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Description of key information

Oral LD50 (OECD guideline 401), rat = 1800 mg/kg bw
Dermal LD50 (OECD guideline 402), rabbit > 2000 mg/kg bw (limit test)
Acute toxicity by inhalation was not tested according to REGULATION (EC) No 1907/2006, Annex VIII, Section 8.5, Column 2.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 800 mg/kg bw
Quality of whole database:
The whole data base is conclusive and of high quality.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Acute toxicity by inhalation was not tested according to REGULATION (EC) No 1907/2006, Annex VIII, Section 8.5, Column 2.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The whole data base is conclusive and of high quality.

Additional information

There is only one study on the acute toxicity for C12-14AS TEA (CAS 90583-18-9) available. Therefore the endpoint acute toxicity is covered by read across to structurally related alkyl sulfates (AS), i.e. C12-14AS Na (CAS 85586-07-8), C10-16AS Na (CAS 68585-47-7), C12AS Na (CAS 151-21-3) and C12-13AS Na (CAS 91783-23-2) for acute oral toxicity and C10-16AS NH4 (CAS 68081-96-9), C10-16AS Mg (CAS 68081-97-0), C12-13AS K (CAS 91783-22-1) and C8AS Na (CAS 142-31-4) for the dermal route.The possibility of a read-across to other alkyl sulfates in accordance with Regulation (EC) No 1907/2006 Annex XI 1.5. Grouping of substances and read-across approach was assessed. In Annex XI 1.5 it is given that a read-across approach is possible for substances, whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity. The AS reported within the AS category show structural similarity. The most important common structural feature of the category members is the presence of a predominantly linear aliphatic hydrocarbon chain with a polar sulfate group, neutralized with a counter ion.. This structural feature confers the surfactant properties of the alkyl sulfates. The surfactant property of the members of the AS category in turn represent the predominant attribute in mediating effects on mammalian health.The AS of the AS category also have similar physico-chemical, environmental and toxicological properties, validating the read across approach within the category. The approach of grouping different AS for the evaluation of their effects on human health and the environment was also made by the OECD in the SIDS initial assessment profile [1] and by a voluntary industry programme carrying out Human and Environmental Risk Assessments (HERA [2]), further supporting the read across approach between structurally related AS.

There is a substantial data base on triethanolamine (TEA) online available. TEA is not listed in Annex VI of directive 1272/2008. In addition the effects of TEA on human health were assessed by the OECD in the SIDS initial assessment Report [3]. Despite of some local signs of irritation TEA gives no rise to concern of adverse effects on human health. Therefore a contribution of TEA to the effects on human health is considered to be negligible when assessing human health effects of C12-14AS TEA (CAS 90583-18-9). Therefore, read across to alkyl sulfates with other counter ions is considered to be valid and reliable. This approach was also followed by the OECD in the SIDS initial assessment profile [1] and by the voluntary industry programme carrying out Human and Environmental Risk Assessments (HERA [2]).

Acute oral toxicity 

There is one study for C12-14AS TEA (CAS 90583-18-9) and four relevant studies for the read-across substances C12-14AS Na (CAS 85586-07-8), C10-16AS Na (CAS 68585-47-7), C12AS Na (CAS 151-21-3) and C12-13AS Na (CAS 91783-23-2) addressing acute oral toxicity available.

Only limited information on test conditions and experimental methods are available for the study conducted with C12-14AS TEA (CAS 90583-18-9) itself. Groups of fasted male and female rats were administered a 20% aqueous solutions of the test item and observed for 10 days. The LD50 was found to be greater than 200 mg/kg bw based on active ingredient.

The key study conducted with C12-14AS Na (CAS 85586-07-8), was performed similar to OECD Guideline 420 on Wistar rats (Puig, 1994). Five Wistar rats of both sexes were dosed with the test substance at 500 and 2000 mg/kg bw via gavage. All males and one female of the top dose group died within 24 h after the application of the test substance. No clinical signs of toxicity were seen in animals of the low dose group. Clinical signs of toxicity at 2000 mg/kg comprised hunched back, decrease in motor activity, ataxia and pallor. In addition the males had piloerection and the females hypotonia. Upon necropsy haemoperitoneum, congested mucous membranes of the gastro-intestinal tract, and bloody looking liquid inside these organs occurred in one of the males which died during the course of the study. One female of the 2000 mg/kg bw dose group showed dilation of the small intestines and caecum. No further findings were observed upon necropsy. The LD50 was greater than 500 but below 2000 mg/kg bw.

