Alcohols, C11-15-secondary, ethoxylated

Endpoint summary

Description of key information

The oral LD50 for female rats of Softanol 30 was demonstrated to be greater than 2000 mg/kg bodyweight (HLS 2010, PLZ0014).
The dermal LD50 for male and female rats was higher than 2000 mg/kg (RCC 1997, report 650518). A waiver for acute inhalation toxicity has been submitted.  The justification for the waiver is that the study is scientifically not necessary / other information available.  Acute inhalation exposure to Softanol 30 alone as a mist is unlikely because of the processes used to manufacture the substance and the protective measures in place.  Acute inhalation exposure to softanol 30 may occur but will only occur as a mixture with other surfactants which will affect the biological response to the surfactant properties of Softanol 30 which is locally toxic.  Therefore the value of an acute inhalation toxicity study is considered to be too low to justify.  In general the acute inhalation toxicity of secondary alcohol ethoxylates is low (HERA, 2009).    The acute inhalation toxicity of Softanol 30 should not be classified under the CLP regulation.    

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:

18 March 2010 to 09 April 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to internationally accepted guidelines and to GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry ofAgriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nohsan No 8147, Agricultural Production Bureau, November 24, 2000.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd.
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: 225 to 234 g
- Fasting period before study: overnight prior to and approximately four hours after dosing.
- Housing: They were housed in groups of three rats of the same sex, in solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved wood flake bedding.
- Diet (e.g. ad libitum): Rat and Mouse No.1 Maintenance Diet ad libitum except for overnight prior to and approximately four hours after dosing.
- Water (e.g. ad libitum): ad libitum from public supply
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23
- Humidity (%): 40 to 70
- Air changes (per hr): not reported, the animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated.
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 24 March 2010 To: 09 April 2010

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2000mg/mL
- Amount of vehicle (if gavage): 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As some previous toxicological information indicated that the test material should not be toxic the
initial dose level was 2000 mg/kg.

Doses:

2000 mg/kg

No. of animals per sex per dose:

6 females (3 dosed first, results assessed then a further 3 dosed)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Day 1 frequent intervals, on subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only).
The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: all rats humanely killed on day 15 for macroscopic examination
- Other examinations performed: clinical signs, bodyweight, organ weights, histopathology, other: All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the study.

Clinical signs:

other: Clinical signs of reaction to treatment comprised loose faeces, reduced body tone, underactivity, unsteady gait, elevated gait and piloerection seen in all females dosed at 2000 mg/kg. These signs were first noted from approximately thirty minutes after d

Gross pathology:

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information: or unclassified (CLP)

Conclusions:

The acute median lethal oral dose (LD50) to rats of SOFTANOL 30 was demonstrated to be greater than 2000 mg/kg bodyweight. SOFTANOL 30 is included in Category 5 or unclassified, according to the Globally Harmonised System (GHS), (UNITED NATIONS, 2005).

Executive summary:

In an acute oral toxicity study realised according to the OECD guideline 423 and in compliance with GLP, groups of 3 female Sprague Dawley rats were given a single oral dose of  Softanol 30 in corn oil at the dose of 2000mg/kg and observed for 14 days.

There were no deaths during the study. Clinical signs of reaction to treatment were first noted from approximately thirty minutes after dosing and had resolved completely by Day 5. The acute median lethal oral dose (LD50) to female rats of SOFTANOL 30 was demonstrated to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

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:

experimental study

Adequacy of study:

key study

Study period:

24 February 1997 to 10 March 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Conducted to internationally accepted guidelines and to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: HanIbm: WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. Wolferstrasse 4, CH-4414 Fullinsdorf, Switzerland
- Age at study initiation: (age when treated) males 8 weeks, females 11 weeks
- Weight at study initiation: (when treated) Males: 225.2 - 240.3 8, Females: 191.9- 223.8 g
- Fasting period before study: no
- Housing: During acclimatization in groups of five in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz). During treatment and observation individually in Makrolon type-3 cages with standard softwood bedding.
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, batch 81/96 rat maintenance diet (Kliha Muhlen AG, CH-4303 Kaiseraugst) available ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen, available ad libitum.
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 4-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 17 February 1997 To: 10 March 1997

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back (clipped)
- % coverage: 10
- Type of wrap if used: A semi-occlusive dressing wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0 mL
- Concentration (if solution): 100%
- Constant volume or concentration used: yes

Duration of exposure:

24 Hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Four times during test day 1 and once daily for surviving animals during days 2-15. Weighing: On test day 1 (pre-administration), 8 and 15 for surviving animals.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Each animal was examined for changes in appearance and behaviour (with special emphasis on the application area, except for the time when the semi-occlusive dressing was in place) four times during day 1, and once daily for surviving animals during days 2-15. All abnormalities were recorded.

