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Description of key information

Oral LD50 (OECD guideline 401), rat = 1200 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
1 200 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
2 000 mg/kg bw
Quality of whole database:
The whole data base is conclusive and of high quality.

Additional information

There are two studies for the acute oral toxicity of C12AS Na (CAS 151-21-3) available. The available publication regarding the endpoint acute dermal toxicity of C12AS Na (CAS 151-21-3) is considered not sufficient for risk assessment. Therefore the endpoint acute dermal toxicity is covered by read across to structurally related alkyl sulfates, i.e. 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 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. Therefore, the AS of the AS category 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. A detailed justification for grouping of alkyl sulfates into a category is provided separately. Please refer for more details on the read-across also to the document “AS Category Approach Justification” attached in section 13 of IUCLID.

Acute oral toxicity

The acute oral toxicity key study conducted with C12AS Na (CAS 151-21-3) was performed according to OECD Guideline 401 with acceptable restrictions on Wistar rats (Potokar, 1983). Both sexes were dosed with the test substance via gavage. Mortalities occurred but no further details were available. Clinical signs of toxicity comprised diarrhoea, spastic gait, decreased activity, lateral position, hunched posture, laboured respiration and coma. Necropsy of dead animals revealed haemorrhages in gastro-intestinal tract and vascular congestion in the liver. No findings were observed at necropsy of the surviving animals at the end of the 14-day observation period. Based on statistical evaluation of the results, the LD50 was determined to be 977 mg/kg bw for females and 1427 mg/kg for males. The LD50 for males and females was 1200 mg/kg bw/d.

The second study conducted with C12AS Na (CAS 151-21-3, analytical purity 30%) was performed similar to OECD Guideline 401 (Esposito, 1976). 5 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 mortalities and behaviour for 14 days. Mortalities occurred 24 hours (2/5 males) and 3 days after treatment (1/5 females). No depression 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.

Thus, the LD50 of 1200 mg/kg bw observed for males and females by Potokar (1983) was chosen as a conservative approach.

Acute dermal toxicity

Regarding the acute dermal toxicity one study with C12AS Na (CAS 151-21-3) is available which however was not reliable for risk assessment due to reporting deficiencies. Therefore a read-across from 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) was performed.

One study with C12AS Na (CAS 151-21-3, 33% aqueous slurry) was performed with presumably 10 male rabbits per dose group. C12AS Na was applied at 150, 300, 600, 1200 or 2000 mg/kg bw for 24 h to intact and abraded skin (Carson and Oser, 1964). Animals were observed for clinical signs of toxicity and the body weights were recorded. Animals found dead and animals surviving until scheduled necropsy after the 14 d observation period were submitted to gross pathological examinations. Mortalities were 1/10, 2/10, 4/10, 8/10 and 10/10 animals in the 150, 300, 600, 1200 or 2000 mg/kg bw groups, respectively. Clinical signs includedtremors, tonic-clonic convulsions, and respiratory failure. Decreased body weights were reported during the 14 day observation period in animals of the 300 and 600 mg/kg bw group. No data for 1200 and 2000 mg/kg bw are provided. At necropsy, the treated skin area appeared leathery and showed scaling. The LD50was calculated to be 580 mg/kg bw (corresponding to about 200 mg active substance/kg bw). No information is given how many animals have been used with intact and with abraded skin and the stated results do not distinguish between animals with intact and abraded skin. Thus it is likely that the LD50 was calculated with data of animals with abraded and intact skin. Moreover it is not stated if more animals with abraded skin died or if they died earlier than animals with intact skin. The same holds true for other observations like tremor, convulsions or respiratory failure. Secondly, data on sex, strain, housing and feeding conditions of animals used in those experiments as well as necropsy data and details about the incubation method and the test item were not provided. Consequently the study was judged with Klimisch Code 4 (data not sufficient for risk assessment) since a number of data are missing to assess the toxic behaviour of the substance of concern on the intact skin. This conclusion is further supported by the calculated LD50 dermal (ca. 200 mg/kg active substance) which is much lower compared to the observed LD50 oral (1200 mg/kg) in the same species, although the oral absorption is assumed to be complete (100%) while dermal absorption is approximately 1% (refer to IUCLID section 7.1 Toxikokinetics, metabolism and distribution). Therefore a read-across to available acute dermal toxicity studies for risk assessment purposes was performed.

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 treated 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 supporting 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, 1975a). 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 of severe erythema and slight eschar formation at 24 h, necrosis by day 2–14 with sloughing of the skin by 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 the 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, 1975b). 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 of 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 of 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 is greater than 2000 mg/kg bw based on the test material and greater 500 mg/kg bw based on the active ingredient.

Conclusion

There was no evidence of systemic toxicity when AS were applied to intact skin, consistent with the fact that dermal penetration of the surfactants is low. Findings comprised local skin irritation, eschar formation and necrosis with sloughing. The key study with C8AS Na was performed according to OECD Guideline 402 and according to the principles of GLP. Neither systemic toxicity nor mortality was observed within this study. C8 and C12 alkyl sulfates are classified as skin irritants but there is evidence that the skin irritating potential of C12AS Na exceeds the one of C8AS Na (for details refer to endpoint summary of section irritation/corrosion). Therefore local skin effects after dermal application will presumably be more serious for C12AS Na but systemic toxicity of C12AS Na is not expected. This is supported byFrank (1975 a, b) and Benedict (1978) who reported signs of local irritation after dermal application of alkyl sulfates containing C12 carbon chains but no signs of systemic toxicity.Thus, the LD50 of alkyl sulfates is >2000 mg/kg bw.

Acute inhalation toxicity

No studies for acute inhalation toxicity are available. However, testing the potential of acute toxicity via inhalation route of C12AS Na (CAS 151-21-3) 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 and due to its very low vapour pressure [2] inhalation is not viewed as a significant route of exposure. Inhalation of AS may occur by inhalation of aerosols generated by spray cleaners or by inhalation of detergent dusts (e.g. washing powder). Taken into account that the acute toxicity of AS is generally low no further information on acute toxicity is expected by testing for acute inhalation toxicity as the predominant effect will comprise of local irritant effects rather than systemic toxicity.

 

[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


Justification for selection of acute toxicity – oral endpoint
Reliable Guideline study which is the basis for classification/LD50 setting

Justification for selection of acute toxicity – dermal endpoint
The key study with pure test item was chosen.

Justification for classification or non-classification

The available data on acute oral toxicity meet the criteria for classification as Acute Tox Cat 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.