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EC number: 946-533-0 | CAS number: -
- 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
Endpoint summary
Administrative data
Description of key information
Oral LD50 > 2000 mg a.i./kg bw; OECD TG 423 / Method B.1, rat; oral: gavage; RL1, GLP
Dermal LD50 > 2000 mg a.i./kg bw; OECD TG 402 / Method B.1, rat; RL1, GLP; read-across: Amphopropionate C8
Inhalation: no relevant route of exposure
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2015-08-18 to 2015-09-17
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
- Version / remarks:
- 2008
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Version / remarks:
- 17 December 2001
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- acute toxic class method
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 147-183 g
- Fasting period before study: overnight
- Housing: in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): ad libitum (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- MAXIMUM DOSE VOLUME APPLIED: 4.88 mL/kg
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test item, 750 mg/kg (equivalent to 300 mg
active ingredient/kg body weight) was chosen as the starting dose. - Doses:
- 750 mg/kg (equivalent to 300 mg a.i. /kg)
5000 mg/kg (equivalent to 2000 mg a.i./kg) - No. of animals per sex per dose:
- 3 females in the 750 mg/kg (equivalent to 300 mg a.i. /kg) group
2x3 females in the 5000 mg/kg (equivalent to 2000 mg a.i./kg) group - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 30 minutes, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded prior to dosing and 7 and 14 days after treatment.
- Necropsy of survivors performed: yes - Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- act. ingr.
- Mortality:
- none
- Clinical signs:
- other: No signs of systemic toxicity were noted during the observation period.
- Gross pathology:
- No abnormalities were noted at necropsy.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The acute oral LD50 of Amphopropionates C12 -18 in female Wistar rats was estimated to be greater than 2000 mg a.i./kg bw).
- Executive summary:
In an acute oral toxicity study according to OECD Guideline 423 (2001) and EU Method B1., groups of three fasted female young adult Wistar rats were given a single oral dose of Amphopropionates C12 -18 (40% a.i.) at doses of 300 and 2000 mg a.i./kg bw and were observed for 14 days.
No mortality occurred and no signs of systemic toxicity were observed.
Oral LD50 females > 2000 mg a.i./kg bw
Based on these results, Amphopropionate C12 -18 does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- Guideline study without deviations; RL1; GLP
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 2007-05-09 to 2007-05-23
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- Version / remarks:
- 1992
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Version / remarks:
- 1987
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: none
- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cageenrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiaten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: Acclimatization period was at least 5 days before start of treatment under laboratory conditions. During the acclimatization period the animals were group housed in Macrolon cages (MIV type).
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.8 - 23.0°C
- Humidity (%): 39 - 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 09 May 2007 To: 23 May 2007 - Type of coverage:
- occlusive
- Vehicle:
- water
- Details on dermal exposure:
- TEST SITE
- Area of exposure: 5x7 cm
- % coverage: 10%
- Type of wrap if used: The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1 D), successively covered with aluminum foil and Caban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only
REMOVAL OF TEST SUBSTANCE
24 hours after application the dressings were removed and the skin cleaned of residual test substance using tap water
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3738 mL/kg; 2024 mg a.i./kg bw
- Concentration (if solution): 50.6%
- Constant volume or concentration used: yes - Duration of exposure:
- 24 hours
- Doses:
- 2024 mg a.i./kg bw
- No. of animals per sex per dose:
- 5 males and 5 females
- Control animals:
- not required
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality: Twice daily; Body weights: Days 1 (pre-administration), 8 and 15; clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15
- Necropsy of survivors performed: yes - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- act. ingr.
- Mortality:
- No mortality occurred.
- Clinical signs:
- other: Lethargy, flat posture, piloerection (head), chromodacryorrhoea (snout) and/or ptosis was noted among the animals. The animals had recovered from the symptoms between Days 2 and 3. Focal erythema, scars, scales and/or scabs were seen in the treated skin-
- Gross pathology:
- No abnormalities were found at macroscopic post mortem examination of the animals.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The dermal LD50 value of Amphopropionate C8 in Wistar rats was established to exceed 2000 mg a.i./kg body weight.
- Executive summary:
In an acute dermal toxicity study according to OECD guideline 402 (1987) and EU Method B.3 (1992), groups of young adult Wistar rats (5 males and 5 females) were dermally exposed to Amphopropionate C8 (50.6% a.i.) for 24 hours to the limit dose of 2024 mg a.i./kg bw. Animals then were observed for 14 days.
No mortality occurred. Lethargy, flat posture, piloerection (head), chromodacryorrhoea (snout) and/or ptosis was noted among the animals. The animals had recovered from the symptoms between Days 2 and 3. Focal erythema, scars, scales and/or scabs were seen in the treated skin-area of the females during the observation period.
Dermal LD50 Males > 2000 mg/kg bw
Females > 2000 mg/kg bw
Based on these results, Amphopropionate C8 does not have to be classified and has no obligatory labelling requirement for dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- Guideline study without deviations; RL1; GLP
Additional information
Acute oral toxicity
In an acute oral toxicity study according to OECD Guideline 423 (2001) and EU Method B.1, groups of three fasted female young adult Wistar rats were given a single oral dose of Amphopropionates C12 -18 (40% a.i.) by gavage at doses of 300 and 2000 mg a.i./kg bw and were observed for 14 days. No mortality occurred and no signs of systemic toxicity were observed.
