Reaction mass of Benzene sulfonic acid, hexadecyl(sulfophenoxy)-,disodium salt and Benzene sulfonic acid, - oxibis[hexadecyl]-, disodium salt

Endpoint summary

Description of key information

The acute oral LD50 is >5000 mg/kg and the acute dermal LD50 is >2000 mg/kg, the highest doses examined.

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:

1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP, guideline study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Remarks:

Not specified in report.

Qualifier:

according to guideline

Guideline:

other: Method B1 in Commission Directive 84/449/EEC

Deviations:

no

Remarks:

Not specified in report

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

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:

Specification
Male and female Sprague-Dawley strain rats were supplied by Charles River (UK) Ltd., Manston, Kent, U.K. At the start of the main study the males weighed 142 - 155g, and the females 132 - 142g, and were approximately five to eight weeks old. After a minimum acclimatisation period of at least five days the animals were selected at random and given a unique number within the study by indelible ink marking on the tail and a number written on a cage card.

Husbandry
The animals were housed in groups of up to five by sex in solid - floor polypropylene cages with sawdust bedding. With the exception of an
overnight fast immediately before dosing and for approximately two hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.) was allowed throughout the study. The animal room was maintained at a temperature of 16 - 22°C and relative humidity of 30 - 56%. On occasions the temperature was below the lower limit specified in the protocol (19°C). This did not affect the purpose or integrity of the study. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The test material was freshly prepared, as required, as a solution at the appropriate concentration in distilled water. All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing. Dose volume 10 ml/kg

Doses:

5000 mg/kg (limit dose), concentration 500 mg/ml

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each
animal was calculated according to its fasted bodyweight at the time of dosing.

Deaths and overt signs of toxicity were recorded 30 minutes, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
Individual bodyweights were recorded on the day of treatment (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.

Statistics:

None

Preliminary study:

Not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

There were no deaths.

Clinical signs:

other: An isolated incident of hunched posture was confined to one male four hours after dosing. No other signs of systemic toxicity were noted during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Preliminary study- The male treated with 5000 mg/kg and the female treated with 3000 mg/kg were found dead one day after treatment. Isolated incidents of systemic toxicity noted were hunched posture and lethargy. Based on this information, a dose level of 5000 mg/kg body weight was initially selected for the main study.

None

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: EU GHS

Conclusions:

The acute oral median lethal dose (LD50) of the test material, DOWFAX 8390, in the Sprague-Dawley strain rat was found to be greater than 5000
mg/kg bodyweight. No symbol and risk phrase are required.

Executive summary:

The acute oral toxicity of a powdered Dowfax 8390 sample was evaluated in rats. The study conformed to OECD Guideline Number 401 and Method B1 in Commission Directive 84/449/EEC.

Subsequent to a range-finding study, five male and five female Sprague-Dawley rats were given a single gavage dose of the test material as a solution in distilled water at a dose level of 5000 mg/kg body weight. Animals were observed at 0.5, 1, 2 and 4 hours after dosing and then once daily for 14 days. Individual body weights were recorded on the day of treatment and on days 7 and 14. Animals were examined for gross pathological changes at the termination of the study.

Oral treatment with the test material did not result in any deaths. One male rat had a hunched posture at four hours after dosing. No other clinical signs were noted. There were no significant effects on body weights during the study and there were no treatment-related post-mortem observations at the termination of the study.

The acute, oral median lethal dose (LD50) of DOWFAX 8390 Surfactant was greater than 5000 mg/kg body weight in the Sprague-Dawley rat.

This degree of oral toxicity does not require classification or labelling according to the criteria of the Commission of the European Communities (Annex VI of Council Directive 67/548/EEC).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Two GLP/Guideline studies have been conducted.

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:

1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP, guideline study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Remarks:

Not specified in report.

Qualifier:

according to guideline

Guideline:

other: Method 83 in Commission Directive 84/449/EEC

Deviations:

no

Remarks:

Not specified in report.

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

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:

Specification
Five male and five female Sprague-Dawley strain rats were supplied by Charles River (UK) Ltd., Manston, Kent, U.K. At the start of the study the males weighed 211 - 239g, and the females 205 - 222g, and were approximately ten to fourteen weeks old. After a minimum acclimatisation period of at least five days the animals were selected at random and given a unique number within the study by indelible ink marking on the tail and a number written on a cage card.

Husbandry
The animals were housed individually in solid-floor polypropylene cages during the 24-hour exposure period. For the remainder of the
study, the animals were housed in groups of five by sex in polypropylene grid-floor cages suspended over trays lined with absorbent
paper. Free access to mains drinking water and food (Rat and Mouse Expanded Diet. No. 1, Special Diet Services Limited, Witham, Essex,
U.K.) was allowed throughout the study.

