2-Propanol, 1-amino-, compds. with polyethylene glycol hydrogen sulfate C12-14-alkyl ethers

Endpoint summary

Description of key information

Oral

LD50 > 2000 mg/kg bw

Read-across based on grouping of substances (category approach) considering all available data on acute oral toxicity in the Alkyl Ether Sulfates (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

Read-across based on grouping of substances (category approach) 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

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

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. 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

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

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. 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 VIII, Section 8.5, in accordance with Annex XI, Section 1.5, of the REACH Regulation (EC) No. 1907/2006.

Additional information

Acute oral toxicity

No data on acute oral toxicity are available for alcohols, C12-14 (even numbered), ethoxylated (<=2.5 moles EO), sulfated, monoisopropanolamine salt (CAS No. 1187742-72-8, EC No. 932-185-7). In order to assess acute oral toxicity, potential studies in the database of the Alkyl Ether Sulfates (AES) category are considered in a read-across approach. Studies investigating 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
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

No data on acute dermal toxicity are available for alcohols, C12-14 (even numbered), ethoxylated (<=2.5 moles EO), sulfated, monoisopropanolamine salt (CAS No. 1187742-72-8, EC No. 932-185-7). In order to assess acute dermal toxicity, studies in the database of the AES category are considered in a read-across approach. Studies investigating acute dermal toxicity 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, in 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 the counter ion monoisopropanolamine (MIPA)

Monoisopropanolamine (CAS No. 78-96-6, EC No. 201-162-7, 1-aminopropan-2-ol, MIPA) can either be contained in alcohols, C12-14 (even numbered), ethoxylated (<=2.5 moles EO), sulfated, monoisopropanolamine salt (CAS No. 1187742-72-8, EC No. 932-185-7) as ‘free’ (i.e. not reacted) amine constituent or be formed from its cationic form by deprotonation of the counter ion mono-(2-hydroxypropyl)ammonium. Therefore, its potential impact on the toxicological properties of the registered AES substance alcohols, C12-14 (even numbered), ethoxylated (<=2.5 moles EO), sulfated, monoisopropanolamine salt (CAS No. 1187742-72-8, EC No. 932-185-7) needs to be evaluated. Studies on acute oral and acute dermal toxicity of MIPA are provided in the technical dossier of alcohols, C12-14 (even numbered), ethoxylated (<=2.5 moles EO), sulfated, monoisopropanolamine salt (CAS No. 1187742-72-8, EC No. 932-185-7) by means of an analogue approach.

The acute oral toxicity of MIPA was tested in a study similar to OECD guideline 401 (BASF, 1965a). Groups consisting of 5 US-rats/sex/dose were treated by single gavage administration with an aqueous solution of the test substance at doses of 194, 1552, 1940, 2425, 3104, 6208 mg/kg bw. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 14 days, the surviving animals were sacrificed and necropsied. Animals that died during the observation period were also subjected to necropsy. Mortalities occurred as follows: 10/10, 7/10, 2/10, 1/10, 0/10, and 0/10 at 6208, 3104, 2425, 1940, 1557, and 194 mg/kg bw, respectively. Mortality occurred as early as 1 h and until 24 h after dosing. Clinical signs observed in the high- and middle-dose groups included restlessness, stagger, creep, slight abdominal position, anaemia, tonic-clonic convulsions, and mouth discharge. At all dose level compulsive chewing, dyspnoea and apathy were observed. Findings upon necropsy included red discoloration of abdominal viscus at 6208 and 3104 mg/kg bw, irritation of the bowel, and dilatation of the stomach at 2425 mg/kg bw, bronchitis and bronchiectasia at 1940 and 194 mg/kg bw. No abnormalities were noted at 1557 mg/kg bw. Based on the findings of this study, a LD50 for acute oral toxicity in male and female rats of 2813 mg/kg bw was established. Since the acute oral LD50 was established for all AES category member substances to be > 2000 mg/kg bw, MIPA is not expected to contribute to the acute oral toxicity of alcohols, C12-14 (even numbered), ethoxylated (<=2.5 moles EO), sulfated, monoisopropanolamine salt (CAS No. 1187742-72-8, EC No. 932-185-7).

According to the disseminated registration (ECHA, 2022) MIPA is classified, inter alia, as harmful in contact with skin (Acute Tox. 4, H312). The classification is based on a publication of Carreon and Yakel (1981), who reported a dermal LD50 value of 1851 mg/kg bw after dermal application of MIPA to rabbits, however, no details on exposure conditions are available. During the 14-day observation period, marked redness, moderate swelling, and marked necrosis of the skin were observed. Moreover, rabbits were lethargic at all doses (630 to 5000 mg/kg bw). At the doses of 630 and 1300 mg/kg, anorexia was observed, and at the dose of 1300 mg/kg, diarrhoea was observed. Upon necropsy at the end of a 14-day observation period, no treatment-related changes were noted. Regarding acute dermal toxicity, MIPA is not expected to increase the toxicity of alcohols, C12-14 (even numbered), ethoxylated (<=2.5 moles EO), sulfated, monoisopropanolamine salt (CAS No. 1187742-72-8, EC No. 932-185-7) in a significant way upon topical application. Hydrolysis or dissociation of the AES substance will produce one moiety of MIPA and one moiety of the alkyl ether sulfate. Corrected for the molecular weights (MIPA: 75 g/mol; alcohols, C12-14 (even numbered), ethoxylated (<=2.5 moles EO), sulfate: approx. 309 g/mol; alcohols, C12-14 (even numbered), ethoxylated (<=2.5 moles EO), sulfated, monoisopropanolamine salt: approx. 384 g/mol), the LD50 value for MIPA applied as alcohols, C12-14 (even numbered), ethoxylated (<=2.5 moles EO), sulfated, monoisopropanolamine salt (CAS No. 1187742-72-8, EC No. 932-185-7) is about 9500 mg/kg bw. Therefore, a contribution of MIPA to the dermal toxicity, if any, is considered to be negligible.

In conclusion, the available data on acute oral and dermal toxicity of MIPA indicate that the substance does not impact the toxicological properties of the registered AES substance alcohols, C12-14 (even numbered), ethoxylated (<=2.5 moles EO), sulfated, monoisopropanolamine salt (CAS No. 1187742-72-8, EC No. 932-185-7). For a detailed evaluation of the effect of MIPA and other counter ions on the toxicological profiles of the AES member substances, please refer to the category justification attached to the category object.

 

Carreon, R.E., and Yakel, H.O. (1981). Monoisopropanolamine: acute toxicological properties and industrial handling hazards. Unpublished, CTFA Code No. B-84–580, 28. 04. 1981. In: Beyer et al. (1987)

ECHA (2022). Disseminated registration dossier of 1-aminopropan-2-ol (CAS No. 78-96-6, EC No. 201-162-7), echa.europa.eu/registration-dossier/-/registered-dossier/13935 (last accessed 2022-10-27)

 

Data on other 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 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. Based on grouping of substances (category approach), alcohols, C12-14 (even numbered), ethoxylated (<=2.5 moles EO), sulfated, monoisopropanolamine salt (CAS No. 1187742-72-8, EC No. 932-185-7) is predicted not to fulfil the classification criteria and is consequently not classified for acute oral or dermal toxicity.

 

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.