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Administrative data

Description of key information

Oral


LD50 > 2000 mg/kg bw


Conclusion based on data with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) and considering all available data on acute oral toxicity in the Alkyl Ether Sulfate (AES) category in a Weight-of-Evidence approach.


 


Inhalation


No information required according to the REACH Regulation (EC) No. 1907/2006, Annex VIII, Section 8.5, Column 2, as data on acute oral and acute dermal toxicity are provided.


 


Dermal


LD50 > 2000 mg/kg bw


Conclusion based on data with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) and considering all available data on acute dermal toxicity in the AES category in a Weight-of-Evidence approach.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: CFY (Sprague-Dawley origin)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Interfauna UK Ltd., Huntingdon, UK
- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: 99 - 149 g
- Fasting period before study: overnight prior to dosing
- Housing: housed in groups by sex in metal cages with wire mesh floors
- Diet: standard laboratory rodent diet (Labsure LAD1); ad libitum
- Water (e.g. ad libitum): water not further specified; ad libitum
- Acclimation period: at least 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22
- Humidity (%): 55
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
2000, 3200, 4000, 5000 mg/kg bw
No. of animals per sex per dose:
5
(2 on one of the 4 experimental days (8 apr 1986))
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (main study), 5 days (preliminary study)
- Frequency of observations and weighing: clinical observations were performed after dosing, then at frequent intervals for the remainder of Day1. On subsequent days, the animals were observed once in the morning and again at the end of the experimental day. Body weights were recorded on Day 1 (day of dosing), 8 and 15 and at death.
- Necropsy of survivors performed: yes
- Clinical signs including body weight: yes, recorded
Statistics:
The acude median lethal oral dose (LD50) to male and female rats was calculated using mortality data from the limit test and main study. The calculation method was Finney Probit Analysis (1971). A chi-square test was carried out.
Preliminary study:
Groups of 10 rats (5 males and 5 females) were dosed at 2.0, 3.2, 4.0 and 5.0 g/kg test substance. The LD50 was between 2.5 - 4.0 g/kg bw.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 100 mg/kg bw
Based on:
test mat.
95% CL:
>= 3 700 - <= 4 600
Sex:
male
Dose descriptor:
LD50
Effect level:
4 000 mg/kg bw
Based on:
test mat.
95% CL:
>= 3.3 - <= 4.6
Sex:
female
Dose descriptor:
LD50
Effect level:
4 300 mg/kg bw
Based on:
test mat.
95% CL:
>= 3 700 - <= 5 100
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 870 mg/kg bw
Based on:
act. ingr.
Mortality:
There were deaths among animals dosed at 4000 and 5000 mg/kg bw one hour after dosing or on Day 2 (see Table 1 under "Any other information on results incl. tables."). Autopsy revealed renal pallor in those dosed at 4.0 g/kg and, in two females dosed at 5.0 g/kg, pallor of the liver, spleen and kidneys and the presence of blood in the thoracic or thoracic and abdominal cavities. Body weight losses were also recorded for rats that died.
Clinical signs:
diarrhoea
lethargy (hypoactivity)
salivation
other: piloerection, hunched posture, abnormal gait (waddling), decreased respiratory rate, pallor of extremities, ptosis
Body weight:
lower than 10% body weight loss
Remarks:
One female rat dosed at 4.0 g/kg showed low body weight gain between Days 8 - 15. All other rats achieved anticipated body weight gains throughout the study.
Gross pathology:
No effects.
Other findings:
Recovery, as judged by external appearance and behaviour, was apparently complete by Day 6.

Table 1: Mortalities


 





















































Sex

Dose


(g/kg bw)


