Sulfuric acid, mono-C9-11-alkyl esters, sodium salts

Endpoint summary

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

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to Guideline study. Only basic data given.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Limited information concerning test conditions and/or experimental methods.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

According to guideline.

Route of administration:

oral: gavage

Vehicle:

water

Doses:

no data

No. of animals per sex per dose:

5-10

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 200 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

LD50

Effect level:

977 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

LD50

Effect level:

1 427 mg/kg bw

Based on:

test mat.

Mortality:

Occurred, but no detailed data.

Clinical signs:

Diarrhoea, spastic gait, decreased activity, lateral position, hunched posture, laboured respiration, coma, death.

Body weight:

Not stated.

Gross pathology:

Necropsy of died animals: haemorrhages in gastro-intestinal tract and vascular congestion in the liver
Necropsy of survivors: no adverse effects

Other findings:

Not stated.

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 200 mg/kg bw

Quality of whole database:

The whole data base is reliable 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

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

01 June 2012 - 30 August 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

OECD Guideline study conducted in compliance with GLP regulations According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (Dec 2012)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Details on strain: Wistar / Crl:WI (Han) SPF
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 9 weeks (males) and 13 weeks (females), respectively
- Weight at study initiation: mean (males): 273.0 ± 6.63g; mean (females): 225.8 ± 3.19g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing in Makrolon cage, type III
- Diet (ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water (ad libitum): Tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C
- Humidity: 30 – 70%
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

deionized water

Details on dermal exposure:

TEST SITE
- Area of exposure: clipped epidermis (dorsal and dorsolateral parts of the trunk)
- % coverage: about 40 cm² (corresponds to at least 10% of the body surface)

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing of the application site with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5.71 mL/kg bw
- Concentration (if solution): 35 g/100 mL
- Constant volume or concentration used: yes
- For solids, paste formed: no
- Form of application: solution in deionized water
- Test item preparation and homogenization: For better handling the test item was ground with mortar and pestle. The test item preparation was produced shortly before application by stirring with a magnetic stirrer.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: yes
- Other examinations performed:
Clinical signs: Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.

Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation.
The evaluation of skin reactions was performed according to Draize, J.H. (1959): Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas.

Body weight: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.

Pathology: Necropsy with gross-pathology examination on the last day of the observation period after sacrifice with CO2 in a chamber with increasing concentrations over time.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

No systemic clinical signs were observed during clinical examination.

Body weight:

Males:
The mean body weight of the male animals increased within the normal range throughout the study period.

Females:
The mean body weight of the female animals did not significantly change during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range.

Gross pathology:

There were no macroscopic pathological findings in the animals sacrificed at the end of observation period.

Other findings:

Local effects:
No local effects were observed.

Body weight changes:

Individual body weight changes
Dose [mg/kg bw]	2000
Sex	male
Animal No.	1	2	3	4	5	mean	sd.
Body weight at study day [g]
0	274	267	282	266	276	273.0	6.63
7	278	284	301	281	285	285.8	8.93
14	307	304	330	299	308	309.6	11.93

 

Individual body weight changes
Dose [mg/kg bw]	2000
Sex	female
Animal No.	1	2	3	4	5	mean	sd.
Body weight at study day [g]
0	224	222	230	225	228	225.8	3.19
7	231	220	234	226	230	228.2	5.40
14	237	238	240	239	238	238.4	1.14

sd. = standard deviation

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 reliable and of high quality.

Additional information

There are no data on acute oral and dermal toxicity available for C9-11 AS Na (CAS 84501-49-5). Therefore these endpoints are covered by read across to structurally related alkyl sulfates (AS), i.e. C8 AS Na (CAS 142-31-4) and C12 AS Na (CAS 151-21-3) 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 C8 AS Na (CAS 142-31-4) and two studies for C12 AS Na (CAS 151-21-3) addressing acute oral toxicity available.

The study conducted with C8 AS Na (CAS 142-31-4, analytical purity 100%) was performed according to OECD Guideline 423 with Wistar rats (BASF, 2012). Two groups of three female rats were treated with 2000 mg/kg bw via gavage according to the Acute Toxic Class method. The observation period was 14 days. One animal was found dead 5 h after administration in application group 1. No mortality occurred in the second test group. Clinical signs of toxicity comprised impaired general state, dyspnoea and piloerection. All animals gained weight throughout the whole study period. Upon pathology no findings were observed in the surviving animals of both groups.

The study conducted with C12 AS Na (CAS 151-21-3, analytical purity 100%) 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 details were available. Clinical signs of toxicity comprised of 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.

The second study conducted with C12 AS 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.

Based on the results mentioned above, a LD50 of 1200 mg/kg bw was chosen for C9-11 AS Na (CAS 84501-49-5). 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, analytical purity 2.5%) according to OECD Guideline 402. 5 Wistar rats per sex were treated with 2000 mg/kg bw under semi occlusive conditions for 24 h (BASF, 2012). 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, analytical purity 25.1%) 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 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 C10-16 AS Mg (CAS 68081-97-0, analytical purity 23.5%) 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 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 C12-13 AS K (CAS 91783-22-1, analytical purity 25%) on three male and three female New Zealand White rabbits (Benedict, 1978). Both sexes were dosed at 2000 mg/kg bw 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. 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 C9-11 AS Na (CAS 84501-49-5) 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. 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) 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

Justification for selection of acute toxicity – oral endpoint
The study in which the LD50 was achieved was selected.

Justification for selection of acute toxicity – dermal endpoint
Reliable OECD guideline 402 study.

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.