2-Pyridinamine, 5-bromo-3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-

Endpoint summary

Description of key information

Acute oral toxicity: A primary oral toxicity study (Beerens-Heijnen, 2010) was available which is key study. This study showed that the oral LD50 value of test substance is established to exceed 2000 mg/kg body weight.

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:

From 03 to 29 September 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study run to a method comparable with current guidelines and to GLP

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Wistar strain Crl:WI (Han) (outbred, SPF-Quality)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Approx. 8 weeks old
- Weight at study initiation: Bodyweight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material and paper as cage-enrichment.
- Diet (e.g. ad libitum): Free access to pelleted rodent diet.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0ºC (actual range: 19.6 – 21.6ºC)
- Humidity (%): A relative humidity of 40-70% (actual range: 42 - 75%)
- Air changes (per hr): Approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

IN-LIFE DATES: From: 03 September 2010 To: 29 September 2010

Route of administration:

oral: gavage

Vehicle:

other: 1% Aqueous carboxymethyl cellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle:
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.
- Lot/batch no. (if required):
- Purity: 1% w/v

Doses:

2000 mg/kg (10 mL/kg) body weight

No. of animals per sex per dose:

3 females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability Twice daily. Body weights Days 1 (pre-administration), 8 and 15. Clinical signs At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes. At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

Statistics:

None stated

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture and/or piloerection were noted in all animals on Day 1.

Gross pathology:

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

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 value of this substance in Wistar rats was established to exceed 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:

1 (reliable without restriction)

Additional information

Acute oral toxicity:

A primary oral toxicity study was conducted according to OECD 423 using rat (Beerens-Heijnen, 2010). Key study.

This study showed that the oral LD50 value of test substance is established to exceed 2000 mg/kg body weight.

Justification for selection of acute toxicity – oral endpoint
Study run to a method comparable with current guidelines and to GLP

Justification for classification or non-classification

Oral LD50 = >2,000 mg/kg (actual value >2,000 mg/kg)

Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.1.1 the substance is not classified for the acute toxicity endpoint.