Number of deathsTime point after dosing
male2.00/5 
3.20/5 
4.04/5all 2 days (first observation)
5.04/5all 2 days (first observation)
female2.00/5 
3.20/5 
4.02/5all 2 days (first observation)
5.04/52 IDs 1 h, 2 IDs 2 days (first observation)
Interpretation of results:
other: CLP criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
In the present acute oral toxicity study compliant with OECD test guideline 401, administration of the test item lead to mortality at doses 4.0 and 5.0 g/kg in rats. Clinical symptoms occurred from 3.2 g/kg and higher, but resolved at Day 6 after treatment. Based on the results, the LD50 in males and females was set to 2870 mg/kg bw. Due to the experimental set-up, this result can be interpreted as either Acute Toxicity Category 5 (GHS 2017), or unclassified (Regulation (EC) No 1272/2008).
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
range-finder for OECD TG 401
Qualifier:
no guideline required
Principles of method if other than guideline:
Rangefinder for OECD 401.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Doses:
0.5, 1.0, 2.0, 5.0, 10.0 mL/kg bw
No. of animals per sex per dose:
1
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 700 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortality occurred.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
In this range-finding study for OECD TG 401, one rat was dosed at 10000 mg/kg bw (or 2700 mg a.i./kg bw) by oral gavage. No mortality occurred. Therefore, the LD50 of the test substance was set at > 10000 mg/kg bw (or > 2700 mg a.i./kg bw). Therefore, the test substance does not require classification according to GHS 2017 or Regulation (EC) No 1272/2008.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
05 - 19 Aug 1986
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)
Version / remarks:
adopted in 1981 (deleted in 2002)
Deviations:
not specified
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: BOR: WISW (SPF TNO)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, Borchen, DE
- Age at study initiation: not reported
- Weight at study initiation: 103.6 g
- Fasting period: 16 h
- Housing: up to 5 animals per Macrolon type III cage
- Diet: RIO rat diet (Ssniff Spezialfutter GmbH, Soest, DE); ad libitum
- Water: tap water; ad libitum
- Acclimation period: 4 - 8 days
- Method of randomisation in assigning animals to test and control groups: according to a randomized figure table upon distribution to test cages

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 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: 2.408 cm^3/kg

DOSAGE PREPARATION: administered undiluted
Doses:
2500 mg/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: prior to administration, and on Day 1, 7 and 14 after administration
- Necropsy of survivors performed: yes, at the end of the experimental period
- Clinical signs including body weight: yes. Clinical signs were recorded up to 6 h after administration and then daily therafter. The onset, type and duration of toxic symptoms as well as the time point of death were recorded.
Statistics:
The body weight means were calculated. The LD50 was determined according to Litchfield and Wilcoxon with a 95% confidence interval.
Preliminary study:
not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 750 mg/kg bw
Based on:
act. ingr.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortality occurred.
Clinical signs:
diarrhoea
lethargy (hypoactivity)
other: piloerection, hunched posture
Body weight:
lower than 10% body weight loss
Remarks:
There was no effect on body weight.
Gross pathology:
There was no evidence for macroscopic changes at necropsy.
Interpretation of results:
other: CLP criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In the present acute oral toxicity study compliant with OECD test guideline 401 (adopted in 1981, deleted in 2002), the test substance did not lead to mortality in rats when administered orally via gavage at a dose level of 2000 mg/kg bw (or 1750 mg a.i./kg bw). Clinical symptoms included diarrhoae, hunched posture, piloerection and slow movements, but resolved in all animals at the latest after 48 h. Based on the results of the study, the LD50 of the test substance was set at > 2000 mg/kg bw (or > 1750 mg a.i./kg bw). Due to the experimental set-up, this result can be interpreted as either Acute Toxicity Category 5 (GHS 2017), or unclassified (Regulation (EC) No 1272/2008).
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
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:
not specified
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 540 mg/kg bw
Based on:
act. ingr.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortality occurred.
Interpretation of results:
other: CLP criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In the present acute oral toxicity study in rats according to OECD test guideline 401, administration of the test substance via oral gavage at a dose level of 2000 mg/kg bw (or 540 mg a.i./kg bw) did not result in mortality. Therefore, the LD50 of the test substance was established at > 2000 mg/kg bw (or > 540 mg a.i./kg bw) in males and females. Due to the experimental set-up, this result can be interpreted as either Acute Toxicity Category 5 (GHS 2017), or unclassified (Regulation (EC) No 1272/2008).
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
not reported
Control animals:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 380 mg/kg bw
Based on:
act. ingr.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortality occurred.
Interpretation of results:
other: CLP criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In the present acute oral toxicity study compliant with OECD TG 401, rats were dosed orally by gavage with the test substance at a dosage of 1380 mg/kg bw. No mortality occurred. Therefore, the LD50 of the test substance was set to > 200 mg/kg bw (or >1380 mg a.i./kg bw). Due to the experimental set-up, this result can be interpreted as either Acute Toxicity Category 5 (GHS 2017), or unclassified (Regulation (EC) No 1272/2008).
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
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)
Version / remarks:
adopted in 1987
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Remarks:
Certifying authority: Niedersächsisches Umweltministerium, Hannover, Germany
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Hsd/Cpb:WU
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Fa. Harlan Winkelmann GmbH, Borchen, Germany
- Age at study initiation: not reported
- Weight at study initiation: males: 213 - 234 g; females: 170 - 206 g
- Housing: collective housing up to a maximum of 5 animals per Makrolon type III cage. Sterililzed Lignocel (J. Rettenmaier & Söhne GmbH +Co, Ellwangen-Holzmühle, Germany) bedding was provided.
- Diet: pelleted rodent diet (Ssniff Spezialdiäten GmbH, Soest, Germany): ad libitum
- Water: drinking water as for human consumption; available from drinking bottles ad libitum
- Acclimation period: 15 days (range-finding), 28 days (main test, females), or 13 days (main test, males)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70 %
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): artificial lightning (120 lux) from 7 am - 7 pm
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.90 mL/kg

