N-((3R,4R)-1-benzyl-4-alkylpiperidin-3-yl)-2-halogeno-N-alkyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Endpoint summary

Description of key information

An acute oral toxicity study (Simon, 2008) is available which is key study. This study resulted a LD50 value of greater than 2000 mg/kg bw/day.

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 21 November to 14 December 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study run to 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:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: From Charles River Deutschland GmbH Stolzenseeweg 32-36 D-88353 Kisslegg/Germany
- Age at study initiation: 11 weeks
- Weight at study initiation: 180-200 g
- Fasting period before study:
- 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 libitum
- Water (e.g. ad libitum): Community tap water from FÜlinsdorf ad libitum
- Acclimation period:

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

IN-LIFE DATES: From: 21 November To: 14 December 2007

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage):
- Justification for choice of vehicle:
- Lot/batch no. (if required): 1310049
- Purity:

Doses:

Two groups, each of three female Sprague Dawley (SPF) rats, were treated at a dosage of 2000 mg/kg body weight.

No. of animals per sex per dose:

three females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body
weights were recorded on day 1 (prior to administration) and on days 8 and 15

Statistics:

No statistical analysis was used.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical signs were observed in the three females of the first group 1 to 5 hours post treatment or up to test day 10 in two females. However, on test day 2 a moderately ruffled fur was noted in one female which persisted and decreased to slight up to

Other findings:

Three females (Nos. 4-6) were found with a distended stomach at necropsy. Otherwise, no macroscopic findings were recorded at necropsy.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose of the test substance after single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight.

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)

Acute toxicity: via dermal route

Endpoint conclusion

Value:

mg/kg bw

Additional information

An acute oral toxicity study was conducted according to OECD 423 using rats (Simon, 2008). Key study.

The median lethal dose of the test substance after single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight.

Justification for selection of acute toxicity – oral endpoint
This study was conducted according to OECD 423 under 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.