A study conducted with C10-16AS Na (CAS 68585-47-7) was performed similar to OECD Guideline 401 (Cawley, 1978). Five Spraque-Dawley rats of each sex were dosed with the test substance at the limit dose of 2000 mg/kg bw via gavage and observed for mortality and clinical signs for 14 days. One female died after application of the test substance. No clinical signs of toxicity were seen in any animal. The LD50 was determined to be greater than 2000 mg/kg bw.

A further study was conducted with C12AS Na (CAS 151-21-3, analytical purity 30%) similar to OECD Guideline 401 (Esposito, 1976). Five Wistar rats of each sex were dosed with the test substance at the limit dose of 5000 mg/kg bw via gavage and observed for mortality and behaviour for 14 days. Mortalities occurred 24 hours (2/5 males) and 3 days after treatment (1/5 females). No reduced activity of animals was observed during the post exposure period. The LD50 was determined to be greater than 5000 mg/kg bw based on the test substance and greater than 1500 mg/kg bw based on the active ingredient.

A further study performed similar to OECD Guideline 401 was conducted with C12-13AS Na (CAS 91783-23-2, analytical purity 26.8%). Five Wistar rats of each sex were dosed with the test substance at 880, 1040, 1260 and 1500 mg/kg bw via gavage and observed for mortalities for 14 days (Sasol, 1984). At the lowest dose no mortalities occurred. In the 1040, 1260 and 1500 mg/kg bw dose groups 0/5, 3/5 and 5/5 males and 2/5, 5/5 and 5/5 females died within 14 days. No data on clinical signs of toxicity are available. The LD50 was determined to be 1230 mg/kg bw for males and 1063 mg/kg bw for females.

In the following afixed dose for the LD50-value is discussed. Looking at the acute oral toxicity of AS in rodents it can be seen that the toxicity decreases with increasing chain length (see Category Justification Report & HERA report). Evaluations of test materials comprising mixtures of chain lengths also showed a trend to lower toxicity as the proportion of longer chain lengths in the test material increases.

Using the OECD 420 fixed dose method no deaths at 500 mg/kg bw and 60% deaths at 2000 mg/kg bw occurred, resulting in a LD50 presumably greater than 1000 mg/kg bw for C12-14AS (Puig, 1994). This LD50 was evaluated as well for C12-13 (Sasol, 1984) which is more toxic than C12-14AS and hence represents a worst-case. Moreover, taking in account that the study with 85% active ingredient of C10-16AS resulted in a LD50 of greater than 2000 mg/kg bw, the adjusted LD50 for C12-14AS (100%) would be 1800 mg/kg bw (Cawley, 1978). This limit value is further supported by a study with 30% active ingredient on the more toxic C12AS (Esposito, 1976), providing a LD50 of greater than 5000 mg/kg bw, i.e. greater than 1500 mg/kg bw for 100% a.i.

Hence, a LD50 of 1800 mg/kg bw is justified for C12-14AS TEA (CAS 90583-18-9).

Acute dermal toxicity

Regarding the acute dermal toxicity four studies are available for the read-across substances C10-16AS NH4 (CAS 68081-96-9), C10-16AS Mg (CAS 68081-97-0), C12-13AS K (CAS 91783-22-1) and C8AS Na (CAS 142-31-4).

The key study was conducted with C8AS Na (CAS 142-31-4) according to OECD Guideline 402 (BASF, 2012). 5 Wistar rats per sex were trated with 2000 mg/kg bw under semi occlusive conditions for 24 h. No mortality occurred, no sign of systemic toxicity and of local irritation was observed.

The study conducted with C10-16AS NH4 (CAS 68081-96-9) was performed as limit test conducted similar to OECD Guideline 402 with 3 male and 3 female New Zealand White rabbits (Frank, 1975). The test substance (analytical purity 25.1%) was applied at 2000 mg/kg bw for 24 h under occlusive conditions. No mortalities occurred. Clinical signs of toxicity comprised severe erythema and slight eschar formation at 24 h, necrosis on day 2–14 with sloughing of the skin on day 8–14 and hyper-pigmentation of new skin by day 14. No signs of systemic toxicity were observed. Hence, the LD50 value is greater than 2000 mg/kg bw based on the test material and greater than 500 mg/kg bw based on active ingredient.

