Sulfuric acid, C12-14 (even numbered)-alkyl esters, (2-hydroxylpropyl)ammonium salts

Endpoint summary

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

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 are no data on acute oral and dermal toxicity available for C12-14 AS MIPA (CAS 85681-66-9). Therefore these endpoints are covered by read-across to structurally related alkyl sulfates (AS), i.e. C12-14 AS Na (CAS 85586-07-8), C10-16 AS Na (CAS 68585-47-7), C12 AS Na (CAS 151-21-3) and C12-13 AS Na (CAS 91783-23-2) for acute oral toxicity and C10-16 AS NH4 (CAS 68081-96-9), C10-16 AS Mg (CAS 68081-97-0), C12-13 AS K (CAS 91783-22-1) and C8 AS 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. Therefore, the AS of the AS category have similar physicochemical, 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.

 

Acute oral toxicity

There is one relevant study for C12-14 AS Na (CAS 85586-07-8) and three studies for the C10-16 AS Na (CAS 68585-47-7), C12 AS Na (CAS 151-21-3) and C12-13 AS Na (CAS 91783-23-2) each addressing acute oral toxicity available.

The key study conducted with C12-14 AS Na (CAS 85586-07-8), was performed similar to OECD Guideline 420 on Wistar rats (KAO, 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 observed 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 showed 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.

The study conducted with C10-16 AS Na (CAS 68585-47-7, analytical purity 85%) was performed similar to OECD Guideline 401 (Huntsman, 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 C12 AS Na (CAS 151-21-3, analytical purity 98%) similar to OECD Guideline 401 with acceptable restrictions on Wistar rats (BASF, 1983). Both sexes were dosed with the test substance via gavage. Mortalities occurred but no 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 in animals sacrificed upon study termination. The LD50 was given as 1200 mg/kg bw for males and females, 977 mg/kg bw for females and 1427 mg/kg for males. 

A further study performed similar to OECD Guideline 401 was conducted with C12-13 AS 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 a fixed 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 C12-14 AS Na (KAO, 1994). The LD50 for C12 AS in a study with 98% active ingredient was 1200 mg/kg bw (BASF, 1983) for males and females. The LD50 for C12-13 AS was in a comparable dose range (Sasol, 1984). Both substances are more toxic than C12-14 AS Na and hence represent a worst-case. Moreover, taking into account that the study with 85% active ingredient of C10-16 AS resulted in a LD50 of greater than 2000 mg/kg bw (Huntsman, 1978), the adjusted LD50 for C12-14 AS (100%) would be 1800 mg/kg bw.

Based on the results mentioned above, a LD50 of 1800 mg/kg bw is justified for C12-14 AS MIPA (CAS 85681-66-9). Therefore, the available data on acute oral toxicity meet the criteria for classification as Acute Tox Cat 4 (H302) according to Regulation (EC) 1272/2008.

 

Acute dermal toxicity

Regarding the acute dermal toxicity four studies are available for the read-across substances C10-16 AS NH4 (CAS 68081-96-9), C10-16 AS Mg (CAS 68081-97-0), C12-13 AS K (CAS 91783-22-1) and C8 AS Na (CAS 142-31-4).

The key study was conducted with C8 AS 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 study conducted with C10-16 AS NH4 (CAS 68081-96-9) was performed as limit test conducted similar to OECD Guideline 402 with Three male and three female New Zealand White rabbits (P&G, 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 severe erythema and slight eschar formation at 24 h, necrosis on Days 2–14 with sloughing of the skin on Days 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 C10-16 AS Mg (CAS 68081-97-0) was performed as limit test conducted similar to OECD Guideline 402 with three male and three female New Zealand White rabbits (P&G, 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 severe erythema and eschar formation at 24 h, necrosis by Days 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 C12-13 AS K (CAS 91783-22-1) on three male and three female New Zealand White rabbits (P&G, 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.

Acute inhalation toxicity

No studies for acute inhalation toxicity are available. However, testing the potential of acute toxicity via inhalation route of C12-14 AS MIPA (CAS 85681-66-9) 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 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.

 

Acute toxicity of counter-ions

The effects on health of isopropanolamine (MIPA) are dominated by its corrosive properties. MIPA is listed in Annex VI of EG 1272/2008 as Skin Corrosive Category 1B, H314. Further information indicates MIPA to be moderately toxic after dermal application. During the registration process for 2010 MIPA was also classified as harmful in contact with skin (Acute Toxicity Cat 4, H312 according to Regulation 1272/2008/EC). This self-classification was 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. 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 doses of 630 and 1300 mg/kg, anorexia was observed, and at a dose of 1300 mg/kg, diarrhea was observed. Upon necropsy at the end of a 2-week observation period, no treatment-related changes were noted. No details on exposure conditions are available. With regard to the endpoint acute dermal toxicity, MIPA is not expected to increase the toxicity of C12-14 AS MIPA (CAS 85681-66-9) upon topical application significantly. Hydrolysis or dissociation of C12-14 AS MIPA (CAS 85681-66-9) will yield in one moiety of MIPA and one moiety of the alkyl sulfate.

Corrected for the molecular weights (MIPA: 75 g/mol, C12-14 AS: approx. 281 g/mol, C12-14 AS MIPA: approx. 356 g/mol) the LD50 value for MIPA applied as C12-14 AS MIPA is approximately 8800 mg/kg bw. Thus a contribution of MIPA to the dermal toxicity (if any) is negligible.

 

[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 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. The available data on acute dermal toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification. 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) in case the substance is available as neat powder.