Oral LD50 females > 2000 mg a.i./kg bw
In an acute oral toxicity study similar to OECD Guideline 401 (study performance before implementation of OECD TG 401(1981) and GLP), 5 male and 5 female Sprague Dawley SPF albino rats weighing 100 - 120 g were given a single oral dose of Amphopropionates C12 -18 (40% a.i.) at a concentration of 16 mL/kg bw and observed for 14 days. The test substance was administered by gavage and undiluted.
Four of ten animals died. No effects on body weights were observed. Hunched position, rough fur, paleness of extremities, diarrhea, increased lacrimation, slight lethargy and ataxia were observed. Gross pathological examinations at 14 days p.a. (terminal necropsy) revealed a moderate hyperemia, mild haemorrhagic oedema of the lungs, moderate hyperemia of the liver and a local swelling of the cutaneous gastric mucosa.
Oral LD50 Males and Females > 6611 mg/kg bw
(> 16 mL/kg bw; based on product, recalculated with a density 1.033 g/mL and a solid content of 40 %).
Similar results were obtained with the closely related source substances Amphopropionate C8 and Amphoacetates C8-C18. These data are included into the dossier for the justification of read-across for other endpoints.
In an acute oral toxicity study according to OECD Guideline 423 (2002) and EU Method B1., two groups of three fasted female young adult Wistar rats were given a single oral dose of Amphopropionate C8 (50.6% a.i.) at the limit dose 2024 mg a.i./kg bw and were observed for14 days. No mortality occurred. Hunched posture was noted among the animals on Day 1.
Oral LD50 females > 2000 mg a.i./kg bw
The LD50 of Amphoacetates C8-C18 in rat was in the range of 34 - 44.5 ml/kg (aqueous solution) in several studies similar to OECD Guideline 401 (performed before implementation of OECD TG 401(1981) and GLP).
Acute inhalation toxicity
Given that inhalation is not a relevant route of exposure, testing by the inhalation route is not necessary according to REACH Regulation Annex VIII 8.5.2 Column 2. Inhalation is not a relevant route of exposure to Amphopropionates C12-18. This applies to both workers and the general population and is due to the physic-chemical properties of the substance and the nature of the products where it is used. Vapourisation needs not to be considered due to the substance’s very low vapour pressure of 8E-21 Pa at 25°C. The generation of aerosols is excluded by technical means or product design. The substance is not used in spray applications. The most likely route of human exposure for workers and consumers is the dermal route. Results of laboratory animal studies show a low acute toxicity after oral exposure. Therefore the acute intrinsic toxic activity of the substance is considered to be low. The occurrence of a systemic toxicity relevant to humans after inhalation is unlikely and therefore the conduct of an acute inhalation toxicity study is unjustified.
Acute dermal toxicity
According to a Draft Commission Regulation amending Annexes VII and VIII to Regulation (EC) No 1907/2006 (Reference: G/TBT/N/EU/317) testing by the dermal route does not need to be conducted if the substance does not meet the criteria for classification as acutely toxic or STOT SE by the oral route and no systemic effects have been observed inin vivostudies with dermal exposure (e.g. skin irritation, skin sensitisation).
Amphopropionates C12-18 have a low acute oral toxicity (LD50 > 2000 mg/kg bw), and there were no indications for systemic toxicity in other studies with dermal application (in vivo skin irritation and sensitisation studies).
Supporting data are available from the closely related source substance Amphopropionate C8. A justification for read-across is given below.
In an acute dermal toxicity study according to OECD guideline 402 (1987) and EU Method B.3 (1992), groups of young adult Wistar rats (5 males and 5 females) were dermally exposed to Amphopropionate C8 (50.6% a.i.) for 24 hours to the limit dose of 2024 mg a.i./kg bw. Animals then were observed for 14 days.
No mortality occurred. Lethargy, flat posture, piloerection (head), chromodacryorrhoea (snout) and/or ptosis was noted among the animals. The animals had recovered from the symptoms between Days 2 and 3. Focal erythema, scars, scales and/or scabs were seen in the treated skin-area of the females during the observation period.
Dermal LD50 Males > 2000 mg/kg bw
Females > 2000 mg/kg bw
Justification for read-across
For details on substance identity and detailed toxicological profiles, please refer also to the general justification for read-across given at the beginning of the CSR and attached as pdf document to IUCLID section 13.
This read-across approach is justified based on structural similarities. The target and source substances contain the same functional groups. Thus a common mode of action can be assumed.
