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Administrative data

Description of key information

Oral LD50 (OECD guideline 423), rat > 2000 mg/kg bw (BASF SE, 2019)
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:
experimental study
Adequacy of study:
key study
Study period:
September 2018 - October 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
For details see analytical report 18L00152
Homogeneity: The test item was homogeneous by visual inspection.
Storage stability: The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
Expiry date: February 2020
Storage conditions: Room temperature
Physical state/ color: Solid / white
Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han) SPF
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable)
- Source: Charles River Wiga GmbH, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: 175-182g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing:
Type of cage: Makrolon cage, type III
Number of animals per cage: Single housing

- Diet (e.g. ad libitum): R/M maintenance, low phytoestrogen; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany), ad libitum
- Water (e.g. ad libitum):Tap water ad libitum
- Acclimation period:Acclimatization period of at least 5 days before the beginning of the experimental phase
- Microbiological status when known: SPF
- Method of randomisation in assigning animals to test and control groups

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +- 3°C
- Humidity (%): 30 – 70%
- Air changes (per hr): Approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
preparations in deionized water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20g/100ml
- Amount of vehicle (if gavage): total admin volume 10ml/kg
- Justification for choice of vehicle:solubility

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg Testitem



CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
Duration of observation period following administration: 14 days
Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter on the last day of observation and on the day of death starting with study day 1.
Clinical observations: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.
Mortality: A check for any dead or moribund animals was made at least once each workday; these records are archived by Bioassay.
Pathology: Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations. Necropsy of all animals that died as early as possible after death.
Histology: No histological examinations were performed.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred in the first 2000 mg/kg test group.
One animal of the second 2000 mg/kg test group was found dead on day 1 after administration.
Clinical signs:
Clinical signs in the first 2000 mg/kg test group revealed in all animals impaired general state and piloerection from hour 1 or 2 until study day 3 after administration, respectively. Cowering position was seen in all animals from hour 2 until hour 4, while reduced defecation was noticed in one of these animals from day 1 until day 2.
Clinical signs in the second 2000 mg/kg test group revealed in all animals impaired general state and piloerection from hour 1 or 2 until hour 5 after administration, respectively. Cowering position and dyspnea were seen in two animals from hour 2 until hour 4, while respiratory noises were noted in one of these animals at hour 1 only.
Body weight:
The body weights of the surviving animals (5 females) increased within the normal range throughout the study period. The animal that died showed weight reduction after death (day 1).
Gross pathology:
The following macroscopic pathologic findings were observed in the single animal that died in the second 2000 mg/kg bw test group:
o Dark discoloration of liver and lung lobes
o Gasified stomach with liquid contents
o Advanced putrefaction. There were no macroscopic pathological findings in any animal sacrificed at the end of the observation period (5 females).
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the median lethal dose of Component in "Confidentail Name" after oral administration was found to be greater than 2000 mg/kg bw in rats.
Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class Method (OECD 423), a dose of 2000 mg/kg bw of the test item Component in "confidential substance name" (preparations in deionized water) were administered by gavage to two test groups of three fasted Wistar rats each (6 females) (BASF SE 2019).
The following test substance-related clinical observations were recorded, clinical signs occurred within the first 3 days after administration:
2000 mg/kg (first test group):
 No mortality occurred
 Impaired general state in all animals
 Piloerection in all animals
 Reduced defecation in one animal
 Cowering position in all animals
2000 mg/kg (second test group):
 Mortality in one animal
 Piloerection in all animals
 Impaired general state in all animals
 Cowering position in two animals
 Dyspnoea in two animals
 Respiratory noises in one animal
 Macroscopic pathological findings in the single animal that died:
o Dark discoloration of liver and lung lobes
o Gasified stomach with liquid contents
o Advanced putrefaction
The body weights of the surviving animals (5 females) increased within the normal range throughout the study period.
There were no macroscopic pathological findings in any animal sacrificed at the end of observation period (5 females).
The acute oral LD50 was calculated to be LD50, oral, rat > 2000 mg/kg bw

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
Study with registred material, KL1

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 an acute oral study regarding C8-18AS Mg&TEA (CAS 85586-38-5) available. Therefore the endpoint acute oral toxicity is covered by this key information. The endpoint acute dermal toxicity is covered by read-across from 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 analog justification 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 analog justification in turn represent the predominant attribute in mediating effects on mammalian health. Therefore, the AS have similar physico-chemical, environmental and toxicological properties, validating the read across approach within the category. The approach of using 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 C8-18AS Mg&TEA (CAS 85586-38-5). Magnesium is a metal occurring ubiquitously in the diet. A tolerable upper intake level (UL) was established by the US Food and Nutrition Board, adapted by the European Food Safety Authority and set to 250 mg/d for adults [4]. This equals 3.6 mg/kg bw/d for an adult of 70 kg bw. Correcting for the molecular weight of the C12AS Mg (approx. 290 g/mol) this corresponds to approx. 43 mg/kg bw/d. This UL is above the derived DNEL for the oral route and based on a slight and reversible laxative effect. Therefore, contribution of magnesium to adverse effects of C8-18AS Mg&TEA (CAS 85586-38-5) on human health is not expected. 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


The Endpoint acute oral toxicity was covered with an acute oral toxicity study performed according to the Acute Toxic Class Method (OECD 423) with the registered substance. Therefore a dose of 2000 mg/kg bw of the test item Component in "confidential substance name" (preparations in deionized water) were administered by gavage to two test groups of three fasted Wistar rats each (6 females) (BASF SE 2019).
The following test substance-related clinical observations were recorded, clinical signs occurred within the first 3 days after administration:
2000 mg/kg (first test group):
 No mortality occurred
 Impaired general state in all animals
 Piloerection in all animals
 Reduced defecation in one animal
 Cowering position in all animals
2000 mg/kg (second test group):
 Mortality in one animal
 Piloerection in all animals
 Impaired general state in all animals
 Cowering position in two animals
 Dyspnoea in two animals
 Respiratory noises in one animal
 Macroscopic pathological findings in the single animal that died:
o Dark discoloration of liver and lung lobes
o Gasified stomach with liquid contents
o Advanced putrefaction
The body weights of the surviving animals (5 females) increased within the normal range throughout the study period.
There were no macroscopic pathological findings in any animal sacrificed at the end of observation period (5 females).
The acute oral LD50 was calculated to be LD50, oral, rat > 2000 mg/kg bw


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. 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 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 using a method 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 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. Thus, 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 study. Findings consist in 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 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, 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 C8-18AS Mg&TEA (CAS 85586-38-5) 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 vapor 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. 


REFERENCES:


[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


[4] EFSA (TOLERABLE UPPER INTAKE LEVELS FOR VITAMINS AND MINERALS, 2006)


http://www.efsa.europa.eu/en/ndatopics/docs/ndatolerableuil.pdf



Justification for selection of acute toxicity – oral endpoint
The study was selected as the LD50 achieved within this study is used for classification purposes.

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 does not meet the criteria for classification as Acute Toxic according to Regulation (EC) 1272/2008 and 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.

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