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EC number: 939-457-4 | CAS number: 1469983-50-3
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Description of key information
LD50 (rat, oral) = 3020 (females) or 2950 (genders combined) mg/kg bw
LD50 (mouse, oral) = ca. 3150 mg/kg
LD50 (rat, dermal) > 2000 mg/kg
(expressed as mg active ingredient)
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:
- supporting study
- Study period:
- 25 May 1995 - 31 July 1995
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
- Deviations:
- yes
- Remarks:
- 2000 mg/kg bw of test solution administered, equivalent to 830 mg active ingredient/kg bw (41.5%)
- GLP compliance:
- yes
- Test type:
- fixed dose procedure
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, supplied by Criffa, S.A., Barcelona, Spain
- Age at study initiation: 4 weeks upon arrival
- Weight at study initiation: 107-122 g upon administration
- Fasting period before study: Food removed approx. 18 hours before administration, until approx. 3 hours after
- Housing: in makrolon cages (55 x 32.7 x 19 cm) with sawdust bedding (replaced by wire floor during fasting period), 5 rats of the same sex/cage
- Diet: Standard rat diet UAR A04C ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 (occasionally reaching 26°C)
- Humidity (%): 40-70 (occasionally reaching 32-39% or 71-86%)
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12 / 12 (07.00 am-07.00 pm)
IN-LIFE DATES: From: june 21st, 1995 To: July 14th, 1995 - Route of administration:
- oral: gavage
- Vehicle:
- other: bidistilled water
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 200 mg Betadet SHR/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: Not provided
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw - Doses:
- 2000 mg test solution/kg bw
- No. of animals per sex per dose:
- 1 female (preliminary assay)
5 males + 5 females (main assay) - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations: frequently during the day of administration, at least twice a day for the remainder of the observation period
- Frequency of weighing: on days 0 (administration), 1, 2, 3, 7, and 14 (at necropsy)
- Necropsy of survivors performed: yes (main study)
- Other examinations performed: clinical signs, body weight - Statistics:
- Not included
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Remarks:
- Betadet SHR
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 830 mg/kg bw
- Based on:
- act. ingr.
- Remarks:
- based on 41.5% purity
- Mortality:
- No mortality observed.
- Clinical signs:
- other: Slightly soft feces noted among treated animals on the day of dosing. No other clinical signs observed for the remainder of the observation period.
- Gross pathology:
- No macroscopic abnormalities observed.
- Interpretation of results:
- Category 5 based on GHS criteria
- Conclusions:
- The oral LD50 in rats was higher than 2000 mg Betadet SHR/kg bw, equivalent to approximately 830 mg active ingredient/kg bw.
- Executive summary:
Cocamidopropyl hydroxysultaine, as a 41.5% solution, has been tested for acute oral toxicity in Wistar rats. The test article was administered as a single oral dose by gavage. One group of 5 rats per sex received a dose of 2000 mg test solution/kg bw. Examinations for mortality and clinical signs were performed daily during the 14 -day study period. Animals were necropsied at the end of the observation period.
No mortality was observed. Slightly soft feces were noted among treated animals on the day of dosing, but no other clinical signs were observed over the rest of the observation period. Bodyweight was not affected by the administration. No relevant changes were seen at necropsy.
The oral LD50 in rats was therefore higher than 2000 mg test solution/kg bw, equivalent to approximately 830 mg active ingredient/kg bw.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1990
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- other: OECD test guideline 401 ‘Acute Oral Toxicity’ deleted on 17th December 2002
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: not provided
- Weight at study initiation: 171-276 g (males), 164-216 g (females)
- Fasting period before study: from 16 hours before until 3-4 hours after administration
- Housing: up to a maximum of 5 rats per cage (Macrolon type III cage)
- Diet (e.g. ad libitum): not detailed
- Water (e.g. ad libitum): not detailed
- Acclimation period: at least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 2
- Humidity (%): 50-85
- Air changes (per hr): not detailed
- Photoperiod (hrs dark / hrs light): 12 / 12 (7.00 am-7.00 pm)
IN-LIFE DATES: Not provided - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- VEHICLE
No vehicle used (solution administered as such with different dosing volumes)
MAXIMUM DOSE VOLUME APPLIED:
1000 mg/kg: 2.33 mL/kg bw
2000 mg/kg: 4.65 mL/kg bw
3000 mg/kg: 6.98 mL/kg bw - Doses:
- 1000, 2000 and 3000 mg active component/ kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Examinations performed: mortality (over the 24-hour post-dosing period, and then daily), clinical signs (daily), body weights (just before dosing, on days 7 and 14)
- Necropsy of survivors performed: yes - Statistics:
- The method of Finney D.Y., Probit Analysis (3rd ed., Cambridge, 1971) was used for calculating the oral LD50.
