According to R8 ECHA 2012 in general, it can be assumed that dermal absorption will not be higher than oral absorption, and thus no default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation
- AF for dose response relationship:
- 1
- Justification:
- Default assessment factor for NOAEL as starting point (ECHA Guidance, Chapter R.8, 2012)
- AF for differences in duration of exposure:
- 1
- Justification:
- The available information indicate that adverse effects of DPPD are restricted to pregnancy. In the OECD 421 study, the entire pregnancy period in the rat is covered, and therefore, an assessment factor for exposure duration is not considered necessary.
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Default factor for allometric scaling according to ECHA Guidance, Chapter R.8, 2012
- AF for other interspecies differences:
- 1
- Justification:
- A mechanism of the prolonged gestation period caused by DPPD has been investigated in the literature:
Marois (Bull. Acad. Natl. Med;1982(3):581-95, 1998) found that a single application of PGF2α on the 21st day of gestation re-establishes the normal onset of parturition in rats that had previously been treated with DPPD from day 14 of gestation onwards. Fujita et al. (Experentia 38(12), 1472, 1982) found that DPPD inhibited the synthesis of PGE in rabbit kidney medulla slices. Yohko et al. (J. Pharm. PHarmacol, 1984, 36:195-197) that this inhibition could be reversed by addition of arachidonic acid.
These results indicate that prolongation of the gestation period of DPPD is mediated by an inhibition of PGF2α and/or PGE2.
PGF2α and PGE2 are known to be critical modulators of parturition in rats and mice by induction of luteolysis (PGF2α) and cervix ripening (PGE2), respectively, prior to birth. While the effects in mediated by PGE2 in this context are comparable in rats and humans, a significant interspecies difference exists regarding the influence of PGF2α: In humans and guinea pigs, luteolysis is not a key event to initiate parturition. Birth can begin without a prior decrease in progesterone levels. For mice and rats, this process is, however, critical (Welsh et al., J. PHysiol. 569.3(2005) 903-912).
In conclusion, human relevance of this mode of action can thus not be excluded: The DPPD effects mediated by interference with PGE2 may in principle also be relevant to humans; however, interference with PGF2α represents a second crucial modulator in rats, which is irrelevant in humans. It is therefore likely that the rat represents a quantitative and qualitative worst case compared to humans. Therefore, the default assessment factors (acc. to ECHA GD R8) have been modified into a substance specific assessment factor of 1 considering the intrinsic hazard properties of DPPD. - AF for intraspecies differences:
- 5
- Justification:
- A default factor of 5 for workers according to ECHA Guidance, Chapter R.8, 2012.
- AF for the quality of the whole database:
- 1
- Justification:
- GLP guideline study
- AF for remaining uncertainties:
- 1
- Justification:
- No remaining uncertainties
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
Several repeated dose studies are available based on which a DNEL could be derived:
In a 28-day study in rats according to OECD 407 (Matsumoto et al., 2013), DPPD was administered via gavage at 100, 300 and 1000 mg/kg bw/d. The only relevant findings were significantly reduced food consumpation during week 4 in the males of the 300 mg/k group and during weeks 3 and 4 in the males of the 1000 mg/kg group. However, this was not accompanied by any effects on body weight or body weight gain. In addition, total bilirubin was significantly increased in the males of all treatment groups at the end of the treatment period. This increase had reversed at the end of the recovery period. No histopathological correlates were found in the liver, and bilirubin or urobilirubinogen levels in urine did not increase. Therefore, the NOAEL in this study is 1000 mg/kg bw/d.
In a long-term feeding study, Hasegawa et al. (1989) treated rats with DPPD via the diet (0.5 or 2% of DPPD) for 104 weeks. A LOAEL of 0.5% was observed in this study (corresponding to 194 mg/kg for males and to to 259 mg/kg for females), based on haematological alterations (in females), changes in clinical biochemistry parameters, organ weight effects and histopathological findings. This study is less well documented than the one by Matsumoto et al. (2013) and is therefore evaluated as supporting evidence only.
The most sensitive endpoint for DNEL derivation is fertility, as is demonstrated in a screening study for reproductive / developmental toxicity (Matsumoto et al., 2013) according to OECD TG 421. DPPD was applied to rats at 8, 50 and 300 mg/kg bw/d by gavage. Gestation times were significantly elongated in females in the 50 and 300 mg/kg group. From gestation day 22 onwards, severe clinical signs (pale skin, piloerection, hypothermia), mortality, dystocia were observed in females in the 300 mg/kg group. Several offspring parameters were dose-dependently decreased, especially in the 300 mg/kg group: no. of pups born, delivery index, no. of live pups, birth index and live birth index. None of these changes was statistically significant.
The NOAEL with regard to maternal toxicity was 50 mg/kg in this study (based on mortality and clinical signs in the highest dose group), and the NOAEL with regard to reproductive toxicity was 8 mg/kg (elongated gestation times at higher doses).
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- hazard unknown but no further hazard information necessary as no exposure expected
Additional information - General Population
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