DOSAGE PREPARATION: Test substance administered undiluted.
Doses:
2000 mg/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: days 0 (immediately before treatment), 7 and 14 post-administration
- Necropsy of survivors performed: yes, 14 days post-administration. Animals were sacrificed by CO2 asphyxiation.
- Clinical signs including body weight: yes, at regular intervals during the 14-day observation period. Clinical signs were evaluated according to a modified Irwin-Screening procedure. The animals were examined at the following post-treatment intervals: 10 min, 1 h, 2h, 6h, 24h and thereafter once daily up to day 14.
Statistics:
No information provided.
Preliminary study:
A preliminary range finding test with a dose of 2000 mg/kg bw was conducted in two female rats. There were no deaths in the preliminary study.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 540 mg/kg bw
Based on:
act. ingr.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortality occurred.
Clinical signs:
other:
Body weight:
lower than 10% body weight loss
Remarks:
Weight gains were normal in all animals apart from the reduced weight gain in one female on day 14 post-administration.
Gross pathology:
Gross pathological examinations at 14 days post-administration (terminal necropsy) revealed no test article-dependent findings. The macroscopic change that was observed was attributable to minor variations which can occur spontaneously in rats of this strain and age.
Interpretation of results:
other: CLP criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study compliant with GLP and according to OECD test guideline 401 (adopted in 1987, deleted in 2002), the test substance did not lead to mortality in Wistar rats when administered at a dose of 2000 mg/kg bw (or 540 mg a.i./kg bw) orally via gavage. No clinical signs, macroscopic findings or effects on body weight were observed. Based on the results of this study, the LD50 for the test substance was considered to be > 540 mg/kg bw/day. Due to the experimental set-up, this result can be interpreted as either Acute Toxicity Category 5 (GHS 2017), or unclassified (Regulation (EC) No 1272/2008).
Endpoint:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Justification for type of information:
Please refer to the category justification provided in the category object.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Read-across based on all available data on acute oral toxicity in the Alkyl Ether Sulfates (AES) category.

For a detailed assessment of the acute oral toxicity of the Alkyl Ether Sulfates (AES) category, please refer to the category justification attached to the category object.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
Applying read-across based on grouping of substances (category approach), an oral LD50 > 2000 mg/kg bw is predicted for the target substance.
Executive summary:

The available data on acute oral toxicity in the Alkyl Ether Sulfates (AES) category reveal an oral LD50 value > 2000 mg/kg bw. Based on the category approach, an oral LD50 value > 2000 mg/kg bw is predicted for the target substance. As explained in the category justification, the differences in molecular structure and composition between the target substance and the members of the AES category are unlikely to lead to differences in the toxicological properties with respect to acute oral toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
The available information comprises adequate and reliable (Klimisch score 1 and 2) studies from various source substances in the Alkyl Ether Sulfates (AES) category with similar structures and intrinsic properties, incl. the registered substance. Read-across is justified based on common toxicokinetic behaviour and consistent trends in environmental fate, ecotoxicological and toxicological properties of the category member substances. The database of the AES category is thus sufficient to fulfil the standard information requirements set out in Annex VII, Section 8.5, in accordance with Annex XI, Section 1.5, of the REACH Regulation (EC) No. 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Occlusive dressing.
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:
According to Guideline.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 540 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortality occurred.
Clinical signs:
other: No systemic effects.
Gross pathology:
No effects.
Interpretation of results:
other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute dermal toxicity study in rats compliant with OECD TG 402 with deviations, the test substance did not induce mortality when animals were exposed to 2000 mg/kg bw test substance (or 540 mg a.i./kg bw) dermally, covered by an occlusive dressing, for 24 h. Therefore, the LD50 of the test substance was set to > 2000 mg/kg bw (or > 540 mg a.i./kg bw) in male and female rats. Due to the experimental set-up, this result can be interpreted as either Acute Toxicity Category 5 (GHS 2017), or unclassified (Regulation (EC) No 1272/2008).
Endpoint:
acute toxicity: dermal
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Justification for type of information:
Please refer to the category justification provided in the category object.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Read-across based on all available data on acute dermal toxicity in the Alkyl Ether Sulfates (AES) category.