- Preliminary study:
- One animal died within 24 hours of dosing at 2000 mg/kg
- Sex:
- male
- Dose descriptor:
- LD50
- Remarks on result:
- other: Could not be calculated because only at the high dose pre-terminal deaths were lower than 100% and higher than 0%
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 3 020 mg/kg bw
- Based on:
- act. ingr.
- Remarks on result:
- other: at 24 h and 14 days after dosing
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 2 950 mg/kg bw
- Based on:
- act. ingr.
- Remarks on result:
- other: at 24 h and 14 days after dosing
- Mortality:
- See table below
- Clinical signs:
- other: Up to 3 days post-dosing, reduced general activity was observed at 3000 mg/kg, together with squatting position, reduced skin turgor, cyanosis, diarrhea and piloerection on some occasions.
- Gross pathology:
- - 2000 and 3000 mg/kg: animals killed in extremis within 24 hours post-dosing showed hemorrhagic and lytic alterations in the gatro-intestinal tract and/or yellow-orange discoloration of lungs and/or reddish pelvis at macroscopic examination.
- At terminal sacrifice (14 days post-dosing): no test-article abnormalities noted at necropsy. - Interpretation of results:
- Category 5 based on GHS criteria
- Conclusions:
- The oral LD50 in rats was calculated to be 3020 or 2950 mg active ingredient/kg bw, for females or both genders, respectively, at 24 hours and 14 days after administration. The oral LD50 in male rats could not be calculated because deaths occurred only in the high-dose group.
- Executive summary:
Cocamidopropyl hydroxysultaine, as a 42% aqueous solution, has been tested for acute oral toxicity in Wistar rats. The test article was administered as such using different dosing volumes to reach the desired dose levels. Three groups of 5 rats per gender received a dose volume of 2.33, 4.65 and 6.98 mL/kg, equivalent to 1000, 2000 and 3000 mg active ingredient/kg, respectively. Examinations for mortality and clinical signs were performed daily during the 14-day study period. Body weights were measured just before dosing, and 7 and 14 after dosing. A macroscopic examination was performed at the necropsy of survivors on day 14.
A high incidence of pre-terminal deaths occurred at 2000 and 3000 mg/kg, whereas no death occurred at 1000 mg/kg: 3/5 male rats were found dead or sacrificed in extremis within 24 hours of dosing in the 3000 mg/kg dose group, and 2/5 female rats were found dead or sacrificed in extremis within 24 hours of dosing in each of the 2000 mg/kg and 3000 mg/kg dose groups. Marked clinical signs, such as general reduced activity together with diarrhea, squatting position, piloerection and/or reduced skin turgor were observed at 3000 mg/kg within 3 days post-dosing. Body weight gain was normal in surviving animals over the observation period. Hemorrhagic and lytic mucous membrane alterations in the gastro-intestinal tract, considered test-article related, were observed at necropsy in animals found dead or sacrificed in extremis within 24 hours of dosing in the 2000 mg/kg and 3000 mg/kg dose groups. At terminal sacrifice, no test-related macroscopic findings were observed in the other animals.
The oral LD50 in rats was calculated to be 3020 or 2950 mg active ingredient/kg bw, for females or both genders, respectively, at 24 hours and 14 days after administration. The oral LD50 in male rats could not be calculated because deaths occurred only in the high-dose group.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1977
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Test procedure in accordance with national standard methods at the time of the study, conducted in the mouse instead of the rat, which is the preferred rodent test species as per Regulation 440/2008.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
- Deviations:
- yes
- Remarks:
- Mouse used as test species instead of Rat - No necropsy performed - 5 days of observation period
- GLP compliance:
- no
- Test type:
- fixed dose procedure
- Limit test:
- no
- Species:
- mouse
- Strain:
- other: CFW
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Strain: Carworth
- Weight at study initiation: 18-21 grams
- Housing: 5 mice per cage
- Diet: ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
Not specified
IN-LIFE DATES
Not specified - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- The test material was administered by means of a rigid stomach tube.
Prior to administration, the test material was diluted 1 to 5 in water. - Doses:
- 6, 7.5 and 10 mL test solution/kg bw
- No. of animals per sex per dose:
- 10 (unspecified gender)
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 5 days
- Examinations performed: mortality, clinical signs
- Necropsy of survivors performed: no - Statistics:
- The method of Litchfield & Wilcoxon (J. Pharmacol. Exp. Ther. 96: 99, 1949) was used for calculating the oral LD50.
