Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 November 2017 to 31 December 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
up-and-down procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Potassium 2,5-dihydroxybenzenesulphonate
EC Number:
244-584-7
EC Name:
Potassium 2,5-dihydroxybenzenesulphonate
Cas Number:
21799-87-1
Molecular formula:
(HO)2C6H3SO3K
IUPAC Name:
potassium 2,5-dihydroxybenzenesulphonate
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source: The Dow Chemical Company, Midland, Michigan (United States)
- Lot No.of test material: YY00G7P285
- Expiration date of the lot/batch: 17 December 2017
- Purity test date: Not specified

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient temperature
- Stability under test conditions: Not determined, assumed stable for the duration of the study
- Solubility and stability of the test substance in the solvent: soluble on Reverse Osmosis water at 200 mg/L. Stability, uniformity of mixture and verification of concentration of the test item in its carrier, was not determined.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: None

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Adminstered undiluted, as received. Test item pre-mixed with Reverse Osmosis water to a concentrstion of 200 mg/mL.

Test animals

Species:
rat
Strain:
Wistar
Remarks:
(RCCHan:WIST)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: Minimum: 189.4 - 213.7g
- Fasting period before study: yes, fasted overnight prior to dosing and until three hours post-dosing.

- Housing: Rats were housed individually in standard polypropylene solid bottom cages which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). These cages have stainless steel top grills with steam sterilized corn cob bedding material. Rack units were rotated once a week.
- Diet (e.g. ad libitum): Teklad certified global high fiber rat pellet feed manufactured by Envigo, USA
- Water (e.g. ad libitum): UV sterilized water filtered through Reverse Osmosis water filtration system
- Acclimation period: 6 to 16 days prior to commencement of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23 °C
- Humidity (%): 49 to 66% relative humidity
- Air changes (per hr): 17 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light and 12 hours darkness, light hours being 06:00 h – 18:00 h which was maintained through an automatic timer.

IN-LIFE DATES: From: To: 1 December 2017 to 31 December 2017

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Reverse Osmosis
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): Dose volume (10 mL/kg body weight).
- Justification for choice of vehicle: Based on solubility to 200 mg/mL in RO water to acheive a limit concentration of 2000 mg K-Salt/kg body weight when dosed at 10 ml/kg bw
- Lot/batch no. (if required): Not specifed

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:
The study was performed as a limit test at a dose level of 2000 mg K-Salt/kg body weight.
No. of animals per sex per dose:
Total Number of Animals Used: Five females (nulliparous and non-pregnant)
The first rat was given a single dose of 2000 mg K-Salt/kg bw. No mortality was observed at this dose level up to 48 hours post dose. Therefore, rat No's 2, 3, 4 and 5 were treated with the same dose level of 2000 mg K-Salt/kg bw, one at a time, separated by minimum of 48 hours post dosing intervals. All rats survived at the dose level of 2000 mg K-Salt/kg bw. As the end point was achieved, no further testing was required.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days following oral dosing
- Frequency of observations and weighing: Rats were observed for signs of toxicity and mortality at 0.5, 1, 2, 3, 4 and 6 hours post-administration on the day of dosing. Subsequently, rats were observed twice a day for morbidity and mortality for a period of 14 days following oral dosing.
- Necropsy of survivors performed: yes, at study termination all rats were humanely euthanised by carbon dioxide asphyxiation and subject to a gross pathological examination consisting of an external examination and opening of abdominal and thoracic cavities. The stomach of each rat was opened, the contents rinsed/removed, and the mucosal surface was examined for signs of irritation, erosions, ulcers or any other findings.
- Other examinations performed: Clinical signs were recorded once a day. Individual body weight was recorded prior to dosing on day 1, and on days 8 and 15.
Statistics:
The LD50 was calculated using the Dixon’s maximum likelihood method using software (AOT 425 StatPgm) and was estimated to be greater than 2000 mg K-Salt/kg body weight in female Wistar rats.
ref: AOT 425 StatPgm (OECD), Acute Oral Toxicity (Guideline 425) Statistical Program, Version 1.0, May 2001.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed in any rat after a single dose of 2000 mg K-Salt/kg body weight and observed for 14 days
Clinical signs:
No signs of toxicity were observed in rats treated with K-Salt at 2000 mg/kg body weight and observed for 14 days
Body weight:
There was a normal increase in the body weight of all the rats during the experimental period.
Gross pathology:
External and visceral examination of terminally sacrificed rats did not reveal any lesions of pathological significance. In absence of any pathological lesion in terminally sacrificed rats, it is concluded that the test item did not produce any treatment related effect at the dose level used in the present study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral estimated LD50 of the K-Salt was estimated to be greater than 2000 mg/kg body weight in female Wistar rats.