9-Octadecenoic acid (Z)-, sulfonated, potassium salts

Endpoint summary

Description of key information

The available data suggests that 9-Octadecenoic acid (Z)-, sulfonated, potassium salts has a low potential for acute oral (LD50 >2,723 mg/kg bw) and dermal toxicity (LD50 >2,000 mg/kg bw).

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:

From December 03, 1985 to December 17, 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley derived strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charres River U.K. Limited, Margate, Kent, England
- Age at study initiation: Four to six weeks
- Weight at study initiation: 105 to 140 g
- Fasting period: Access to food only was prevented overnight prior to and approximately 4 h after dosing
- Housing: Metal cages with wire mesh floors
- Diet: Standard laboratory rodent diet (i.e., Labsure LAD 1) ad libitum
- Water: ad libitum
- Acclimation period: minimum period of 6 d
- Identification: Each animal was identified by cage number and ear punching

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C and 22°C minimum and maximum temperatures respectively
- Humidity (%): 63%
- Air changes (per hr): 15 air changes/h
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle

IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 4.4 mL/kg
5.0 g/kg bw based on a specific gravity of 1.125

Doses:

5.0 g/kg bw, equivalent to 2,723 mg/kg bw active ingredient

No. of animals per sex per dose:

Five/sex/dose (main study)
Two/sex/dose (preliminary study)

Control animals:

not specified

Details on study design:

Preliminary study
A trial test was carried out by dosing two male and two female rats at 2,723 mg/kg bw active ingredient.

Main study
A group of ten rats (i.e., five males and five females) was treated at 5.0 g/kg bw

Treatment procedure
The appropriate dose volume of the test substance was administered to each rat using a syringe and plastic catheter.

Observation period
5 and 14 d for preliminary and main studies respectively

Observation
Animals were observed soon after dosing; then at frequent intervals for the remainder of Day 1. On subsequent days the animals were observed at least twice per day. Clinical signs were recorded at each observation.

The following were recorded on the main study:

-The nature, severity, approximate time of onset and duration of each toxic sign.
-Individual bodyweights of rats on Days 1 (day of dosing), 8 and 15.

-All animals on the main study were killed on Day 15 by cervical dislocation and were subjected to a macroscopic post mortem examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of abnormal organs when present was recorded

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 723 mg/kg bw

Based on:

act. ingr.

Mortality:

No deaths occurred during the whole study

Clinical signs:

other: Signs of reaction to treatment observed shortly after dosing in all rats were pilo-erection, abnormal body carriage (i.e., hunched posture), abnormal gait (i.e., waddling) and diarrhea. Recovery as judged by external appearance and behaviour was apparent

Gross pathology:

Terminal autopsy findings were normal.

Interpretation of results:

not classified

Conclusions:

Under the study conditions, the oral LD50 was found to be >2,723 mg/kg bw active ingredient in rats.

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance in CD rats of the Sprague-Dawley derived strain according to OECD Guideline 401. Group of five female and three male fasted rats received a single oral (gavage) dose of 2,723 mg/kg bw active ingredient. Undiluted test substance was administered at a volume of 4.4 mL/kg bw. No mortality occurred and no significant macroscopic abnormalities were seen at necropsy. However, clinical signs were observed (pilo-erection, hunched posture, waddling and diarrhea) in all rats for up to 3 days after treatment. Under the study conditions, the oral LD50 was found to be >2,723 mg/kg bw active ingredient in rats (Kynoch, 1986).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 723 mg/kg bw

Quality of whole database:

KL1, the study was conducted according to OECD Guideline 401.

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:

From June 26, 2014 to August 14, 2014

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Wistar strain, Crl:WI (Han) (outbred, SPF-Quality)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age: Young adult animals (approximately 10-12 weeks old) were selected. Females were nulliparous and non-pregnant
- Body weight: Body weight variation did not exceed +/- 20% of the sex mean
- Housing: Individually housed in labeled Makrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet: Free access to pelleted rodent diet (i.e., SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 d. During the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18 cm).
- Animal identification: Tail mark with indelible ink
- Health inspection: At least prior to dosing. It was ensured that the animals were healthy and that the skin to be treated was intact and free from any abnormality.

ENVIRONMENTAL CONDITIONS
- Temperature: 18 to 24°C
- Humidity: 40 to 70%
- Air changes: 10 air changes/h
- Photoperiod: 12 h light/12 h dark cycle

IN-LIFE DATES: From June 26, 2014 to August 14, 2014

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

Treatment
- Method: Dermal application. Test substance (formulations) were stirred on a magnetic stirrer during application.

- Clipping: 1 d before exposure (i.e., Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

- Application: The test substance formulation was applied in an area of approximately 10% of the total body surface, i.e. approximately 25 cm² for males and 18 cm² for females. The test substance formulation was held in contact with the skin with a dressing, consisting of 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.
*. Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).

- Frequency: Single dosage, on Day 1.

- Dose level (volume): 200 mg/kg (10 mL/kg) bw
1,000 mg/kg (10 mL/kg) bw
2,000 mg/kg (10 mL/kg) bw

- Application period: 24 h, after which dressings were removed and the skin cleaned of residual test substance using tap water.