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- 7.5 mL/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 6.5 - <= 8.3
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- ca. 3 150 mg/kg bw
- Based on:
- act. ingr.
- Remarks:
- taking account of the 42% purity of test solution
- Mortality:
- 2/10 mice at 6 mL/kg
5/10 mice at 7.5 mL/kg
8/10 mice at 10 mL/kg - Clinical signs:
- other: No details provided
- Gross pathology:
- Not evaluated
- Interpretation of results:
- Category 5 based on GHS criteria
- Conclusions:
- The oral LD50 in mice was calculated to be 7.5 mL/kg bw, equivalent to approximately 3150 mg active ingredient/kg bw.
- Executive summary:
Cocamidopropyl hydroxysultaine, as a 42% aqueous solution, has been tested for acute oral toxicity in CFW mice (Carworth strain). The test article was administered as a 1 to 5 dilution in water as a single oral dose by gavage. Three groups of 10 mice received a dose volume of 6.0, 7.5 and 10 ml/kg, respectively. Examinations for mortality and clinical signs were performed daily during the 5 -day study period.
Two mice died in the group receiving the lowest dose, 5 mice died in the group receiving 7.5 ml/kg, and 8 mice died in the upper dose group.
The oral LD50 was therefore calculated to be 7.5 mL/kg bw, equivalent to approximately 3150 mg active ingredient/kg bw.
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- 1. HYPOTHESIS FOR THE ANALOGUE APPROACH
C8-C18 AAPHS and C12-18 AAPHS have the same functional groups, and general composition. The main variable resides in the alkyl chain distribution.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical = C8-18 cocamidopropyl hydroxysultaine (EC 939-455-3)
Target chemical = C12-18 cocamidopropyl hydroxysultaine (EC 939-457-4)
3. ANALOGUE APPROACH JUSTIFICATION
The alkyl C-chain distribution of the source chemical significantly overlaps with the one of the target chemical, the C12-alkyl derivative being the major constituent in both chemicals. The structural differences in side C-chains is not expected to lead to significant differences on phys-chem properties.
4. DATA MATRIX: see "Documentation and scientific justification of the read-across approach" in section 13.2 - Reason / purpose for cross-reference:
- read-across source
- Sex:
- male
- Dose descriptor:
- LD50
- Remarks on result:
- other: Could not be calculated because only at the high dose pre-terminal deaths were lower than 100% and higher than 0%
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 3 020 mg/kg bw
- Based on:
- act. ingr.
- Remarks on result:
- other: at 24 h and 14 days after dosing
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 2 950 mg/kg bw
- Based on:
- act. ingr.
- Remarks on result:
- other: at 24 h and 14 days after dosing
- Interpretation of results:
- Category 5 based on GHS criteria
- Conclusions:
- The oral LD50 in rats was calculated to be 3020 or 2950 mg active ingredient/kg bw, for females or both genders, respectively, at 24 hours and 14 days after administration. The oral LD50 in male rats could not be calculated because deaths occurred only in the high-dose group.
Referenceopen allclose all
Dose level (mg/kg) |
Animals |
Observation day (Day 0 = day of administration) |
Bodyweight at necropsy |
||||||
No. |
Gender |
0 |
1 |
2 |
3 |
7 |
14 |
||
2000 |
2 |
M |
122 |
145 |
160 |
169 |
212 |
282 |
282 |
3 |
M |
116 |
140 |
154 |
162 |
203 |
270 |
270 |
|
4 |
M |
116 |
138 |
154 |
159 |
202 |
260 |
260 |
|
5 |
M |
107 |
124 |
141 |
147 |
190 |
256 |
256 |
|
6 |
M |
125 |
149 |
164 |
173 |
216 |
284 |
284 |
|
7 |
F |
117 |
137 |
148 |
154 |
175 |
211 |
211 |
|
8 |
F |
120 |
140 |
149 |
156 |
172 |
200 |
200 |
|
9 |
F |
113 |
133 |
142 |
150 |
167 |
193 |
193 |
|
10 |
F |
109 |
128 |
142 |
150 |
166 |
194 |
194 |
|
11 |
F |
122 |
148 |
158 |
164 |
179 |
207 |
207 |
Bodyweight measurements (in grams, main study)
Dose (mg/kg) |
Post-treatment time |
|||||
Males |
Females |
|||||
24 hours |
7 days |
14 days |
24 hours |
7 days |
14 days |
|
1000 |
0/5 |
0/5 |
0/5 |
0/5 |
0/5 |
0/5 |
2000 |
0/5 |
0/5 |
0/5 |
2/5 |
2/5 |
2/5 |
3000 |
3/5 |
3/5 |
3/5 |
2/5 |
2/5 |
2/5 |
Cumulative Mortality over the 14-day observation period
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 950 mg/kg bw
- Quality of whole database:
- Three Klimisch score 2 studies in 2 different rodent species (two in rats and one in mice) are available, with consistent study results
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:
- key study
- Study period:
- February - August 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approx. 8 weeks old
- Weight at study initiation: 320-348 g (males) - 214-248 g (females)
- Fasting period before study: No
- Housing: By 5 from the same sex and group in polycarbonate cages with stainless steel lids containing autoclaved sawdust, with nylabone used as enrichment
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 8 days (males) - 5 days (females) before application
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 20
- Air changes (per hr): 12 cycles
- Photoperiod (hrs dark / hrs light): 12 / 12
IN-LIFE DATES: From: 05 March 2012 To: 23 March 2012 - Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
- Area of exposure: approx. 7 x 5 cm for males, 6 x 5 cm for females
- % coverage: approx. 10% of total body surface
- Type of wrap if used: Application site covered with aerated hypoallergic dressing
REMOVAL OF TEST SUBSTANCE
No washing
TEST MATERIAL
- Solution applied as is.
