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Diss Factsheets
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EC number: 220-237-5 | CAS number: 2680-03-7
- 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:
- 0.207 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):
- 42.5
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 8.82 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- No repeated dose inhalation toxicity study available.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 3.4
- Justification:
- Extrapolation from sub-acute to chronic exposure (Batke et al., 2011)
- 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.
- AF for intraspecies differences:
- 5
- Justification:
- Default assessment factor
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 2.5
- Justification:
- Recommended in REACh Guidance document R.8 (This factor will also cover any uncertainties due to the limited parameters examined in the OECD 421 study)
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:
- 357 µg/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):
- 28
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 10 mg/kg bw/day
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 1.4
- Justification:
- Extrapolation from sub-chronic to chronic exposure (Batke et al., 2011)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Assessment factor for allometric scaling
- AF for intraspecies differences:
- 5
- Justification:
- Default assessment factor
- AF for the quality of the whole database:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no DNEL required: short term exposure controlled by conditions for long-term
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:
- medium hazard (no threshold derived)
Additional information - workers
Kinetics (absorption figures for oral, dermal and inhalation route of exposure)
No data on absorption are available. According to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, it is proposed in the absence of route-specific information on the starting route, to include a default factor of 2 in the case of oral-to-inhalation extrapolation. However, based on the available acute oral and inhalative toxicity studies, there is no indication that oral and inhalative uptakes differ in a way that would justify the use of this default factor. Therefore, a factor 1 will be taken forward to the DNEL derivation.
Acute toxicity
N,N-dimethylacrylamide is classified for acute oral and dermal toxicity. As no high peak exposures occur for the oral and dermal routes, derivation of a DNELacutefor these routes is not necessary.
N,N-dimethylacrylamide is not classified for acute inhalation toxicity, and, therefore, derivation of a DNELacutefor inhalation is not necessary.
Irritation/corrosion and sensitisation
The substance is not irritating to the skin, but irritating to eyes. The substance is not classified as sensitising to skin.
Repeated dose toxicity
The study considered for DNEL derivation (oral and inhalation) of N,N-dimethylacrylamide is the GLP-compliant Reproduction/Developmental Toxicity Screening Test according to OECD 421 in which N,N-dimethylacrylamide was given to rats by oral gavage (BASF SE 2013). Initially, groups of 10 male and 10 female Wistar rats (F0 animals) received the test substance, as a solution in water, at dose levels of 5, 15 and 45 mg/kg bw/day. Because all animals given 45 mg/kg/day lost weight during the first study week, the dose was reduced from 45 to 30 mg/kg bw/day from day 7 onwards. Rats of the control group received the vehicle, water, alone. The duration of treatment covered a 2-week pre-mating and mating period for both sexes and the entire gestation period as well as 4 days of lactation in female animals followed by an additional treatment until one day before sacrifice (total length of treatment period: males 29 days, females 50 days). The dailyclinical observations revealed treatment-related signs of toxicity in all males and females at 45/30 mg/kg/day (poor general condition, closed eyelids, piloerection and reduced attention after dosing at the beginning of the pre-mating phase). Food consumption was significantly reduced at 45/30 mg/kg/day in males (pre-mating period) and females (pre-mating period and first week of gestation). During the pre-mating period, growth was retarded in males at 45/30 mg/kg/day and, dose-dependently, in females at 15 and 45/30 mg/kg/day. Mean body weights of these animals remained lower compared to controls until the end of the study (mean terminal body weights were decreased by about 10%). The absolute weights of the testes and epididymides were not affected by treatment. Necropsy and histopathological examination (of the testes, epididymides and ovaries) revealed no treatment-related changes.Under the conditions of this Reproduction/Developmental Toxicity Screening Test the oral administration by gavage of N,N-dimethylacrylamide to male and female Wistar rats revealed signs of systemic toxicity at dose levels of 15 mg/kg bw/day (reduced body weight) and above (reduced body weight and clinical signs). Thus, the no observed adverse effect level (NOAEL) for general systemic toxicity was 5 mg/kg bw/day for male and female animals.
