Disodium 2-[4-[[2-cyano-3-[4-[methyl(2-sulphonatoethyl)amino]phenyl]-1-oxoallyl]amino]phenyl]-6-methylbenzothiazole-7-sulphonate

Endpoint summary

Description of key information

The acute oral toxicity in rats of the test item was determined in an OECD guideline study. The LD50 was determined to be > 2000 mg/kg bw

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: animals of comparable weight (± 20% of the mean weight), mean weight: administration 1: 183.3 g, administration 2: 184.0 g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum
- Housing: single housing in Makrolon cages, type III
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany; adlibitum (except during fasting period)
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 – 70
- Air changes (per hr): approx. 10
- Photoperiod (hrs light / hrs dark): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

FORM OF ADMINITRATION: Suspension

VEHICLE
- Concentration in vehicle: 20 g/100 mL
- Justification for choice of vehicle: a good homogeneity in water could not be guaranteed, because the test item preparation was a suspension

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test item was prepared for each test group shortly before administration by stirring with a high speed homogenizer (Ultra-Turrax) and a magnetic stirrer. Additionally, the homogeneity of the test item preparation during administration was ensured by stirring with a magnetic stirrer.

CLASS METHOD
- Rationale for the selection of the starting dose: By request of the sponsor a starting dose of 2000 mg/kg bw was chosen in the first step with 3 female animals. Because no mortality occurred, 2000 mg/kg bw were administered to another group of 3 female animals in the second step.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2 x 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality: A check for any dead or moribund animals was made at least once each workday
Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
Clinical observations: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter
- Necropsy of survivors performed: yes; necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations
- Other examinations performed: clinical signs, body weight

Statistics:

Calculations were performed using Microsoft Excel 2003 and checked with a calculator.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality

Mortality:

No mortality occurred in both test groups.

Clinical signs:

other: In the first administration group impaired general state and piloerection were observed from hour 1 until hour 3 or 4 in all animals. In the second administration group no clinical signs were observed in all animals during clinical examination.

Gross pathology:

There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Conclusions:

Under the conditions of this study the median lethal dose of the test item after oral administration was found to be greater than 2000 mg/kg bw in rats.

Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class method, 2000 mg/kg bw of the test item (preparations in 0.5% CMC-solution) were administered by gavage to two test groups of three fasted female Wistar rats each.

The following test substance-related clinical observations were recorded, clinical signs occurred within the first 4 hours after administration:

2000 mg/kg (first test group):

- No mortality occurred

- Impaired general state in all animals

- Piloerection in all animals

2000 mg/kg (second test group):

- No mortality occurred

- No clinical signs were observed.

The body weights of both test groups increased within the normal range throughout the study period. There were no macroscopic pathological findings in all animals sacrificed at the end of the observation period. The acute oral LD50 was calculated to be greater than 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:

GLP guideline study

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral:

In the key acute oral toxicity study performed according to the Acute Toxic Class method, 2000 mg/kg bw of the test item (preparations in 0.5% CMC-solution) were administered by gavage to two test groups of three fasted female Wistar rats each (BASF SE, 2015). The following test substance-related clinical observations were recorded, clinical signs occurred within the first 4 hours after administration:

2000 mg/kg bw (first test group): No mortality occurred; impaired general state in all animals; piloerection in all animals

2000 mg/kg bw (second test group): No mortality occurred; no clinical signs were observed

The body weights of both test groups increased within the normal range throughout the study period. There were no macroscopic pathological findings in all animals sacrificed at the end of the observation period. The acute oral LD50 was calculated to be greater than 2000 mg/kg bw.

A disregarded study with an aqueous solution of test item (10.8 g/100g active ingredient) was performed ot assess the acute oral toxicity in Wistar rats (OECD guideline 423). A single oral dose of the test material preparation in aqua bidest. was administered by gavage to a group of six fasted animals (three males and three females) at a dose level of 2000 mg/kg body weight. The animals did not show any signs of toxcicity. The expected body weight gain was observed in the course of the study. No mortality occurred. No abnormalities were noted at necropsy of animals sacrificed at the end of the study. Under the conditions of this study the median lethal dose of the test item after oral application was found to be greater than 2000 mg/kg body weight for male and female animals (BASF, 1998). The study was rated as disregarded study as it was only tested in a purity of 10.8 g/100 g active ingredient.

Justification for selection of acute toxicity – oral endpoint
GLP and guideline study

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008 (CLP). As a result the substance is not considered to be classified for acute oral toxicity under Regulation (EC) No 1272/2008.