The study conducted with C10-16AS Mg (CAS 68081-97-0) was performed as limit test conducted similar to OECD Guideline 402 with 3 male and 3 female New Zealand White rabbits (Frank, 1975). The test substance (analytical purity 23.5%) was applied at 2000 mg/kg bw for 24 h under occlusive conditions. No mortalities occurred. Clinical signs of toxicity comprised severe erythema and eschar formation at 24 h, necrosis by Day 5–21 and necrotic tissues sloughed and leaving skin hyper-pigmented at Day 21. Hence, the LD50 value is greater than 2000 mg/kg bw based on the test material and greater 500 mg/kg bw based on the active ingredient.

Another study similar to OECD Guideline 402 was performed with C12-13AS K (CAS 91783-22-1) on three male and three female New Zealand White rabbits (Benedict, 1978). Both sexes were dosed at 2000 mg/kg bw (analytical purity 25%) under occlusive conditions for 24 h. No mortalities occurred during the conduct of the study. Findings within this study comprised moderate to severe erythema, edema, and atonia, desquamation and fissuring by day 6 and eschar formation and exfoliation. Based on the above mentioned findings the LD50 was greater than 2000 mg/kg bw based on test material and greater 500 mg/kg bw based on active ingredient.

Within the studies mentioned above no mortalities or signs of systemic toxicity occurred after dermal application of alkyl sulfates with varying carbon chain length. Taken into account the generally low toxicity after oral application and the low dermal absorption rate of alkyl sulfates (approx. 1%) this result was expected. In agreement, no classification for acute dermal toxicity is required. For details on absorption please see section Toxicokinetics, metabolim and distribution.

Acute inhalation toxicity

No studies for acute inhalation toxicity are available. However, testing the potential of acute toxicity via inhalation route of C12-14AS TEA (CAS 90583-18-9) is considered to be not justified. According to Regulation (EC) No 1907/2006, Annex VIII, Section 8.5, Column 2, in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. As information under 8.5.3 (dermal route) is provided, the requirement is fulfilled by using the most appropriate route of exposure.

AS is mainly used in liquid media. Due to its very low vapour pressure [2], inhalation is not viewed as a significant route of exposure.Inhalation of AS may occur via aerosols generated by spray cleaners or by detergent dusts (e.g. washing powder). Taking into account that the acute toxicity of AS is generally low but that the substance is irritating to skin and eyes at concentrations of 10% or higher, no additional information is expected from testing for acute inhalation toxicity as the predominant effect will be local irritation rather than systemic toxicity. However, as the neat substance has to be classified as harmful if swallowed the substance will also be classified as harmful if inhaled (H332: Acute tox 4 and R20, respectively) in case the substance is available as neat powder.

 

[1] SIDS initial assessment profile, (2007);
http://www.aciscience.org/docs/Alkyl_Sulfates_Final_SIAP.pdf

[2] (HERA Draft report, 2002);
http://www.heraproject.com/files/3-HH-04-%20HERA%20AS%20HH%20web%20wd.pdf

[3] SIDS initial assessment report, (1995);

http://webnet.oecd.org/HPV/UI/SIDS_Details.aspx?Key=5ca67317-5fcc-41ea-a429-53d1267be383&idx=0


Justification for selection of acute toxicity – oral endpoint
Reliable OECD guideline study.

Justification for selection of acute toxicity – dermal endpoint
Reliable OECD guideline study.

Justification for classification or non-classification

The available data on acute oral toxicity meet the criteria for classification as Acute Toxicity Category 4 (H302) according to Regulation (EC) 1272/2008 and as Xn (R22) according to Directive 67/548/EEC. The available data on acute dermal toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

Exposure to solid C12-14AS TEA (CAS 90583-18-9) with a bulk density < 400g/L may occur. As worst case assumption this material is classified as Acute Toxicity Category 4 (H332) according to Regulation (EC) 1272/2008 and as Xn (R20) according to Directive 67/548/EEC.