Reaction mass of sodium 1-methoxy-1-oxohexadecane-2-sulphonate and sodium methyl 2-sulphooctadecanoate

Endpoint summary

Description of key information

Studies performed according to OECD test guidelines and GLP principles:

LD50 oral of the reaction mass lies between 300 and 2000 mg/kg bw.

LD50 dermal of the reaction mass >2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08-28 April 2010

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 12 weeks
- Weight at study initiation: 167-203 g
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (containing sterilized sawdust as bedding material and paper as cage-enrichment.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8-21.5
- Humidity (%):34-53
- Air changes (per hr): approx 15x
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 08 April 2010 to 28 April 2010

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/ml or 30 mg/ml
- Justification for choice of vehicle: based on trail formulations

Maximal dose volume: 10 ml/kg

Doses:

2000 mg/kg
300 mg/kg

No. of animals per sex per dose:

3 animals at 2000 mg/kg
6 animals at 300 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:observations daily (first day: 3x), weighing weekly
- Necropsy of survivors performed: yes (all animals)
- Other examinations performed: clinical signs, body weight, macroscopic examination

Statistics:

no

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Remarks:

formulated in water

Mortality:

no mortality at 300 mg/kg
all three animals at 2000 mg/kg were found dead on Day 1

Clinical signs:

other: 2000 mg/kg: lethargy, flat and/or hunched posture, uncoordinated movements, piloerection, laboured respiration, ptosis. 300 mg/kg: hunched posture, piloerection. The animals (at 300 mg/kg) had recovered from the symptoms between Days 2 and 5.

Gross pathology:

Macroscopic post mortem examination of the animals treated at 2000 mg/kg, which were all found dead during the study, revealed dark red discolouration of the glandular mucosa of the stomach and dark red discolouration of the small intestines together with reddish contents.
Macroscopic post mortem examination of the surviving animals, which were treated at 300 mg/kg did not reveal any abnormalities

Other findings:

none

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Category 4 according to Regulation (EC) No 1272/2008

Conclusions:

The oral LD50 value of MIZULAN FL-80 in Wistar rats was established to be within the range of 300-2000 mg/kg body weight. According to the Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures, the test substance should be classified as Category 4 and should be labeled as H302: Harmful if swallowed.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study has been performed according to OECD guidelines. No data was present in the publication on whether the study was performed according to GLP principles. This is a supporting study as the test substance is similar as both components in the reaction mass, though with a shorter carbon chain length.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

300 - 2 000 mg/kg bw

Based on:

test mat.

At the 2000 mg/kg dose, spontaneous locomotor activity decreased immediately, and diarrhea was reported in all rats within 1 hr. The body weight of the 1 surviving male was decreased on the day after treatment and increased the next day.

In the 300 mg/kg groups, loose stool or diarrhea was observed in 2 males and 1 female on the day of treatment and was gone the next day. The mean body weight did not differ significantly from the control group. Macroscopic examination of all surviving rats showed no remarkable changes. The LD50 was reported to be 1000 mg/kg for males and 500 for females.

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Category 4 according to Regulation (EC) No. 1272/2008

Conclusions:

Acute tox Category 4, H302

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

26 May 2000 - 29 May 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study has been performed according to OECD and EC guidelines and according to GLP principles. Although this is an excellent study, the test substance is only the main component of the reaction mass. The study performed on the test substance to be registered is chosen as the key study for this endpoint.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan Inc., Kanagawa, Japan
- Age at study initiation: 5 weeks
- Weight at study initiation: male: 108-123 g; female: 101-112 g
- Fasting period before study: overnight (free intake of water)
- Housing: stainless steel cage with stainless steel grid floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 56-60
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 7.86 w/v% as 786 mg/kg; 9.83 w/v% as 983 mg/kg; ...; 24w/v% as 2400 mg/kg
- Amount of vehicle (if gavage): 1.0 mL/100 g bw
- Justification for choice of vehicle: the substance has low solubility in water at room temperature; it formed a pearl-like solid material when stirred in high concentration and it was impossible to prepare a stable and even mixture solution.

Doses:

786, 983, 1229, 1536, 1920 and 2400 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:at least once a day; weighing at days 0, 1, 3, 7, and 14 after administration.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

The lethal dose was calculated according to the rate of death at the end of observation period for 14 days using Probit method.

Sex:

male

Dose descriptor:

LD50

Effect level:

2 142 mg/kg bw

Based on:

test mat.

95% CL:

1 656 - 6 654

Sex:

female

Dose descriptor:

LD50

Effect level:

1 819 mg/kg bw

Based on:

test mat.

95% CL:

1 347 - 3 170

Mortality:

Mortality occurred at doses of 983 mg/kg bw or more for males and at 1536 mg/kg bw or more for females. Most mortalities were observed 6 to 24 hours after administration.