For a detailed assessment of the acute dermal toxicity of the Alkyl Ether Sulfates (AES) category, please refer to the category justification attached to the category object.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
Applying read-across based on grouping of substances (category approach), a dermal LD50 > 2000 mg/kg bw is predicted for the target substance.
Executive summary:

The available data on acute dermal toxicity in the Alkyl Ether Sulfates (AES) category reveal a dermal LD50 value > 2000 mg/kg bw. Based on the category approach, a dermal LD50 value > 2000 mg/kg bw is predicted for the target substance. As explained in the category justification, the differences in molecular structure and composition between the target substance and the members of the AES category are unlikely to lead to differences in the toxicological properties with respect to acute dermal toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
The available information comprises adequate and reliable (Klimisch score 1 and 2) studies from various source substances in the Alkyl Ether Sulfates (AES) category with similar structures and intrinsic properties, incl. the registered substance. Read-across is justified based on common toxicokinetic behaviour and consistent trends in environmental fate, ecotoxicological and toxicological properties of the category member substances. The database of the AES category is thus sufficient to fulfil the standard information requirements set out in Annex VVII, Section 8.5, in accordance with Annex XI, Section 1.5, of the REACH Regulation (EC) No. 1907/2006.

Additional information

Acute oral toxicity


Data on acute oral toxicity are available for alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) as well as several member substances of the Alkyl Ether Sulfates (AES) category.


There are six studies investigating the acute oral toxicity of alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) all of which exhibit minor or major deficiencies when compared to the requirements of the latest OECD testing guidelines. However, none of the deviations renders the use of a study impossible. Therefore, all studies are accounted for in a Weight-of-Evidence approach. Since there are acute oral toxicity studies available also for several other members of the AES category, the studies with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) are also used to assess the endpoint for the complete category, i.e. for those AES substances lacking own data with respect to acute oral toxicity. Due to the high number of studies with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8), these data are not discussed in detail here. Instead, the discussion of acute oral toxicity based on all available studies in the AES category, incl. those with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) is provided.


 


Studies on acute oral toxicity, incl. those with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8), are available for the following AES substances:


 


Table 1: Database on acute oral toxicity in the Alkyl Ether Sulfates (AES) category





































































































CAS No. / EC No.



Substance



Study or Report No.



Study protocol



LD50 [mg /kg bw]



‘Linear’ subgroup



1471312-55-6 / 939-523-2



Alcohols, C8-10, ethoxylated, sulfates, sodium salts



121485



OECD 423 (2001)



> 2000



68585-34-2 / 500-223-8



Alcohols C10-16, ethoxylated (1-2,5 EO) sulphated, sodium salts



82-003D



Similar OECD 401



> 1250#



82-003A



Similar OECD 401



> 1250#



4302



OECD 401



> 2468# (f), >2479# (m)



4305



OECD 401



> 2366# (f), >2399# (m)



160-7904



--



> 2500#



68891-38-3 / 500-234-8



Alcohols, C12-14, ethoxylated, sulfates, sodium salts



R9501026



OECD 401



> 540#



2975



OECD 401



> 1750#



86630D/UGF 16/AC



OECD 401



> 2870#



88.2109



OECD 401



> 540#



158-7904



--



> 2700#



88.0678



OECD 401



> 1380#



174450-50-1 / 605-725-1



Alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts



2395



OECD 401 (1992)



> 2000



Mixed branched & linear’ subgroup



160901-28-0 / 500-465-4



Alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts



96-7701



Similar OECD 401



> 1500#



#: Adjusted for active ingredient (a.i.) content of the test material


 


