4-[(4-HYDROXYPYRIMIDIN-2-YL)AMINO]BENZONITRILE

Endpoint summary

Description of key information

 Acute toxicity: Oral: In an acute oral toxicity study in the female outbred albino mouse, following the acute toxic class method in accordance with the OECD Guideline 423, the LD50 was established to be greater than 2500 mg/kg.

 

Acute toxicity: Inhalation: In addition to the oral route of exposure, for substances other than gases, the information mentioned under REACH section 8.5.2 to 8.5.3 shall be provided for at least one other exposure route (REACH Regulation, column 2 adaptation of Annex VIII). For this substance, a study was considered however not deemed scientifically justified for the dermal route of exposure due to its low potential for a significant  rate of absorption through the skin. Based on the fact that the inhalation route of exposure is not considered relevant in the risk assessment for human exposure and the addition of a waiver for the acute dermal toxicity testing, an acute inhalation toxicity study will not be performed.

 

Acute toxicity: Dermal: In addition to the oral route of exposure, for substances other than gases, the information mentioned under REACH section 8.5.2 to 8.5.3 shall be provided for at least one other exposure route (REACH Regulation, column 2 adaptation of Annex VIII). For this substance, an acute dermal toxicity study was considered. However, this can be waived based on the fact that the substance does not meet the criteria for classification for acute toxicity or STOT SE by the oral route, and no systemic toxicity is observed in in vivo studies with dermal exposure.

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:

2004-11-10 to 2004-12-09

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

modified on 2001-12-17

Deviations:

yes

Remarks:

: 1) no characterization of the test material; 2) not sufficient data for the animals tested.

GLP compliance:

no

Remarks:

The study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme, but the study report had not been audited by the QA Unit. No formal claim of GLP compliance was made for the study.

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): T2487

Species:

mouse

Strain:

not specified

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 19-23 g
- Fasting period before study: Animals were fasted before treatment, however, fasting period data were not available.
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS: no data


IN-LIFE DATES: no data

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE: no data

MAXIMUM DOSE VOLUME APPLIED: no data


DOSAGE PREPARATION (if unusual): no data


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: advised in OECD-423 guideline

Doses:

300 mg/kg bw (one group); 2000 mg/kg bw (two groups). Dosing was performed sequentially.

No. of animals per sex per dose:

3 females/group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: no data
- Clinical signs: yes
- Body weight: yes
- Organ weights: no
- Histopathology: no

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Mortality:

No mortalities were reported for the tested concentrations.

Clinical signs:

No signs of systemic toxicity were reported for the tested concentrations.

Body weight:

The bodyweight was within the normal range of variability.

Gross pathology:

No abnormalities were detected in macroscopic observations at 300 and 2000 mg/kg bw dose levels.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test substance in the female outbred albino mouse is estimated to be greater than 2500 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 500 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

 Acute toxicity: Oral: An acute oral toxicity study with T002487 according to the acute toxic class method in female outbred albino mouse, (OECD guideline 423) was performed (Sanders, 2004).

A group of three fasted three females was treated with the test material at a dose level of 300 mg/kg bodyweight. Based on the results from this dose level further groups of fasted females were treated at a dose level of 2000 mg/kg body weight. Dosing was performed sequentially. The test material was administered orally as a suspension in arachis oil BP. Clinical signs and body weight development were

monitored during the study. All animals were subjected to gross necropsy.

There were no deaths and no signs of systemic toxicity.

The acute oral median lethal dose (LD50) of the test material in the female outbred albino mouse was estimated as being greater than 2500 mg/kg bodyweight.

 

Acute toxicity: Inhalation: In addition to the oral route of exposure, for substances other than gases, the information mentioned under REACH section 8.5.2 to 8.5.3 shall be provided for at least one other exposure route (REACH Regulation, column 2 adaptation of Annex VIII). For this substance, a study was considered however not deemed scientifically justified for the dermal route of exposure due to its low potential for a significant  rate of absorption through the skin. Based on the fact that the inhalation route of exposure is not considered relevant in the risk assessment for human exposure and the addition of a waiver for the acute dermal toxicity testing, an acute inhalation toxicity study will not be performed.

 

Acute toxicity: Dermal: In addition to the oral route of exposure, for substances other than gases, the information mentioned under REACH section 8.5.2 to 8.5.3 shall be provided for at least one other exposure route (REACH Regulation, column 2 adaptation of Annex VIII). For this substance, an acute dermal toxicity study was considered. However, this can be waived based on the fact that the substance does not meet the criteria for classification for acute toxicity or STOT SE by the oral route, and no systemic toxicity is observed in in vivo studies with dermal exposure.

 

 

Justification for classification or non-classification

Based on the results, T002487 does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the CLP regulation.

No data were available to decide on the classification for the inhalation route.

No data were available to decide on the classification for the dermal route.