- Test substance preparation
Vehicle: Water (Elix, Millipore S.A.S., Molsheim, France)
Rationale: The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.
Preparation: The formulations (w/w) were prepared within 4 h prior to dosing. Homogeneity was accomplished to a visually acceptable level. No correction was made for purity of the test substance.

Duration of exposure:

24 h

Doses:

200, 1,000 mg/kg and 2,000 mg/kg bw

No. of animals per sex per dose:

200 and 1,000 mg/kg bw: Three females/dose
2,000 mg/kg bw: Five/sex

Details on study design:

- Study design
Based on the test substance data available, it was considered that severe skin effects may occur after dermal application of the test substance. Therefore, the study was conducted in a step wise fashion in order to select the highest dose that could be tested without causing severe skin effects.
Initially, three females were dosed at 200 mg/kg bw. The absence or presence of systemic and local effects determined the next step. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups. The highest dose causing no severe effects was tested in 5 males and 5 females in total.

- Duration of observation period following administration: 14 d
- Frequency of observations:
- Mortality/Viability: Twice daily.

- Body weights: Days 1 (pre-administration), 8 and 15.

- Clinical signs: At periodic intervals on the day of dosing (i.e., Day 1) and once daily thereafter, until Day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).

- Necropsy: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

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: At 200 mg/kg, chromodacryorrhoea was noted for one animal on Day 1. At 1,000 mg/kg, general erythema was seen in the treated skin area of two animals on Days 2 and 3 and scales (on the flank of the animal) were noted for one animal on Days 7 and 8. At

Gross pathology:

At 200 mg/kg, no abnormalities were found at macroscopic post mortem examination of the animals.
At 1,000 mg/kg, pelvic dilation and isolated gray-white focus/foci were found in the kidneys of one animal, at macroscopic post mortem examination.
At 2,000 mg/kg, no abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

not classified

Conclusions:

Under the study conditions, the dermal LD50 of the test substance was found to be >2,000 mg/kg bw in rats.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance in Wistar strain, Crl:WI (Han) rats according to OECD Guideline 402, in compliance with GLP. Based on available data, it was considered that severe skin effects may occur after dermal application of the test substance. Therefore, the study was conducted in a step wise fashion in order to select the highest dose that could be tested without causing severe skin effects. Initially, groups of three female rats received a single dermal dose of 200 or 1,000 mg/kg bw. Since no severe local or systemic effects were found at these treatment levels, a limit dose of 2,000 mg/kg bw was applied to skin of groups of five female and five male rats as a single dermal application for 24 hours. No mortality occurred and no effect on body weight gain was observed. No significant macroscopic abnormalities were seen at necropsy. However, chromodacryorrhoea was observed on Day 1 in one female and male and some local effects (general erythema and scales in the treated skin-area and/or on the flanks of the animals) were observed during the observation period (Van Huygevoort, 2014).

Under the study conditions, the dermal LD50 of the test substance was found to be >2,000 mg/kg bw in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

KL1, the study was conducted according to OECD Guideline 402.

Additional information

Acute toxicity (oral)

A study was conducted to determine the acute oral toxicity of the test substance in CD rats of the Sprague-Dawley derived strain according to OECD Guideline 401. Group of five female and three male fasted rats received a single oral (gavage) dose of 2,723 mg/kg bw active ingredient. Undiluted test substance was administered at a volume of 4.4 mL/kg bw. No mortality occurred and no significant macroscopic abnormalities were seen at necropsy. However, clinical signs were observed (pilo-erection, hunched posture, waddling and diarrhea) in all rats for up to 3 days after treatment. Under the study conditions, the oral LD50 was found to be >2,723 mg/kg bw active ingredient in rats (Kynoch, 1986).

Acute toxicity (dermal)

A study was conducted to determine the acute dermal toxicity of the test substance in Wistar strain, Crl:WI (Han) rats according to OECD Guideline 402, in compliance with GLP. Based on available data, it was considered that severe skin effects may occur after dermal application of the test substance. Therefore, the study was conducted in a step wise fashion in order to select the highest dose that could be tested without causing severe skin effects. Initially, groups of three female rats received a single dermal dose of 200 or 1,000 mg/kg bw. Since no severe local or systemic effects were found at these treatment levels, a limit dose of 2,000 mg/kg bw was applied to skin of groups of five female and five male rats as a single dermal application for 24 hours. No mortality occurred and no effect on body weight gain was observed. No significant macroscopic abnormalities were seen at necropsy. However, chromodacryorrhoea was observed on Day 1 in one female and male and some local effects (general erythema and scales in the treated skin-area and/or on the flanks of the animals) were observed during the observation period (Van Huygevoort, 2014).

Justification for classification or non-classification

The available data on 9-Octadecenoic acid (Z)-, sulfonated, potassium salts indicates a low potential for acute toxicity (oral and dermal LD50 of >2,723 and >2,000 mg/kg bw, respectively). The substance does not meet the requirement for classification according to CLP (EC 1272/2008) criteria.