The study considered for DNEL derivation (dermal) of N,N-dimethylacrylamide is the 13-week repeated dermal dose toxicity GLP study comparable to OECD guideline 411. Groups of ten male and ten female Sprague-Dawley rats were dosed with N,N-dimethylacrylamide under occlusive conditions. Initially, the doses were set at 10, 200 and 500 mg/kg bw/day. However, after six days of administration, it was evident that the highest dose exceeded the maximum tolerated dose since it resulted in overt systemic toxicity (i.e., convulsions, dramatically reduced body weight, body weight gain and food consumption) and two deaths. Therefore, the mid and high dose levels were reduced to 75 and 250 mg/kg bw/day, respectively. The animals that died were replaced with naive animals and the surviving high dose rats were allowed 2 days of rest/recovery prior to administration of the new dose level (i.e., 250 mg/kg bw/day). Salient clinical signs associated with dose levels at or above 250 mg/kg bw/day, especially among females, consisted of hypothermia (after the first dose only), hyperexcitability, piloerection, hunched posture, emaciation, as well as convulsions and death of 2 females. No treatment-related signs of dermal irritation were observed at the application site. No test article-related changes were observed in the tests (grip strength, foot splay and rotorod performance) used to evaluate peripheral neuropathy.
Food consumption was significantly reduced during the first week of treatment (i.e., prior to reducing the dose levels) in the mid and high dose groups. Following reduction of the doses, food consumption was unaffected except for a single reduction noted during week 8 in the high dose males. Treatment-related decreases in body weight and/or body weight gain were observed in the high dose rats for the duration of the study.
Treatment-related changes observed in hematology parameters consisted of decreased total erythrocyte count, accompanied by increases in mean corpuscular volume, mean corpuscular hemoglobin and platelets in females and increases in relative and absolute mature neutrophil counts in both sexes. Alterations in select clinical chemistry and urology parameters, organ weights and organ-to-body weighs ratios were detected in the high dose animals. Test article-related histopathological changes were confined to the kidneys of mid and high dose males and consisted of minimal nephropathy and renal pelvis dilatation. No histopathological evidence of neurotoxicity was observed in the test article-treated rats.
In conclusion, based on the results from this study, the NOAEL is 10 mg/kg bw/day.
Mutagenicity
The substance was negative in an Ames test and positive in both an in vitro chromosomal aberration test and a mouse lymphoma assay. This result was indicative of in vitro clastogenicity. The HPRT assay was negative, as was the in vivo micronucleus test.
Based on these available studies it can be concluded that N,N-Dimethylacrylamide is not mutagenic.
Reproduction toxicity
In the GLP compliant combined reproduction/developmental toxicity screening test in Wistar rats (according to OECD 421), the NOAEL for reproductive performance, fertility and developmental toxicity was 30 mg/kg bw/day (the highest dose tested). Since this value is higher than the NOAEL for general systemic toxicity in this study,no DNEL has to be derived for developmental and reproductive toxicity.
DNEL derivation
For short-term toxicity, no DNEL needs to be derived for all routes of exposure.
For long-term oral toxicity, regarding systemic effects, a NOAEL of 5 mg/kg bw was observed in a reproduction/developmental toxicity screening test in rats (OECD 421).
For long-term dermal toxicity, regarding systemic effects, a NOAEL of 10 mg/kg bw was observed in a 13-week subchronic repeated dose toxicity in rats (OECD 411).
Long-term inhalation toxicity data is not available.
To correct the (modified) dose-descriptors for duration of exposure, the values from the evaluation of Batke et al. (2011) were used instead of the default values proposed in the REACH guidance (Table R. 8-5).Within the ERASM project, time-extrapolation factors were evaluated with the database RepDose that currently contains about 670 substances and 2200 studies on repeated-dose toxicity. It has been shown that as long as the material is soluble, the sub-acute to sub-chronic factor was 1.5 (rather than 3), the sub-acute to chronic factor was 3.4 (rather than 6), and the sub-chronic to chronic factor was 1.4 (rather than 2) (Batke et al, 2011). In addition, in the oralReproduction/Developmental Toxicity Screening Test, used to derive the long-term oral and inhalation DNELs, the female rats were exposed for a longer period of time than in a standard sub-acute study(up to 50 days instead of 28 days). Therefore, a factor of 3.4 is sufficient for extrapolation to chronic exposure.
