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Administrative data

Description of key information

No data are available for the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2). Therefore, read-across from structural analogue substances has been applied.

Oral (EU Method B.1bis): LD50 (rat, m/f) > 500 <= 2000 mg/kg bw

Read-across from structural analogue source substance sulfuric acid, mono-C12-14-alkyl esters, sodium salts (CAS 85586-07-8), supported by additional studies with various structural analogue substances.

Acute toxicity by inhalation was not tested according to Regulation (EC) No. 1907/2006, Annex VIII, Section 8.5, Column 2.


Dermal (OECD 402): LD50 (rat, m/f) > 2000 mg/kg bw (limit test)

Read-across from structural analogue source substance sodium octyl sulfate (CAS 142-31-4), supported by additional studies with various structural analogue substances.

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 from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance.
Adequacy of study:
key study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 500 - <= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Source, key, 85586-07-8, 1994
Interpretation of results:
other: Acute tox. oral 4, H302. Classification according to Regulation (EC) No 1272/2008 (CLP/EU GHS)
Conclusions:
A LD50 range of > 500 <= 2000 mg/kg bw was determined in an experimental study investigating the acute oral toxicity of a structural analogue substance.
Executive summary:

The acute oral toxicity of the target substance is estimated based on an adequate and reliable in vivo study of a structural analogue source substance. A LD50 range of > 500 <= 2000 mg/kg bw was determined experimentally in male and female rats. Therefore, this LD50 range is applied for the hazard assessment and C&L purposes of the target substance. As explained in the category justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in the acute oral toxicity.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
The available information comprises adequate and reliable (Klimisch score 1 and 2) studies from various source substances with similar structures and intrinsic properties. Read-across is justified based on common physico-chemical, ecotoxicological and toxicological properties. The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, 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:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance.
Adequacy of study:
key study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Source, key, 142-31-4, 2012
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Conclusions:
A LD50 value of > 2000 mg/kg bw was determined in an experimental study investigating the acute dermal toxicity of a structural analogue substance.
Executive summary:

The acute dermal toxicity of the target substance is estimated based on an adequate and reliable in vivo study of a structural analogue source substance. A LD50 value of > 2000 mg/kg bw was determined experimentally and is also applied for the hazard assessment and C&L purposes of the target substance. As explained in the category justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in the acute dermal toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate and reliable (Klimisch score 1 and 2) studies from various source substances with similar structures and intrinsic properties. Read-across is justified based on common physico-chemical, ecotoxicological and toxicological properties. The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006.

Additional information

There are no data on acute oral and dermal toxicity available for the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2). Therefore, these endpoints are covered by read-across from structurally related alkyl sulfates (AS). The possibility of a read-across from 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 physico-chemical, 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, neutralised 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 represents the predominant attribute in mediating effects on mammalian health. Therefore, the members 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.

Ammonium sulfate is used to produce AS NH4 within the current AS category. There is a substantial data base on ammonium sulfate online available. Ammonium sulfate is not listed in Annex VI of Regulation (EC) No. 1272/2008 (CLP). In addition, the effects of ammonium sulfate on human health were assessed by the OECD in the SIDS initial assessment report [3]. Ammonium sulfate gives no rise to concern of adverse effects on human health. Therefore, a contribution of ammonium sulfate to the effects on human health is considered to be negligible when assessing human health effects of the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2).

 

Acute oral toxicity

Since no data on acute oral toxicity are available for the target substance, studies performed with the analogue substances sulfuric acid, mono-C12-14-alkyl esters, sodium salts (CAS 85586-07-8, key study), sodium tetradecyl sulfate (CAS 68585-47-7), sodium dodecyl sulfate (CAS 151-21-3), and sulfuric acid, mono-C12-13-alkyl esters, sodium salts (CAS 91783-23-2) have been considered.

The key study with sulfuric acid, mono-C12-14-alkyl esters, sodium salts (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 bw 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 sodium tetradecyl sulfate (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 sodium dodecyl sulfate (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 bw for males. 

Finally, a study performed similar to OECD Guideline 401 was conducted with sulfuric acid, mono-C12-13-alkyl esters, sodium salts (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.

The results of all four studies indicate a slight toxicity after oral administration. All LD50 values determined are in the range > 500 <= 2000 mg/kg bw and hence this range as obtained in the study Kao (1994) is considered the key result. It is taken forward to the hazard assessment and is used to determine the C&L of the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2).

 

Acute dermal toxicity

Regarding the acute dermal toxicity one key and three supporting studies are available for relevant read-across substances sodium octyl sulfate (CAS 142-31-4) (key study), sulfuric acid, mono-C10-16-alkyl esters, magnesium salts (CAS 68081-97-0), sulfuric acid, mono-C10-16-alkyl esters, ammonium salts (CAS 68081-96-9), and sulfuric acid, mono-C12-13-alkyl esters, potassium salts (CAS 91783-22-1).

The key study was conducted with sodium octyl sulfate (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. Since no mortalities occurred, the LD50 for male and female rats was considered to be > 2000 mg/kg bw.

A first supporting study conducted with sulfuric acid, mono-C10-16-alkyl esters, magnesium salts (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 (P&G, 1975a). 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.

The second supporting study conducted with sulfuric acid, mono-C10-16-alkyl esters, ammonium salts (CAS 68081-96-9) was again a limit test conducted similar to OECD Guideline 402 with 3 male and 3 female New Zealand White rabbits (P&G, 1975b). 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.

A further supporting study similar to OECD Guideline 402 was performed with sulfuric acid, mono-C12-13-alkyl esters, potassium salts (CAS 91783-22-1) on three male and three female New Zealand White rabbits (P&G, 1978a). 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.

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. No classification for acute dermal toxicity is required. For details on absorption please refer to section 7.1 Toxicokinetics, metabolism and distribution.

 

Acute inhalation toxicity

No studies for acute inhalation toxicity are available. However, testing the potential of acute toxicity via inhalation route of sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2) is considered to be not justified. According to the REACH 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 considered 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

[3] http://webnet.oecd.org/HPV/UI/SIDS_Details.aspx?Key=2c80d506-86bf-4719-be9b-d922022506ec&idx=0

Justification for classification or non-classification

According to the classification criteria of the CLP Regulation (EC) No. 1272/2008 structurally anaolgue substances need to be cassified as Acute Tox. 4, H302. Based on read-across the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2) is, therefore, also classified accordingly.

The available data on acute dermal toxicity obtainded with structurally analogue substances 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 read-across the target substance is also not classified for acute dermal toxicity.