- Quantity of test item applied adjusted based on the body weight recorded on the day of application.
- Correction factor of 2.76 used to calculate the dosage volume to be applied taking account of the solution purity. - Duration of exposure:
- 24 hours
- Doses:
- 2000 mg active ingredient/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
. Morbidity / mortality: frequently during hours following application, at least once daily for the remainder of the observation period
. Clinical signs: at least once during first 30 minutes, periodically during first 4 hours, once daily for the remainder of the observation period
. Bodyweight: recorded on the day of group allocation, then on the day of application (day 1) and on days 8 and 15
- Necropsy of survivors performed: yes (spleen was preserved in 10% buffered formalin, stored, and destroyed at finalization of study report) - Statistics:
- No statistical analyses included
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- act. ingr.
- Mortality:
- No unscheduled deaths observed
- Clinical signs:
- other: No clinical signs indicative of systemic toxicity observed. Very slight or well defined erythema noted at application site for 2 females on day 2.
- Gross pathology:
- Enlargement of the spleen was found in all treated animals but was considered incidental as it is part of the normal background in untreated rats of these strain and age.
- Other findings:
- Due to enlargement seen at necropsy, spleens were preserved in 10% buffered formalin and stored. In the absence of toxicological relevance, no histopathology was conducted and these organs were therefore destroyed upon finalization of the study report.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The dermal LD50 in rats was higher than 2000 mg active ingredient/kg bw.
- Executive summary:
Cocamidopropyl hydroxysultaine, as a 36.2% solution (Mackam CBS-50GE), has been tested for acute dermal toxicity in Sprague-Dawley rats. The test article was applied as a single dose under a semi-occlusive dressing for 24 hours. One group of 5 rats per sex received a dose of 2000 mg active ingredient/kg bw. Examinations for mortality and clinical signs were performed daily during the 14 -day study period. Animals were necropsied at the end of the observation period.
No mortality was observed. No clinical signs indicative of systemic toxicity were observed. Very slight or well defined erythema was noted at the application site for 2 females on day 2. Mean bodyweight gain was slightly lower than historical control data for females over the observation period, notably during the first week following application. However, no such changes were observed for males. Enlargement of the spleen was found in all treated animals but was considered incidental as it is part of the normal background in untreated rats of these strain and age.
The dermal LD50 in rats was therefore higher than 2000 mg active ingredient/kg bw.
- Endpoint:
- acute toxicity: dermal
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- 1. HYPOTHESIS FOR THE ANALOGUE APPROACH
C8-C18 AAPHS and C12-18 AAPHS have the same functional groups, and general composition. The main variable resides in the alkyl chain distribution.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical = C8-18 cocamidopropyl hydroxysultaine (EC 939-455-3)
Target chemical = C12-18 cocamidopropyl hydroxysultaine (EC 939-457-4)
3. ANALOGUE APPROACH JUSTIFICATION
The alkyl C-chain distribution of the source chemical significantly overlaps with the one of the target chemical, the C12-alkyl derivative being the major constituent in both chemicals. The structural differences in side C-chains is not expected to lead to significant differences on phys-chem properties.
4. DATA MATRIX: see "Documentation and scientific justification of the read-across approach" in section 13.2 - Reason / purpose for cross-reference:
- read-across source
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- act. ingr.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The dermal LD50 in rats exposed to C8-C18 Cocamidopropyl dimethyl hydroxysultaine was higher than 2000 mg active ingredient/kg bw. By analogy, the same conclusion applies to C12-C18 Cocamidopropyl dimethyl hydroxysultaine.
