Fatty acids, C12-18 (even numbered)-methyl esters, sulfonated, sodium salts

Endpoint summary

Description of key information

Acute oral toxicity: The LD50 (rat) is > 2000 mg/kg bw (OECD TG 401, EU Method B.1)

Acute dermal toxicity: The LD50 (rat) is > 2000 mg/kg bw (OECD TG 403, EU Method B.3)

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:

11th January - 21st February, 1994

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

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

Commission Directive 92/69/EEC

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Blackthorn, Bicester, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: No data
- Age at study initiation: 5-8 weeks old
- Weight at study initiation: males 134-148g; females 124-132 g.
- Fasting period before study: Overnight fast immediately before dosing
- Housing: Housed in groups of up to five by sex in solid floor polypropylene cages furnished with woodflakes.
- Diet: ad libitum from 2 hours after dosing. Rat and Mouse Expanded Diet No. 1,
- Water: ad libitum from 2 hours after dosing
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 38-69
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): No data
- Justification for choice of vehicle: No data
- Lot/batch no. (if required): No data
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual):The test material was ground to a fine powder using a mortar and pestle and freshly prepared, as required, as a solution/suspension at the appropriate concentration in DMSO. Homogeneity was assured by the use of a Silverson Homogeniser.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Not applicable

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodywieghts were recorded prior to dosing on Day 0 and on Days 7 and 14 or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology (external examination and opening of the abdominal and thoracic cavities).

Statistics:

Not stated

Preliminary study:

The female was found dead one day after dosing. No clinical signs of toxicity were noted.
Based on this information, a dose level of 2000 mg/kg bw was selected for the main study.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable

Mortality:

Two females were found dead one day after dosing.

Clinical signs:

other: Common signs of systemic toxicity noted were hunched posture, lethargy, decreased respiratory rate and laboured respiration with additional signs of noisy respiration and increased salivation. Surviving animals recovered two to four days after dosing.

Gross pathology:

Abnormalities noted at necropsy of the females that died during the study were haemorrhagic lungs, dark liver, dark kidneys, haemorrhage of the gastric mucosa and hamorrhage fo the small and large intestines. Sloughing of the gastric mucosa was noted at necropsy of one male and one female that were killed at the end of the study. No abnormalities were noted at necropsy of all other animals that were killed at the end of the study.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item was > 2000 mg/kg bw.

Executive summary:

The acute oral toxicity of the test item was assessed in a study performed according to OECD TG 401 and Method B.1 of Commission Dreictive 67/548/EEC using Sprague-Dawley rats. In a preliminary test, 2 rats (one male/one female) were dosed by gavage at 2000 mg/kg bw. The female was found dead one day after dosing. No clinical signs of toxicity were noted. Based on this information, a dose level of 2000 mg/kg bw was selected for the main study. Based on the results of this test, rats (5 males and 5 females) were dosed by gavage at 2000 mg/kg bw/day and observed for 14 days. Two females were found dead one day after dosing. No further deaths were recorded. Common signs of systemic toxicity noted were hunched posture, lethargy, decreased respiratory rate and laboured respiration with additional signs of noisy respiration and increased salivation. Surviving animals recovered two to four days after dosing. Surviving animals showed expected bodyweight gain during the study. Abnormalities noted at necropsy of the females that died during the study were haemorrhagic lungs, dark liver, dark kidneys, haemorrhage of the gastric mucosa and hamorrhage of the small and large intestines. Sloughing of the gastric mucosa was noted at necropsy of one male and one female that were killed at the end of the study. No abnormalities were noted at necropsy of all other animals that were killed at the end of the study. Based on the results of this study, the oral LD50 was determined to be >2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

One key reliable study available.

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:

27 January 1994 to 10 February 1994

Reliability:

1 (reliable without restriction)

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))

Version / remarks:

Commission Directive 92/69/EEC

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

SPECIFICATION
- Five male and five female Sprague-Dawley rats were supplied by Harlan UK Ltd, Blackthorn, Bicester, Oxon, UK.
- At the start of the study animals were 213-234 g (males) or 210-232 g (females) and were 10-14 weeks old.
- After an acclimatisation period of at least 5 days, animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and recording of the number on a cage card.

HUSBANDRY
- Animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes.
- Animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Free access to mains drinking water and food (Rat and Mouse Expanded Diet No 1, Special Diets Services Limited, Witham, Essex, UK) was allowed during the study.
- The animal room was maintained at a temperature of 19 to 22 °C and humidity of 30 to 51 %.
- Rate of air exchange was approximately 15 changes per hour.
- Lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