Structural similarity and functional groups
The target substance Amphopropionates C12-18 is manufactured from fatty acids (C12-18, C18unsatd.) and aminoethylethanolamie (AEEA) to form 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C11-C17 odd-numbered, C17unsatd. alkyl) derivs. This is further reacted with 2-propenoic acid in the presence of sodium hydroxide (alternatively, sodium 2-propenoate can be used) and water. The molar relation between 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C11-C17, C17unsatd. alkyl) derivs. and 2-propenoic acid is somewhat below 1:1. Most of the excess 2-propenoic acid is stripped off by distillation. However, a small amount remains in the aqueous solution.
The source substance Amphopropionate C8 is manufactured from capric acid and aminoethylethanolamine (AEEA) to form 1-(2-Hydroxyethyl)-2-Heptylimidazoline. Excess AEEA is removed from the reaction mixture by distillation at elevated temperature. In a further step 2-propenoic acid is added to form Amphopropionate C8. Most of the excess 2-propenoic acid is stripped off by distillation. However, a small amount remains in the aqueous solution.
Differences
Chain length:
The source substance Amphopropionate C8 contains shorter C chains, whereas the major C chain in the target substance is C12.
In general the absorption declines with increasing alkyl chain length (Ramirez et al. 2001). Therefore the source substance with the shorter alkyl chains is re assumed to represent a worst-case scenario due to higher absorption rates than the target substance.
Degree of unsaturation:
In contrast to the source substance Amphopropionate C8, the target substance Amphopropionates C12-18 contains some amounts of unsaturated C18 chains.
An increase in the degree of unsaturation may lead to a slightly higher irritation potential (HERA, 2002; Stillman, 1975; Aungst, 1989). Apart from that, fatty acids irrespective of their degree of unsaturation are in general non-toxic. Irritation studies are available for the target substance itself, thus, for other endpoints,this difference in composition is of no toxicological relevance.
The provided structural similarities and impurity profiles support the proposed read-across hypothesis with high confidence.
Comparison of acute toxicity data
|
Target substance |
Source substance |
Endpoint |
Amphopropionates C12-18 |
Amphopropionate C8 |
Acute toxicity, oral |
key_Acute toxicity: oral_93820-52-1_8.5.1_Evonik_2015_OECD423
OECD TG 423, rat (Wistar), oral: gavage
LD50(females) > 2000 mg a.i./kg bw
1 (reliable without restriction), GLP |
sup_RA_Acute toxicity_64265-45-8_8.5.1_Evonik_2007_OECD423
OECD TG 423, rat (Wistar), oral: gavage
LD50(females) > 2000 mg a.i./kg bw
1 (reliable without restriction), GLP |
|
sup_Acute toxicity: oral: 93820-52-1_8.5.1_REWO_1979_LD 50 oral
similar to OECD TG 401, rat (Sprague-Dawley), oral: gavage
LD50 > 6611 mg a.i./kg bw
2 (reliable with restrictions), pre-GLP |
|
Acute toxicity, dermal |
No data, read-across |
sup_RA_Acute toxicity_64265-45-8_8.5.3_Evonik_2007_OECD402
OECD TG 402, rat (Wistar), type of coverage: occlusive
LD50 > 2000 mg a.i./kg bw
1 (reliable without restriction), GLP |
The acute oral LD50 of Amphopropionates C12 -18 in female Wistar rats was > 2000 mg a.i./kg bw). The source substance Amphopropionate C8 was of similarly low acute toxicity via the oral route.
No experimental data on acute dermal toxicity are available for the target substance. However, in an acute dermal toxicity study Amphopropionate C8 the dermal LD50 was > 2000 mg/kg bw/d.
Quality of the experimental data of the analogues:
The available data are adequate and sufficiently reliable to justify the read-across approach.
The studies were conducted according to OECD Guidelines 423 and 402, respectively, or similar to OECD Guideline 401, and are reliable or reliable with restrictions (RL1-2).
The test materials used in the respective studies represent the source substance as described in the hypothesis in terms of substance identity and minor constituents.
Overall, the study results are adequate for the purpose of classification and labelling and risk assessment.
Conclusion
The structural similarities between the source and the target substances presented above and in more detail in the general justification for read-across support the read-across hypothesis. Adequate and reliable scientific information indicates that the source and target substances have similar toxicity profiles for the endpoint acute toxicity based on the similarly low acute toxicity via the oral route.
Thus, the results obtained with the source substance Amphopropionate C8 in the acute dermal toxicity study are considered to be also relevant for the target substance Amphopropionates C12 -18.
References
Aungst, 1989. Structure/Effect Studies of Fatty Acid Isomers as Skin Penetration Enhancers and Skin Irritants. Pharmaceutical Research, March 1989, Volume 6, Issue 3, pp 244-247
HERA, 2002: Fatty Acid Salts – Human Health Risk Assessment
Ramírez M, Amate L,Gil A. Absorption and distribution of dietary fatty acids from different sources. Early Human Development 2001 Nov; 65 Suppl:S95-S101
Stillman et al., 1975. Relative irritancy of free fatty acids of different chain length. Contact Dermatitis. 1975;1(2):65-9.
Justification for classification or non-classification
Based on the available data, Amphopropionates C12 -18 does not have to be classified and has no obligatory labelling requirement for acute oral, dermal or inhalation toxicity according to Regulation (EC) No 1272/2008).
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.