Phenol, 2,4-dinitro-, sulfurized, leuco derivatives

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009-01-20 till 2009-02-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline-conform study under GLP without deviations

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Phenol, 2,4-dinitro-, sulfurized, leuco derivatives

EC Number:

266-273-5

EC Name:

Phenol, 2,4-dinitro-, sulfurized, leuco derivatives

Cas Number:

66241-11-0

Molecular formula:

Molecular formula is not available.

IUPAC Name:

Reaction products of 2,4-dinitrophenol with polysulfide, leuco derivatives, sodium salt

Details on test material:

- Name of test material : Leuco Sulfur Black 1
- Physical state: thixotrophic, black, wet paste
- Composition: Leuco Sulfur Black 1:52.75 % (w/w) (calculated by amount of by-compounds)
2,4-Dinitrochlorobenzene: < 20 ppm
2,4-Dinitrophenole: < 20 ppm
Sulfate: 970 ppm
Chloride: 750 ppm
Sodium: 1.3 % (w/w)
Water: 45.75 % (w/w) by Karl-Fischer titration
- Lot/batch No.: ESA0007595
- Expiration date of the lot/batch: 2011-07-11
- Stability under test conditions: Stable under storage conditions.
- Storage condition of test material: At room temperature (range of 20 ± 5 °C), light protected.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories Ltd., Füllinsdorf / Switzerland
- Age at study initiation: 11 weeks
- Weight at study initiation: 175.0 g - 197.7 g
- Fasting period before study: fasted for approximately 15 to16 hours (access to water was permitted)
- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, ad libidum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum
- Acclimation period: 2009-01-20 to 2009-01-26 (females, 2000 mg/kg), 2009-01-22 to 2009-01-28 (females, 2000 mg/kg)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.439 g substance/mL vehicle
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: found to be a suitable vehicle
- Purity: purified water


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw


DOSAGE PREPARATION (if unusual): prior to dosing


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no justification (no data available)

Doses:

2319 mg active ingredient /kg bw equals 4396 mg test item / kg bw (Lueco Sulfur Black 1: 52.75% w/w)

No. of animals per sex per dose:

3 females at 2319 mg/kg bw
3 females at 2319 mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Viability / Mortality: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 and twice daily during days 2-15.
Body Weights: On test days 1 (prior to administration), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1, depending on the occurrence of clinical signs of toxicity. Once daily during days 2-15.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 319 mg/kg bw

Based on:

act. ingr.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: For the first group of animals treated at 2319 mg/kg, no clinical signs were observed in any of the animals on test 1. On test day 2, all three females were noted with black-stained feces and the cage of the animals was changed to facilitate further asses

Gross pathology:

No macroscopic findings were observed at necropsy.

Other findings:

None

Any other information on results incl. tables

Table 2: Number of animals dead [and with evident toxicity] [and time range within which mortality occurred]

Dose (mg/kg bw)	Mortality (# dead/total)	Time range of deaths (hours)	Number with evident toxicity (#/total)
2319	0/3	n.a.	0/3
2319	0/3	n.a.	0/3

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose LD50 (female rat)of Leuco Sulfur Black 1 after single oral administration to female rats, observed over a period of 14 days is greater than 2000 mg/kg body weight

Executive summary:

The acute toxicity of Leuco Sulfur Black 1 by oral application was investigated according to the OECD Guideline 423 under GLP.

Two groups, each of three female HanRcc:WIST (SPF) rats, were treated by oral gavage administration at a dosage of 2319 mg active ingredient / kg body weight (corresponding to 4396 mg test item / kg body weight). The test item was formulated in purified water according to the content of the active ingredient at a concentration of 0.439 g/mL and administered at a dosing volume of 10 mL/kg.

No deaths occurred during the study. Except for black stained feces from test day 2 up to test day 5 at the latest, no clinical signs were noted in all animals during the observation time. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy. LD50 was greater than 2319 mg/kg bw.