Sulfonic acids, shale-oil, sodium salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

initiated: 2016-08-22, experimental: 2016-11-28 to 2017-01-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

OECD 420 testing has been considered to be best for this type of substance. In addition the study has been commissioned before Regulation (EU) 2016/863 entered into force.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

MHRA, date of issue: 28/10/2016

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sulfonic acids, shale-oil, sodium salts

EC Number:

297-668-0

EC Name:

Sulfonic acids, shale-oil, sodium salts

Cas Number:

93686-18-1

Molecular formula:

Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance)

IUPAC Name:

Sulfonic acids, shale-oil, sodium salts

Test material form:

liquid - solid: mixture of

Remarks:

aqueous solution

Details on test material:

Tiroler Steinöl sulfoniert D90 (TS-D90)

Specific details on test material used for the study:

technical grade: aqueous solution (31% dry matter in water)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

ANIMAL INFORMATION
Female Wistar (RccHan™:WIST) strain rats were supplied Ьу Envigo RMS (UK) Limited, Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization period of at least 5 days the animals were selected at random and given а number unique within the study Ьу indeliЬle ink-marking on the tail and а number written on а cage card. At the start ofthe study the animals were 8 to 12 weeks of age. The body weight variation did not exceed ±20% of the mean body weight at the start of treatment.

ANIMAL CARE AND HUSBANDRY
The animals were housed in groups ofup to four in suspended solid-floor polypropylene cages fumished with woodflakes. With the exception of an ovemight fast immediately before dosing and for approximately 3 to 4 hours after dosing, free access to mains drinking water and food (2014С Teklad Global Rodent diet supplied Ьу Envigo RМS (UK) Limited, Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that would reasonaЬly be expected to affect the purpose or integrity ofthe study. The temperature and relative humidity were set to achieve limits of 19 to 25 ос and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled Ьу а time switch to give 12 hours continuous light and 12 hours darkness. The animals were provided with environmental eшichment items which were considered not to contain any contaminant of а level that might have affected the purpose or integrity of the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE: No vehicle used
DOSE LEVELS: 300 mg/kg and 2000 mg/kg

Doses:

300 mg/kg and 2000 mg/kg bw

No. of animals per sex per dose:

1 female 300 mg/kg
1 female 2000 mg/kg (absence of toxicity at a dose level of 300 mg/kg)
4 female 2000 mg/kg (absence of toxicity at a dose level of 2000 mg/kg)

Control animals:

no

Details on study design:

STUDY DESIGN
1) In the absence of data regarding the toxicity ofthe test item, 300 mg/kg was chosen as the starting dose.
А single animal was treated as follows:
- dose level: 300 mg/kg
- concentration: 30 mg/mL
- dose volume: 10 mL/kg
- rats: 1, female

2) In the absence oftoxicity at а dose level of 300 mg/kg, an additional animal was treated as follows:
- dose level: 2000 mg/kg
- specific gravity: 1.098
- dose volume: 1.83 mL/kg
- rats: 1, female

3) In the absence of toxicity at а dose level of 2000 mg/kg, an additional group of animals was treated as follows:
- dose level: 2000 mg/kg
- specific gravity: 1.098
- dose volume: 1.83 mL/kg
- rats: 4, female

А total of five animals were therefore treated at а dose level of2000 mg/kg in the study. All animals were dosed once only bу gavage, using а metal cannula attached to а graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival ofthe previously dosed animals. Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and puЬlic holidays. Individual body weights were recorded on Day О (the day of dosing) and on Days 7 and 14. At the end ofthe observation period the animals were killed Ьу cervical dislocation. All animals were subjected to gross necropsy. This consisted of an extemal examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

No statistical analysis performed

Results and discussion

Preliminary study:

NDA

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

There were no signs of systemic toxicity.

Body weight:

Аll animals showed expected gains in body weight.

Gross pathology:

All animals were subjected to gross necropsy. No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to bе greater than 2000 mg/kg body weight (Globally Harmonized Classification System- Unclassified).

Executive summary:

Methods

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat. Following а sighting test at dose levels оf 300 mg/kg and 2000 mg/kg, а further group offour fasted females was given а single oral dose of test item at а dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

- There were no deaths.

- There were no signs of systemic toxicity.

- Аll animals showed expected gains in body weight. Necropsy.

- No abnormalities were noted at necropsy.

Conclusion

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to Ье greater than 2000 mg/kg body weight (Globally Harmonized Classification System: unclassified).