Sodium hydroxyquinoline propanesulfonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Aug 2015 - Jan 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Sodium rac-1-hydroxy-3-(quinolin-6-yl)propanesulfonate

Cas Number:

1609934-65-7

Molecular formula:

C12H12NO4SNa

IUPAC Name:

Sodium rac-1-hydroxy-3-(quinolin-6-yl)propanesulfonate

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species Rat, Wistar strain Crl:WI (Han) (outbred, SPF-Quality). Recognized by international guidelines as the recommended test system (e.g. OECD,
EC).
Number of animals 9 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals.
Age and body weight Young adult animals (approx. 8-9 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
Identification Earmark and tail mark
Health inspection At least prior to dosing. It was ensured that the animals were healthy and without any abnormality that might affect the study integrity.

Conditions
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, at least 10 air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.
Accommodation
Group housing of 3 animals per cage in labeled Makrolon cages (MIV 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).
Acclimatization period was at least 5 days before start of treatment under laboratory conditions.
Diet
Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
Water
Free access to tap water.
Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures. There were no findings that could interfere with the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Oral gavage, using plastic feeding tubes. The test item preparations were
stirred on a magnetic stirrer during dosing.

Doses:

2000 mg/kg (10 mL/kg) body weight.
300 mg/kg (10 mL/kg) body weight.
Single dosage on Day 1.

No. of animals per sex per dose:

Initially, INC280-C1 was administered by oral gavage to three female Wistar rats at 2000 mg/kg body
weight. In a stepwise procedure two additional groups of three females were dosed at 300 mg/kg body
weight.

Control animals:

no

Details on study design:

The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. The first
group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals
dosed at one step determined the next step, based on the test procedure defined in the guidelines.
The onset, duration and severity of the signs of toxicity were taken into account for determination of
the time interval between the dose groups.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 300 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg, all animals were found dead or sacrificed in moribund condition on Day 1.
At 300 mg/kg, no mortality occurred.

Clinical signs:

other: other: At 2000 mg/kg, lethargy, flat posture, hunched posture, uncoordinated movements, shallow respiration, piloerection, watery discharge from the eyes, ptosis and/or clonic spasms, were noted for the animals on Day 1. At 300 mg/kg, hunched posture and/

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 value of INC280-C1 in Wistar rats was to be within the range of 300-2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.
Based on these results according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments), INC280-C1 should be classified as: harmful if swallowed (Category 4) for acute toxicity by the oral route.