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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Oral


LD50 (rat, f) > 2000 mg/kg bw (OECD 423, GLP)


Conclusion based on data with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2).


 


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 (rat, m/f) > 2000 mg/kg bw (OECD 402, GLP)


Conclusion based on data with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 Aug - 19 Sep 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted in 2001
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: WISTAR rats Crl: WI(Han)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 8-9 weeks
- Weight at study initiation: Step 1 (animals 1-3): 159 - 166 g; Step 2 (animals 4-6): 152 - 155 g
- Fasting period before study: Food was withheld from the test animals for 16 to 19 hours prior to the administration.
- Diet (ad libitum): Altromin 1324 maintenance diet for rats and mice (lot no. 0856)
- Water (ad libitum): tap water, sulphur acidified to a pH value of approximately 2.8
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200g/L

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 females per step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A careful clinical examination was made several times on the day of dosing. Thereafter, the animals were observed for clinical signs once daily. The animals were weighed on day 1 (prior to the application) and on days 8 and 15.
- Necropsy of survivors performed: yes
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured.
Clinical signs:
other: Clinical signs within the first 3 days after application comprised among others of piloerection, half eyelid-closure, tremor, reduced spontaneous activity, catalepsis and kyphosis. No clinical signs were observed thereafter.
Body weight:
lower than 10% body weight loss
Remarks:
Body weight gain was unaffected by treatment.
Gross pathology:
No findings upon necropsy.
Interpretation of results:
other: CLP criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
The present experiment was conducted according to OECD test guideline 423 and compliant with GLP. Under the conditions of the study, the acute oral median lethal dose (LD50) of the test substance was found to be > 2000 mg/kg bw. Due to the experimental set-up, this result can be interpreted either a sAcute Toxicity Category 5 (GHS 2017), or unclassified (Regulation (EC) No. 1272/2008).
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 an adequate and reliable (Klimisch score 1) study performed with the registered substance. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, Item 8.5, of 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
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 Aug - 27 Aug 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted in 1987
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Crl:WI(Han)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: males: 7 - 8 weeks, females: 11 - 12 weeks
- Body weight at study initiation: males: 221 – 235 g, females: 212 – 229 g.
- Diet (ad libitum): Altromin 1324 maintenance diet for rats and mice (lot no. 0939)
- Water (ad libitum): tap water, sulphur acidified to a pH value of approximately 2.8
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: approx. 10%
REMOVAL OF TEST SUBSTANCE
- Washing: The residual test item was removed using aqua ad injectionem
- Time after start of exposure: 24 h
Duration of exposure:
24 h
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: A careful clinical examination was made several times on the day of dosing. Thereafter, the animals were observed for clinical signs once daily. The animals were weighed on Day 1 (prior to the application) and on Days 8 and 15.
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Mortality:
No mortality occured.
Clinical signs:
other: No clinical signs of toxicity occurred.
Body weight:
lower than 10% body weight loss
Remarks:
For details, please refer to Table 1 under "Any other information on results incl. tables".
Gross pathology:
Upon gross pathology hernia (liver) into the diaphragm was observed in one female. This incidental finding is not considered to be treatment related.
Other findings:
Signs of irritation:
Erythema grade 1 as well as eschar and desquamation were observed in 10/10 animals. Scratches were observed in 2/5 females. In 3/5 males and 4/5 females, all signs of irritation were not reversible within the observation period.

Table 1: Absolute Body Weights in g and Body Weight Gain in %

Animal No. / Sex

Day 1

Day 8

Day 15

Day 1-15

21 / male

226 g

241 g

282 g

25 %

22 / male

231 g

250 g

292 g

26 %

23 / male

230 g

238 g

274 g

19 %

24 / male

221 g

236 g

270 g

22 %

25 / male

235 g

245 g

282 g

20 %

Mean ± SD

229 ± 5.3 g

242 ± 5.6 g

280 ± 8.5 g

22 ± 3.0 %

26 / female

213 g

215 g

220 g

3 %

27 / female

216 g

213 g

217 g

0 %

28 / female

212 g

205 g

216 g

2 %

29 / female

229 g

227 g

250 g

9 %

30 / female

217 g

223 g

234 g

8 %

Mean ± SD

217 ± 6.8 g

217 ± 8.6 g

227 ± 14.6 g

4 ± 3.9 %

Interpretation of results:
other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
This study was performed according to OECD test guideline 402 and compliant with GLP. Under the conditions of this limit test, the median lethal dose (LD50) of the test item (technical substance) after a single 24-h dermal administration was found to be greater than 2000 mg/kg bw in male and female Crl:WI Wistar rats. It is concluded that the CLP/ EU GHS criteria are not met and that no classification is required according to Regulation (EC) No 1272/2008.
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 an adequate and reliable (Klimisch score 1) study performed with the registered substance. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, Item 8.5, of Regulation (EC) No. 1907/2006.

Additional information

Acute oral toxicity


Data on acute oral toxicity are available for alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2) as well as several member substances of the Alkyl Ether Sulfates (AES) category.


 


Study with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2)


A study to investigate the acute oral toxicity of alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2) was performed, according to OECD guideline 423 (2001) and compliant with GLP, with 6 female Wistar rats in two steps (Z&S, 2012a). Per step, 3 animals received 2000 mg/kg bw test substance via oral gavage. The animals were observed daily for clinical signs of toxicity. Body weight was assessed before treatment and on Days 8 and 15. Upon study termination, animals were sacrificed, and gross pathology was performed. No mortality occurred. Clinical signs of toxicity within the first 3 days after application were observed and comprised of, inter alia, piloerection, half eyelid-closure, tremor, reduced spontaneous activity, catalepsy, and kyphosis. No clinical signs were observed thereafter. No effects on body weight and upon necropsy occurred. Thus, the LD50 was determined to be > 2000 mg/kg bw.


 


Studies in the AES category


Additional studies on acute oral toxicity 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



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, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2) as well as several member substances of the Alkyl Ether Sulfates (AES) category.


 


Study with alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2)


The acute dermal toxicity of alcohols, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2) was tested in a study according to OECD guideline 402 (Z&S, 2012b). The test substance was applied at a dose of 2000 mg/kg bw for 24 h under semi-occlusive conditions. Residual test substance was removed after the exposure period and the animals were observed for clinical signs of toxicity daily. Body weight was assessed before treatment and on Days 8 and 15. Upon study termination animals were sacrificed and gross pathology was performed. In addition, signs of erythema and oedema were assessed using the scoring system laid down in OECD guideline 404 (Testing of acute dermal irritation / corrosion). No mortality and no clinical signs of toxicity occurred. Signs of dermal irritation were observed. Erythema grade 1 was observed on 10/10 animals on Day 4 which was fully reversed on Day 5 in all animals. Eschar formation was observed from Day 4 to Day 8 and desquamation was observed beginning on Day 6 (10/10 animals both). Desquamation was observed in 7/10 animals until study termination. Scratches were observed in 2/ 5 females. Effects on body weight were seen for females but were considered to be of no toxicological relevance. Moreover, hernia of the liver as an incidental finding was found upon gross pathology. The LD50 for acute dermal toxicity was determined to be > 2000 mg/kg bw.


 


Studies in the AES category


Additional studies on skin irritation / corrosion 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



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


A 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.


Another available study was 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, C8-10, ethoxylated, sulfates, sodium salts (CAS No. 1471312-55-6, EC No. 939-523-2) 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.