Reference:
Batke M, Escher S, Hoffmann-Doerr S, Melber C, Messinger H, Mangelsdorf I (2011). Evaluation of time extrapolation factors based on the database RepDose. Toxicology Letters 205, 122– 129.
Worker DNELs
Long-term –inhalation, systemic effects(based on oral gavage reproduction/developmental toxicity screening test in rats (OECD 421)).
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 5 mg/kg bw/day |
Based on systemic toxicity at 15 mg/kg bw (reduced body weight) and above (reduced body weight and clinical signs). |
Step 2) Modification of starting point |
1
0.38 m3/kg bw
6.7 m3/10 m3 |
The available acute oral and inhalation studies do not indicate differences in uptake that would justify the use of the default factor of 2 proposed in the REACH guidance.
Standard respiratory volume of a rat, corrected for 8 h exposure, as proposed in the REACH Guidance (R.8.4.2)
Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3). |
Modified dose-descriptor |
5 / 1 / 0.38 x (6.7/10) = 8.82 mg/m3 |
|
Step 3) Assessment factors |
|
|
Interspecies |
1 |
No allometric scaling has to be applied in case of oral to inhalation route to route extrapolation. |
Intraspecies |
5 |
Default assessment factor for worker |
Exposure duration |
3.4 |
Extrapolation from sub-acute to chronic exposure(Batke et al., 2011) |
Dose response |
1 |
|
Quality of database |
1 |
|
Remaining uncertainties |
2.5 |
Recommended in REACH Guidance document R.8 (This factor will also cover any uncertainties due to the limited parameters examined in the OECD 421 study) |
DNEL |
Value |
|
|
8.82 / (1 x 5 x 3.4 x 1 x 1 x 2.5) = 8.82 / 42.5 =0.207mg/m3 |
Long-term - inhalation, local effects
No data are available based on which a DNEL for local effects can be derived. There are also no data to suggest that the substance may cause local effects by inhalation exposure.
Long-term – dermal, systemic effects(based on 90 day repeated dose dermal toxicity study with rats)
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 10 mg/kg bw/day |
Based on minimal renal toxicity, alterations in clinical pathology parameters and significant alterations in body weight parameters. |
Step 2) Modification of starting point |
|
|
Modified dose-descriptor |
10 mg/kg bw/day |
|
Step 3) Assessment factors |
|
|
Interspecies |
4 |
Assessment factor for allometric scaling |
Intraspecies |
5 |
Default assessment factor for worker |
Exposure duration |
1.4 |
Extrapolation sub-chronic to chronic exposure (Batke et al., 2011) |
Dose response |
1 |
|
Quality of database |
1 |
|
DNEL |
Value |
|
|
10 / (4 x 5 x 2 x 1 x 1) = 10 / 28 =357 µg/kg bw/day |
Long-term - dermal, local effects
No local effects were observed in the available 90 day repeated dose dermal toxicity study.The substance is not irritating to skin and not classified as sensitising to skin.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.051 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):
- 85
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 4.35 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- No repeated dose inhalation toxicity study available.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 3.4
- Justification:
- Extrapolation from sub-acute to chronic exposure (Batke et al., 2011)
- 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.
- AF for intraspecies differences:
- 10
- Justification:
- Default assessment factor
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 2.5
- Justification:
- Recommended in REACh Guidance document R.8 (This factor will also cover any uncertainties due to the limited parameters examined in the OECD 421 study)
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:
- 179 µg/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):
- 56
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 10 mg/kg bw/day
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 1.4
- Justification:
- Extrapolation sub-chronic to chronic exposure (Batke et al., 2011)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Assessment factor for allometric scaling.
- AF for intraspecies differences:
- 10
- Justification:
- Default assessment factor
- AF for the quality of the whole database:
- 1
Acute/short term exposure
- Hazard assessment conclusion:
- no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no DNEL required: short term exposure controlled by conditions for long-term
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 14.7 µg/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):
- 340
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 5 mg/kg bw/day
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 3.4
- Justification:
- Extrapolation from sub-acute to chronic exposure (Batke et al., 2011)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- Assessment factor for allometric scaling.