PROCEDURE
- On the day before treatment, the back and flanks of each animal were clipped free of hair using veterinary clippers to expose a skin area of approximately 5 cm x 4 cm.
- Five male and five female rats were treated with the test item at a dose level of 2000 mg/kg.
- The appropriate amount of the test material (as received) was pre-weighed into a glass vial.
- Test material was applied uniformly to an area of shorn skin (approximating to 10 % of the total body surface area) which had been previously moistened with distilled water.
- A piece of surgical gauze measuring 7 cm x 4 cm was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage (HYPERTIE). The bandage was further secured with a piece of BLENDERM wrapped around each end.
- The animals were caged individually for the 24-hour exposure period.
- Shortly after dosing the dressings were examined to ensure they were securely in place.
- After the 24 hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test item.
- Animals were returned to group housing for the remainder of the test period.
- Test sites were examined for evidence of primary irritation and scored according to the Draize evaluation scheme (attached).
- Animals were observed for deaths or overt signs of toxicity at 0.5, 1, 2 and 4 hours after dosing then once daily for the subsequent 14 days.
- The animals were also observed for any dermal reactions after removal of the dressings and subsequently once daily for the remainder of the study.
- Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Five male and five female

Control animals:

no

Statistics:

EVALUATION OF DATA
- Data evaluations included any relationship between exposure of animals to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
- Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

- No animal deaths took place during the study.
- Mortality data is given in Table 1 (attached).

Clinical signs:

other: - No signs of systemic toxicity were noted during the study. - Individual clinical observations are given in Table 1 (attached).

Gross pathology:

- No abnormalities were noted at necropsy.
- Individual necropsy findings are given in Table 4 (attached).

Other findings:

DERMAL REACTIONS
- Very slight to well-defined erythema was noted at the treatment sites of all animals.
- Very slight oedema was noted at the treatment sites of two males.
- Desquamation and/or slight haemorrhage of dermal capillaries was noted at the treatment sites of three animals.
- Loss of skin elasticity was confined to one male.
- Treatment sites appeared normal three to seven days after dosing.
- Individual dermal reactions are given in Table 2 (attached).

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley rat was determined to be > 2000 mg/kg bw.

Executive summary:

A study was performed in accordance with OECD 402 and EU Method B.3 to assess the acute dermal toxicity of the test material in Sprague-Dawley rats. A group of ten animals (five males and five females) was given a single 24 -hour semi-occluded dermal application of test material to intact skin at a dose level of 2000 mg/kg bw. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination. No animal deaths took place during the study. No signs of systemic toxicity were noted and signs of skin irritation were very slight to well-defined erythema, very slight oedema, slight haemorrhage of dermal capillaries, desquamation and loss of skin elasticity. The treatment sites appeared normal 3 to 7 days after dosing. All animals showed expected gain in bodyweight during the study except for one female which showed bodyweight loss during the first week and expected bodyweight gain during the second week. No abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley rat was determined to be > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

One key reliable study available.

Additional information

Oral toxicity: The acute oral toxicity of the test item was assessed in a study performed according to OECD TG 401 and Method B.1 of Commission Directive 67/548/EEC using Sprague-Dawley rats. In a preliminary test, 2 rats (one male/one female) were dosed by gavage at 2000 mg/kg bw. The female was found dead one day after dosing. No clinical signs of toxicity were noted. Based on the results of this test, rats (5 males and 5 females) were dosed by gavage at 2000 mg/kg bw/day and observed for 14 days. Two females were found dead one day after dosing. No further deaths were recorded. Common signs of systemic toxicity noted were hunched posture, lethargy, decreased respiratory rate and laboured respiration with additional signs of noisy respiration and increased salivation. Surviving animals recovered two to four days after dosing. Surviving animals showed expected bodyweight gain during the study. Abnormalities noted at necropsy of the females that died during the study were haemorrhagic lungs, dark liver, dark kidneys, haemorrhage of the gastric mucosa and hamorrhage of the small and large intestines. Sloughing of the gastric mucosa was noted at necropsy of one male and one female that were killed at the end of the study. No abnormalities were noted at necropsy of all other animals that were killed at the end of the study. Based on the results of this study, the oral LD50 was determined to be > 2000 mg/kg bw.

Dermal toxicity: A study was performed in accordance with OECD TG 402 and EU Method B.3 to assess the acute dermal toxicity of the test material in Sprague-Dawley rats. A group of ten animals (five males and five females) was given a single 24 -hour semi-occluded dermal application of test material to intact skin at a dose level of 2000 mg/kg bw. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination. No animal deaths took place during the study. No signs of systemic toxicity were noted and signs of skin irritation were very slight to well-defined erythema, very slight oedema, slight haemorrhage of dermal capillaries, desquamation and loss of skin elasticity. The treatment sites appeared normal 3 to 7 days after dosing. All animals showed expected gain in bodyweight during the study except for one female which showed bodyweight loss during the first week and expected bodyweight gain during the second week. No abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley rat was determined to be > 2000 mg/kg bw.

Justification for classification or non-classification

Oral toxicity: In a study performed according to OECD TG 401, the LD₅₀ (rat) was reported as > 2000 mg/kg bw. On this basis, classification for acute oral toxicity is not required.

Dermal toxicity: In a study performed according to OECD TG 402, the LD₅₀(rat) was reported as > 2000 mg/kg bw. On this basis, classification for acute dermal toxicity is not required.