Evaluation of acute oral toxicity as observed in studies


The concentration of AES substances in the test materials used in the acute oral toxicity studies, i.e., the so-called active ingredient (a.i.) content, varies from 24.34% to 98.70% with water being the solvent in most studies, if a solvent was used at all. Tested AES substances induced no or only mild clinical symptoms (e.g. increased/decreased activity, piloerection/hunched posture, diarrhoea, salivation, central nervous system depression) and had no effect on body weights or gross pathology. These clinical symptoms observed in some studies were transient in nature and resolved within a maximum of 3 days post-administration. More severe clinical symptoms were noted in one study (study no. 86630D/UGF 16/AC conducted with alcohols, C12-14, ethoxylated, sulfates, sodium salts, CAS No. 68891-38-3, EC No. 500-234-8), which included abnormal gait, decreased respiratory rate, ptosis, and pallor of extremities additionally to the symptoms mentioned above, at a dose of ≥ 3200 mg/kg bw (corresponding to ≥ 2240 mg a.i./kg bw). This dose, however, well exceeds the limit dose of 2000 mg/kg bw recommended for acute oral toxicity studies and relevant for the hazard assessment and to decide on classification and labelling. In the same study, one female at the 4000 mg/kg bw (equivalent to 2800 mg a.i./kg bw) dose also presented with low body weight gain between Days 8 -15, and the dose of 4100 mg/kg bw (corresponding to 2870 mg a.i./kg bw) was lethal in male and female rats. In another study (study no. 69-7701 conducted with alcohols, C9-11, branched and linear, ethoxylated, sulfates, sodium salts, CAS No. 160901-28-0, EC No. 500-465-4) one incidence of mortality without previously evident clinical symptoms occurred at the dose of 5100 mg/kg bw (corresponding to 1530 mg a.i./kg bw), 9 Days after dosing. In contrast, in all other 12 acute oral toxicity studies, no mortality occurred at any of the doses tested, which included doses up to 2870 mg a.i./kg bw. The reason for the deviation of the two studies from the non-toxicity observed in the other studies remains unclear. However, both studies are not the main contributors to the overall hazard conclusion.


In conclusion, the qualitative WoE analysis based on the available studies indicates that acute oral toxicity is not identified for most AES category members. The substances generally exhibit no potential to induce acute oral toxicity, reflected by an oral LD50 value of > 2000 mg/kg bw. The outcome of this overall WoE evaluation is used for the hazard assessment and to conclude on classification and labelling for all AES substances in the category. This evaluation is considered sufficient for the hazard assessment and classification and labelling of the AES substances. For a detailed evaluation of the acute oral toxicity of the substances in the AES category, please refer to the category justification attached to the category object.


 


Acute dermal toxicity


Data on acute dermal toxicity are available for alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) as well as several member substances of the Alkyl Ether Sulfates (AES) category.


There is a study investigating the acute dermal toxicity of alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) available. The study exhibits deficiencies when compared to the requirements of the latest OECD testing guidelines. However, the deviations do not render the use of the study impossible, and therefore, the study was evaluated as Klimisch 2.  Since there are acute dermal toxicity studies available also for several other members of the AES category, the study with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) is used to assess the endpoint for the complete category in a Weight-of-Evidence approach. Therefore, a discussion of acute dermal toxicity based on all available studies in the AES category, incl. that with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) is provided.


 


Studies on acute dermal toxicity, incl. that with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8), are available for the following AES substances:


 


Table 2: Database on acute dermal toxicity in the Alkyl Ether Sulfates (AES) category





































CAS No. / EC No.



Substance



Study or Report No.



Study protocol (adopted in)



LD50 [mg/kg bw]



‘Linear’ subgroup



1471312-55-6 / 939-523-2



Alcohols, C8-10, ethoxylated, sulfates, sodium salts



121486



OECD 402



> 2000



68891-38-3 / 500-234-8



Alcohols, C12-14, ethoxylated, sulfates, sodium salts



R9600429



OECD 402



> 540#



174450-50-1 / 605-725-1



Alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts



2396



OECD 402



> 2000



#: Adjusted for active ingredient (a.i.) content of the test material


 