- AF for intraspecies differences:
- 10
- Justification:
- Default assessment factor
- AF for the quality of the whole database:
- 1
- AF for remaining uncertainties:
- 2.5
- Justification:
- Recommended in REACh Guidance document R.8 (This factor will also cover any uncertainties due to the limited parameters examined in the OECD 421 study)
Acute/short term exposure
- Hazard assessment conclusion:
- other toxicological threshold
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- medium hazard (no threshold derived)
Additional information - General Population
General population DNELs
Long-term – oral, systemic effects (based on oral gavage reproduction/developmental toxicity screening test in rats (OECD 421)).
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 5 mg/kg bw/day |
Based on systemic toxicity at a 15 mg/kg bw (reduced body weight) and above (reduced body weight and clinical signs). |
Step 3) Assessment factors |
|
|
Interspecies |
4 |
Assessment factor for allometric scaling. |
Intraspecies |
10 |
Default assessment factor for general population |
Exposure duration |
3.4 |
Extrapolation from sub-acute to chronic exposure (Batke et al., 2011) |
Dose response |
1 |
|
Quality of database |
1 |
|
Remaining uncertainties |
2.5 |
Recommended in REACH Guidance document R.8 (This factor will also cover any uncertainties due to the limited parameters examined in the OECD 421 study) |
DNEL |
Value |
|
|
5 / (4 x 10 x 3.4 x 1 x 1 x 2.5) = 5 / 340 =14.7 µg/kg bw/day |
Long-term – inhalation, systemic effects (based on oral gavage reproduction/developmental toxicity screening test in rats (OECD 421)).
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 5 mg/kg bw/day |
Based on systemic toxicity 15 mg/kg bw (reduced body weight) and above (reduced body weight and clinical signs). |
Step 2) Modification of starting point |
1
1.15 m3/kg bw
|
The available acute oral and inhalation studies do not indicate differences in uptake that would justify the use of the default factor of 2 proposed in the REACH guidance.
Standard respiratory volume of a rat, corrected for 24 h exposure, as proposed in the REACH Guidance (R.8.4.2)
|
Modified dose-descriptor |
5 / 1 x (1/1.15) = 4.35 mg/m3 |
|
Step 3) Assessment factors |
|
|
Interspecies |
1 |
No allometric scaling has to be applied in case of oral to inhalation route to route extrapolation. |
Intraspecies |
10 |
Default assessment factor for general population |
Exposure duration |
3.4 |
Extrapolation from sub-acute to chronic exposure (Batke et al., 2011) |
Dose response |
1 |
|
Quality of database |
1 |
|
Remaining uncertainties |
2.5 |
Recommended in REACH Guidance document R.8 (This factor will also cover any uncertainties due to the limited parameters examined in the OECD 421 study) |
DNEL |
Value |
|
|
4.35 / (1 x 10 x 3.4 x 1 x 1 x 2.5) = 4.35 / 85 =0.0512mg/m3 |
Long-term - inhalation, local effects
No data are available based on which a DNEL for local effects can be derived. There are also no data to suggest that the substance may cause local effects by inhalation exposure.
Long-term – dermal, systemic effects (based on 90 day repeated dose dermal toxicity study with rats)
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 10 mg/kg bw/day |
Based on minimal renal toxicity, alterations in clinical pathology parameters and significant alterations in body weight parameters. |
Step 2) Modification of starting point |
|
|
Modified dose-descriptor |
10 mg/kg bw/day |
|
Step 3) Assessment factors |
|
|
Interspecies |
4 |
Assessment factor for allometric scaling. |
Intraspecies |
10 |
Default assessment factor general population |
Exposure duration |
1.4 |
Extrapolation sub-chronic to chronic exposure (Batke et al., 2011) |
Dose response |
1 |
|
Quality of database |
1 |
|
DNEL |
Value |
|
|
10 / (4 x 10 x 2 x 1 x 1) = 10 / 80=179 µg/kg bw/day |
Long-term - dermal, local effects
No local effects were observed in the available 90 day repeated dose dermal toxicity study. The substance is not irritating to skin and not classified as sensitising to skin.
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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