Clinical signs:

other: Decreased locomotor activity, ptosis, diarrhea, soiling of the perineal region and piloerection were observed in treated groups. Most clinical signs in the survivors showed a tendency for recovery on the day following administration and had disappeared af

Gross pathology:

For the animals that died from 6 to 24 hours after administration, necropsy showed distension of the stomach with a watery content in both male and female. There was no necropsy findings for the animals that died 4 days after administration nor for the survivors.

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Category 4 according to Regulation (EC) No. 1272/2008

Conclusions:

Based on the results of the LD50 for females, the substance is regarded as harmful if swallowed.

Endpoint conclusion

Dose descriptor:

LD50

Value:

300 mg/kg bw

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:

experimental study

Adequacy of study:

key study

Study period:

15-29 April 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation:10 weeks old
- Weight at study initiation: males average 312 g, females average 183 g
- Fasting period before study: no
- Housing: Individually housed in labeled Macrolon cages containing sterilized sawdust as bedding material and paper as cage-enrichment.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):19.8 - 21.5
- Humidity (%): 34-60
- Air changes (per hr): approx 15x
- Photoperiod (hrs dark / hrs light): 12-12

IN-LIFE DATES: From 15 April 2010 to 29 April 2010

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: back of the animal
- % coverage: The test substance formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18cm² for females.
- Type of wrap if used: a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): water
- Time after start of exposure: 24 hours (at removal of the patch)

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 ml/kg
- Concentration (if solution): 200 mg/ml in water
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 females and 5 males

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing weekly observations daily
- Necropsy of survivors performed: yes (all animals)
- Other examinations performed: clinical signs, macroscopic examination

Statistics:

no data

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality occurred

Clinical signs:

other: Chromodacryorhhoea was noted in four males and two females on Day 1. Hunched posture and piloection were noted in one female on Day 2. Scales, scabs, necrosis, general erythema, and/or scars were seen in the treated skin-area of the animals during the obs

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

GHS criteria not met

Remarks:

Not classified according to Regulation (EC) No. 1272/2008

Conclusions:

The dermal LD50 value of MIZULAN FL-80 in Wistar rats was established to exceed 2000mg/kg body weight.
Based on these results, MIZULAN FL-80 does not have to be classified and has no obligatory labeling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007) and the Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Oral:

In an acute oral toxicity study, according to OECD, EC, EPA and JMAFF test guidelines, rats were exposed via gavage to 2000 and 300 mg/kg bw of Mizulan FL-80 (reaction mass of C16MES and C18MES). Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. All animals at 2000 mg/kg bw died. At 300 mg/kg bw no mortality occurred. At 2000 mg/kg bw lethargy, flat and/or hunched posture, uncoordinated movements, piloerection, laboured respiration, ptosis were observed, and at 300 mg/kg bw hunched posture, piloerection were noted. The animals (at 300 mg/kg) had recovered from the symptoms between Day 2 and 5. Macroscopic post mortem examination of the animals treated at 2000 mg/kg, which were all found dead during the study, revealed dark red discolouration of the glandular mucosa of the stomach and dark red discolouration of the small intestines together with reddish contents. The animals at 300 mg/kg bw showed bodyweight gain which was considered normal and no abnormalities at macroscopic examination were found. Therefore, the oral LD50 of Mizulan FL-80 in rats was establised to be between 300 and 2000 mg/kg bw.

Two supporting studies, one performed with C14MES and the other with C16MES, showed comparable results.

Dermal:

In an acute dermal study, performed according to OECD, and EC test guidelines, rats were exposed by a single dermal application to 2000 mg/kg bw of Mizulan FL-80 for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. No mortality occurred. Chromodacryorhhoea was noted in four males and two females on Day 1. Hunched posture and piloection were noted in one female on Day 2. Scales, scabs, necrosis, general erythema, and/or scars were seen in the treated skin-area of the animals during the observation period. Bodyweight gain was considered normal and no abnormalities at macroscopic examination were found. Therefore, the dermal LD50 of Mizulan FL-80 in rats was established to exceed 2000 mg/kg bw.

Inhalation:

The substance as such are coarse flakes, but this is not marketed into the EU. The substance enters the EU as a powder, but coated with zeolite. The powder without the zeolite coating was physically unstable. This latter was therefore seen as a preparation of the substance. No inhalation study was performed on the powder as no stable untreated powdered substance could be obtained. As the substance will have as end use a detergent used by consumers, the dermal route of exposure was regarded as most likely route of exposure.

Justification for classification or non-classification

The test substance should be classified as Category 4 and should be labeled as H302: Harmful if swallowed.