Reaction mass of 3-(2-{3-cyanato-5-[2-(3-cyanatoaryl)heteropolycycle-5-yl]aryl}heteropolycycle-5-yl)aryl cyanate and heteropolycycle -2,5-diyldi-3,1-arylene dicyanate

Endpoint summary

Description of key information

In an acute oral toxicity study in rats according to OECD method no. 423, the LD50 was determined to be > 2000 mg/kg bw for males and females.

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

Study period:

28 September to 14 March 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nousan No 8147, Agricultural Production Bureau, November 24, 2000.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: CD (Crl:CD ‘SD’)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: a reputable supplier
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: 195 to 228 g
- Housing: groups of three rats of the same sex, were housed in solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved wood flake bedding. Cages, food hoppers, water bottles and bedding were changed at appropriate intervals.
- Diet (e.g. ad libitum): free access to a standard rodent diet (Rat and Mouse No. 1 Maintenance Diet), except for overnight prior to and approximately four hours after dosing.
- Water (e.g. ad libitum): Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):19 to 23°C
- Humidity (%):40 to 70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): Artificial lighting was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per 24 hours.

IN-LIFE DATES:
- From: 29 September 2011
- To: 20 December 2011

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10mL/kg bodyweight
- Justification for choice of vehicle: not reported

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The dose levels for the study were chosen in compliance with the study guidelines. As no previous toxicological information was available the initial dose level was 300 mg/kg.

Doses:

300 mg/kg and 2000 mg/kg

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Frequency of observations and weighing: twice daily for any mortalities, the weight of each rat was recorded on days 1 (prior to dosing), 8 and 15.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other:
Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation.

Preliminary study:

No

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the study.

Clinical signs:

Clinical signs of reaction to treatment comprised chin rubbing in three animals and post salivation staining in one animal receiving 2000 mg/kg. There were no other clinical signs of reaction to treatment throughout the study.

Body weight:

Low bodyweight gains were recorded between Days 8 and 15 for one female dosed at 300 mg/kg.
All other animals were considered to have achieved satisfactory bodyweight gains throughout the study

Gross pathology:

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute median lethal oral dose (LD50) to rats of LZ1554 was demonstrated to be greater than 2000 mg/kg bodyweight.

Executive summary:

The acute oral toxicity was determined in a GLP-compliant study in accordance with OECD guideline no. 423 (acute toxic class method) on a sinlge dose of 2000 mg/kg. The acute median lethal oral dose (LD50) to rats of LZ1554 was demonstrated to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Klimisch 1 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

Justification for classification or non-classification

Based on the data available the substance is not classified or labeled according to Directive 67/548/EEC (DSD) or Regulation 1272/2008/EC (CLP).