reaction product of: C.I. Leuco Sulfur Black 1 with (3-chloro-2-hydroxypropyl)trimethylammonium chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 24. Aug. to 07. Sep. 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

424-510-1

EC Name:

-

Cas Number:

220150-59-4

Molecular formula:

not applicable for UVCB substance

IUPAC Name:

Reaction products of Phenol, 2,4-dinitro-, sulfurized, leuco derivatives and (3-chloro-2-hydroxypropyl)trimethylammonium chloride

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, 4414 Füllinsdorf, CH
- Gender: male and female; females nulliparous and non-pregnant
- Age at study initiation: males: 8 weeks; females: 11 weeks
- Weight at study initiation: males: 197 to 219 g; females: 173 to 189 g
- Fasting period before study: approximately 16 hours
- Housing: standard laboratory conditions. Groups of five in Makrolon type-4 cages with autoclaved standard softwood bedding ("Lignocel", Schill AG, 4132 Muttenz, CH)
- Diet: ad libitum; palleted standard Kliba 343, batch numbers 86/95 and 65/95 rat maintenance diet ("Kliba", Klingentalmühle AG, 4303 Kaiseraugst, CH) (analytical test report demonstrates suitability)
- Water: ad libitum; community tap water from Füllinsdorf (bacteriological assay and chemical water analysis demonstrated suitability)
- Acclimation period: one week after bill of good health

ENVIRONMENTAL CONDITIONS
- Temperature: 21 to 23 °C
- Humidity: 54 to 76 %
- Air changes: 10 to 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

bi-distilled water

Details on oral exposure:

DOSAGE PREPARATION
- The test item was placed into a glass beaker on a tared Mettler PM 480 balance, and the vehicle was added. A weight by volume dilution was prepared using a homogeniser (Ultra-Turrax, Janke & Kunkel, 79219 Staufen, Germany).
- Homogenelty of the test article in the vehicle was maintained during treatment using a magnetic stirrer (Janke & Kunkel. 79219 Staufen, Germany). The preparation was made shortly before dosing.

TREATMENT
- The animals received a single dose of the test article on a mg/kg body weight basis by oral gavage following fasting (access to water was not interrupted). Food was provided again approximately 3 hours after dosing.
- Application volume: 10 mL/kg bw.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Males: 5
Females: 5
Total: 10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations: four times during test day 1, then daily during days 2-15
- Frequency of weighing: test days 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: All animals were examined macroscopically. All animals were killed by intraperitoneal injection of 2.0 mL/kg bw NARCOREN (Rhone Merieux GmbH, 88471 Laupheim, Germany) equivalent to 320 mg/kg bw sodium pentobarbitone and sacrificed by exsanguination.
- Observations recorded: mortality, body weights, macroscopic findings, clinical signs

CLINICAL SIGNS
General behaviour: aggressiveness, vocalisation, restlessness / excitation, nervousness, fear, sedation, somnolence, sleep, coma
Respiration: apnoea, dyspnea, rales
Eye: chromodacryorrhoea, exophthalmos, miosis, mydriasis, whitish discharge, lid adhesion, lacrimation, negative corneal reflex
Nose: rhinorrhoea, epistaxis
Motility: akinesia, ataxia, dropped head, hyperkinesia, hypokinesia, paralysis (flaccid), paralysis (spastic), paddling movements, stiff gait, rolling movements
Body posture: ventral body position, latero-abdominal position, hunched posture
Motor susceptibility: spasms, tonic muscle spasms, clonic muscle spasms, opisthotonus, saltatory spasms, trismus, tremor, muscle-twitching, muscle-twitching (generalised)
Skin: erythema, oedema, necrosis
Various: loss of weight, emaciation, diarrhoea, ruffled fur, salivation, pallor, cyanosis

Statistics:

The LOGIT-Model could not be used as no death occurred.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

0 % of males at 2000 mg/kg bw
0 % of females at 2000 mg/kg bw

Clinical signs:

other: No clinical signs of toxicity were observed during the observation period.

Gross pathology:

Macroscopic findings: No macroscopic findings were noted.

Applicant's summary and conclusion

Interpretation of results:

other: not classifed according to the CLP criteria (EC 1272/2008)

Conclusions:

The LD50 (oral, rat) of test item was found to be greater than 2000 mg/kg bw.

Executive summary:

Acute oral toxicity of the substance was evaluated in an experimental study that was performed according to the OECD Guideline 401 (1987) and EU method B.1 (1992). The test item was administered to 10 rats (5 male, 5 female) by oral gavage, at 2000 mg/kg bw. 0 % death rate was observed. The LOGIT-Model could not be applied to these data. No clinical signs or gross pathology findings were observed. The acute oral toxicity of the test item in rats of both sexes, observed over a period of 15 days, was estimated to be: greater than 2000 mg/kg bw. Therefore, it can be extrapolated that the LD50 is greater than 2000 mg/kg bw.