The animal room was maintained at a temperature of 19 - 25C and relative humidity of 45 - 54%. The rate of air exchange was approximately
15 changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day before treatment the back and flanks of each animal were clipped free of hair using vetrinary clippers to expose a skin area of
approximately 5 cm x 4 cm. A group of five male and five female rats were treated with the test material at a dose level of 2000 mg/kg.

The appropriate amount of the undiluted test material, as received, was pre-weighed into a glass vial. The test material was then applied
uniformly to an area of shorn skin (approximating to 10% of the total body surface area) which had previously been moistened with distilled water. A
piece o f aluminium foil measuring 7 cm x 4 cm was placed over the treatment area and 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 afterr dosing the dressings were examined to ensure that they were securely in place. After the 24-hour contact period the bandage and foil
were carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual
test material. The aninals were returned to group housing for the rest of the study.

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

On the day before treatment the back and flanks of each animal were clipped free of hair using vetrinary clippers to expose a skin area of
approximately 5 cm x 4 cm. A group of five male and five female rats were treated with the test material at a dose level of 2000 mg/kg.

The appropriate amount of the undiluted test material, as received, was pre-weighed into a glass vial. The test material was then applied
uniformly to an area of shorn skin (approximating to 10% of the total body surface area) which had previously been moistened with distilled water. A
piece o f aluminium foil measuring 7 cm x 4 cm was placed over the treatment area and 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 afterr dosing the dressings were examined to ensure that they were securely in place. After the 24-hour contact period the bandage and foil
were carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual
test material. The aninals were returned to group housing for the rest of the study.

Deaths and overt signs of toxicity were recorded 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded on the day of treatment (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.

Statistics:

None

Preliminary study:

Not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity or skin irritation were noted during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

None

None

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: EU GHS

Conclusions:

The acute dermal median lethal dose (LD50) of the test material, DOWFAX 8390-D, in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight. No risk phrase is required according to EEC labelling regulations.

Executive summary:

The acute dermal toxicity of a powdered Dowfax 8390 sample was evaluated in rats. The study conformed to OECD Guideline Number 402 and Method 83 in Commission Directive 841449lEEC.

Five male and five female Sprague-Dawley rats were treated with a single, occluded, dermal application of the undiluted test material to the intact skin which was moistened with distilled water. The material was applied at a dose level of 2000 mg/kg body weight to an area of shorn skin which approximated 10% of the total body surface area. Twenty-four hours after application, the dressing and residual test material were removed. The rats were observed for signs of toxicity and death at 0.5, 1, 2 and 4 hours after dosing and subsequently at least once a day for 14 days. Body weights were recorded on the day of treatment and on days 7 and 14. The rats were examined for gross pathologic changes at the termination of the study.

Dermal application of the test material did not result in any deaths, signs of systemic toxicity or skin irritation. No significant effects on body weight were noted during the study and there were no treatment-related post mortem observations at the termination of the study.

The acute dermal median lethal dose (LD50) of DOWFAX 8390 was greater than 2000 mg/kg body weight in the Sprague-Dawley rat. This degree of dermal toxicity does not require classification or labelling according to the criteria of the Commission of the European Communities (Annex VI of Council Directive 671548lEEC).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Two GLP/Guideline studies have been conducted.

Additional information

The acute oral LD50 is >5000 mg/kg and the acute dermal LD50 is >2000 mg/kg, the highest doses examined.

Justification for selection of acute toxicity – oral endpoint
Four oral gavage studies have been conducted. In the key study of the powder, male and female rats were tested at a dose level of 5000 mg/kg/day with no mortality observed. In a supporting study of the powder, one of three female rats died following dosing at 1500 and 2000 mg/kg/day but this was not considered to affect the conclusion that the oral LD50 is >5000 mg/kg. In two studies of the aqueous formulation, the oral LD50 was >2000 mg/kg in male rats (highest dose examined) and >5000 mg/kg in male and female rats.

Justification for selection of acute toxicity – dermal endpoint
One key study exists on the powder and a supporting study, based on the liquid formulation, are available. In both cases, the dermal LD50 is greater than 2000 mg/kg, the highest dose examined.

Justification for classification or non-classification

The acute oral and dermal median lethal dose (LD50) of DOWFAX 8390 was greater than 5000 and 2000 mg/kg body weight, respectively, in the Sprague-Dawley rat. This degree of dermal toxicity does not require classification or labelling according to the criteria of the Commission of the European Communities (Annex VI of Council Directive 671548lEEC).