Evaluation of acute dermal toxicity as observed in studies


The first study was conducted with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2) in accordance with OECD guideline 402 and GLP compliant, as a limit test at 2000 mg/kg bw on five Wistar rats per sex. The pure test substance was applied for 24 h under semi-occlusive conditions. No mortalities and no clinical signs of toxicity were observed. Body weight change was not toxicologically relevantly affected at the end of the 14-day observation period. Moreover, no gross necropsy findings were observed. Overall, no signs of systemic toxicity were identified; but signs of local dermal irritation were reported. Slight erythema was observed on Day 4, which was fully reversed on Day 5, on all animals. Eschar formation was observed from Day 4 to Day 8 and desquamation was observed beginning on Day 6 in all animals. Desquamation was observed in most animals (7/10) until study termination. Scratches were observed on 2/5 females. The LD50 value was determined to be > 2000 mg/kg bw. The second study was conducted with alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts (CAS No. 174450-50-1, EC No. 605-725-1) in accordance with OECD guideline 402 and GLP compliant. For the limit test, the test substance (analytical purity 83.8%) was applied at 2000 mg/kg bw for 24 h under semi-occlusive conditions to five male and five female Wistar rats. No mortalities and no clinical signs of toxicity were observed. Body weight change was not toxicologically relevantly affected at the end of the 14-day observation period. Moreover, no gross necropsy findings were observed. Findings in this study were limited to local effects. Signs of dermal irritation at the application site were reported. The LD50 value was established at > 2000 mg/kg bw based on the test material used. The third available study conducted with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) as limit test in accordance with OECD guideline 402 and in compliance with GLP requirements. The test substance (analytical purity 27%) was applied at 2000 mg/kg bw for 24 h under occlusive conditions to five male and five female Wistar rats. No mortalities and no clinical signs of toxicity were reported. An LD50 value of > 2000 mg/kg bw, based on the test material used, was found. Considering the given concentration of the substance (i.e. a.i. content) in the test material used, the calculated LD50 value is > 540 mg a.i./kg bw.


The available studies are assessed in a WoE approach. The analysis indicates a very low potential of AES category member substances to induce acute dermal toxicity. Since the only effects observed in the studies are related to skin irritation, a dermal LD50 value of > 2000 mg/kg bw is considered for the hazard assessment and to conclude on the classification and labelling of all AES category member substances. This evaluation is considered sufficient for the hazard assessment and classification and labelling of the AES substances. For a detailed evaluation of the acute dermal toxicity of the substances in the AES category, please refer to the category justification attached to the category object.


 


Data on counter ions


An excessive database of human health-related information is available for sodium and magnesium cations (Na+ and Mg2+, respectively), e.g. assessments of dietary reference values, evaluation of mineral requirements of humans, and reviews of cosmetic ingredients. Both cations are not associated with acute toxic effects. In animal studies on rats and mice (oral) and rabbits (dermal), oral LD50 values of > 3000 mg/kg bw and dermal LD50 values as high as > 10000 mg/kg bw were found for sodium chloride. Mg2+ is used in cosmetics, both leave-on and rinse-off, and magnesium sulfate and stearate concentrations of 11% and 25%, respectively, can be safely used.


There is a substantial data base on ammonium sulfate available. It is not listed in Annex VI of the CLP Regulation (EC) No. 1272/2008. Ammonium sulfate gives no rise to concern of adverse effects on human health. In addition, an oral LD50 value for ammonium chloride of 1650 mg/kg bw is reported by EFSA. In summary, a contribution of the ammonium cation (NH4+) to the toxicity profiles of the relevant AES substances is not expected.


Studies on acute oral and dermal toxicity performed with the AES member substance alcohols C12-14 (even numbered), ethoxylated (< 2.5 EO), sulphated, triisopropanolamine salts (CAS No. 174450-50-1, EC No. 605-725-1) resulted in LD values of > 2000 mg/kg bw for both exposure routes. This indicates that triisopropanolamine (TIPA) will not have an effect on the prediction of acute toxicity for AES member substances lacking own data.


For a detailed evaluation of a potential effect of the counter ions on the toxicological profiles of the AES member substances, please refer to the category justification attached to the category object.

Justification for classification or non-classification

The available data on acute oral and dermal toxicity obtained with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS No. 68891-38-3, EC No. 500-234-8) as well as with members of the Alkyl Ether Sulfates (AES) category do not meet the criteria for classification according to the CLP Regulation (EC) No. 1272/2008 and are therefore conclusive but not sufficient for classification.


 


Regarding acute toxicity via the inhalation route of exposure, no information is required according to the REACH Regulation (EC) No. 1907/2006, Annex VIII, Section 8.5, Column 2, as data on acute oral and acute dermal toxicity are provided.