Referenceopen allclose all
|
Females |
Males |
||
Historical controls |
Treated |
Historical controls |
Treated |
|
Dose level (mg/kg) |
0 |
2000 |
0 |
2000 |
Days 1-8 |
+36 |
+21 |
+45 |
+41 |
Days 8-15 |
+18 |
+16 |
+45 |
+44 |
Days 1-15 |
+55 |
+37 |
+90 |
+84 |
Mean bodyweight gains (grams) during the observation period
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- discriminating dose
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- Recent GLP and OECD test guideline-compliant study (Klimisch score 1)
Additional information
- In the key study (1990), C8 -18 Cocamidopropyl hydroxysultaine was administered by gavage at 1000, 2000 or 3000 mg active ingredient/kg as a 42% active ingredient aqueous solution to 5 rats per gender, kept for a 14-day observation period and then necropsied. A high incidence of pre-terminal deaths occurred at 2000 and 3000 mg/kg, whereas no death occurred at 1000 mg/kg. Marked clinical signs were observed at 3000 mg/kg within 3 days post-dosing. Hemorrhagic and lytic mucous membrane alterations in the gastro-intestinal tract, considered test-article related, were observed at necropsy in animals found dead or sacrificed in extremis within 24 hours of dosing in the 2000 mg/kg and 3000 mg/kg dose groups. The LD50 was calculated to be 3020 or 2950 mg active ingredient/kg bw, for females or both genders, respectively.
- In one supporting study in rats (1995), C8 -18 Cocamidopropyl hydroxysultaine was administered by gavage at the dose of 2000 mg test solution/kg as a 41.5% active ingredient aqueous solution to 5 animals per gender, kept for a 14-day observation period and then necropsied. No mortality, overt sign of toxicity, or relevant bodyweight changes were observed. Therefore, the LD50 was higher than 2000 mg test solution/kg, equivalent to 830 mg active ingredient/kg. In the other supporting study in mice (1978), C12 -18 Cocamidopropyl hydroxysultaine was administered by gavage at the doses of 6, 7.5 or 10 mL/kg as a 42% active ingredient aqueous solution to 10 animals per dose, kept for a 5-day observation period and then necropsied. Mortality occurred from the lowest dose on, and the LD50 was calculated to be 7.5 mL/kg, equivalent to approximately 3150 mg active ingredient/kg. Using the body surface allometry principles, a dose of 3150 mg/kg in mice is globally equivalent to 1575 mg/kg (half the dose) in rats.
Based on the nature of the substance and its likely routes of exposure, the acute toxicity of Cocamidopropyl hydroxysultaine has been tested by oral and dermal routes. As only one mice study by the oral route was available on the registered substance, the dataset was completed with studies conducted on the structural analogue substance C8 -18 cocamidopropyl hydroxysultaine (= source substance EC 939-455-3).
Three Klimisch score 2 studies were available for oral route. One study in rats was used as a key study and the other two (one in rats and one in mice) used as supporting:
One Klimisch score 1 study was available for dermal route and was used as a key study. In this study (2012), C8 -18 Cocamidopropyl hydroxysultaine was applied for 24 hours under semi-occlusive coverage at the dose of 2000 mg active ingredient/kg as a 36.2% active ingredient aqueous solution to 5 rats per gender, kept for a 14-day observation period and then necropsied. No mortality, overt sign of toxicity, or relevant bodyweight changes were observed. Therefore, the LD50 was higher than 2000 mg active ingredient/kg. Based on the absence of mortality or severe clinical signs in rats up to 2000 mg active ingredient/kg, no classification for dermal acute toxicity is warranted. No target organ was identified following a single dermal application in rats.
Justification for selection of acute toxicity – oral endpoint
Study with the highest degree of compliance with presently
recommended test standards.
Justification for selection of acute toxicity – dermal endpoint
Only one study available
Justification for classification or non-classification
Based on the LD50 values obtained in the key study, no classification for oral acute toxicity is warranted according to Reg. (EC) No 1272/2008 (CLP) criteria. This is supported by the high oral LD50 in mice and the absence of mortality or severe clinical signs in rats up to 830 mg active ingredient/kg seen in the other studies under consideration.
In accordance with CLP Regulation (EC) No 1272/2008 criteria, as the dermal LD50 in rats is higher than 2000 mg active ingredient/kg, no classification for dermal acute toxicity is warranted.
No target organ was identified following a single oral or dermal administration in rats.
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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.
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