Statistics:

The LOGIT-Model could not be used as no deaths occurred.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical signs of systemic toxicity of the test article on the skin at the application site were observed during the observation period. Local effects such as general erythema and scales on the back were observed in all animals.

Gross pathology:

No macroscopic organ findings were noted at necropsy.

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information: or unclassified (CLP)

Conclusions:

LD50 for male and female rats was >2000 mg/kg.

Executive summary:

In an acute dermal toxicity study realised according to the OECD guideline 402 and in compliance with GLP, groups of 5 male and 5 female rats were dermally exposed to undiluted Softanol 30 for 24 hours to 10% of body surface area (back) at doses of 2000mg/kg bw. Animals then were observed for 14 days. 

No deaths occurred during the study. No clinical signs of systemic toxicity of the test article on the skin at the application site were observed during the observation period. Local effects such as general erythema and scales on the back were observed in all animals. LD50 for male and female rats was >2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity

One study is available and valid.

 

In an acute oral toxicity study realised according to the OECD guideline 423 and in compliance with GLP, groups of 3 female Sprague Dawley rats were given a single oral dose of  Softanol 30 in corn oil at the dose of 2000mg/kg and observed for 14 days (HLS 2010, PLZ0014).

There were no deaths during the study. Clinical signs of reaction to treatment were first noted from approximately thirty minutes after dosing and had resolved completely by Day 5. The acute median lethal oral dose (LD50) to female rats of SOFTANOL 30 was demonstrated to be greater than 2000 mg/kg bodyweight.

 

Acute inhalation toxicity

No data is available for acute inhalation toxicity. A waiver for acute inhalation toxicity is submitted.

All in vivo studies (acute oral toxicity study, acute dermal toxicity study, combined repeat-dose and developmental toxicity study) show that Softanol 30 is a UVCB of low toxicity. The adverse effects associated with Softanol 30 are driven by the primary mechanism of toxicity which is caused by the surfactant properties of the UVCB. Softanol 30 is not a single chemical structure but a series of closely related C11-15 secondary alcohol ethoxylates differing by chain length. The substance is a UVCB with high purity (100%). The 100% purity supports the contention that there should be no unexpected toxicological responses from impurities. The toxicological properties of Softanol 30 are based on the surfactant detergent nature of the constituents. The physicochemical properties are very similar between the different chain lengths because of the closeness of the homologues. The similarity between the properties of the homologues in the mixture allows a consideration of the properties which applies to the entire UVCB.  A review by HERA (2009) of available evidence regarding acute inhalation toxicity reported that alcohol ethoxylates are considered to be of low acute inhalation toxicity to rats with LC₅₀values exceeding the saturated vapour concentration in air. Acute toxic thresholds were reached only when animals were exposed to the undiluted test chemical in the form of a respirable mist or aerosol. The general low toxicity of alcohol ethoxylates regardless of route allows a qualitative estimate of acute inhalation toxicity. However, the quantitative prediction by route-to-route extrapolation from oral to inhalation is not recommended when the mode of inhalation toxicity is likely to be local toxicity, as is the case for Softanol 30.  However, taking into consideration the inhalation exposure route and the fact that significant Softanol 30 exposure will only ever be as part of a mixture (e.g. laundry formulations) whereby the other components of the formulation (including other surfactants) will have a significant impact on the expression of the biological response, the value of conducting an acute inhalation study on softanol 30 alone is considered to be too low.  In addition, taking into account the desire to reduce the number of animals used in the safety assessment of chemicals under REACH and in consideration of only using animal testing as a last resort, it is proposed that the acute inhalation toxicity study of Softanol 30 is to be waived.

 

Acute dermal toxicity

One study is available and valid.

 

In an acute dermal toxicity study realised according to the OECD guideline 402 and in compliance with GLP, groups of 5 male and 5 female rats were dermally exposed to undiluted Softanol 30 for 24 hours to 10% of body surface area (back) at doses of 2000mg/kg bw (RCC 1997, report 650518).  Animals then were observed for 14 days.

No deaths occurred during the study. No clinical signs of systemic toxicity of the test article on the skin at the application site were observed during the observation period. Local effects such as general erythema and scales on the back were observed in all animals. LD50 for male and female rats was >2000 mg/kg.

Reference

HERA (2009) Human and Environmental Risk Assessment on ingredients of European household cleaning products: Alcohol Ethoxylates v2

Justification for classification or non-classification

According to CLP, no classification is required for acute oral toxicity (oral LD50 for rats greater than 2000 mg/kg), acute dermal toxicity (dermal LD50 higher than 2000 mg/kg) or acute inhalation toxicity (study scientifically unjustified but toxicity predicted to be low).