(E)-3-(benzyl(4-((4-nitrophenyl)diazenyl)phenyl)amino)propanenitrile

Endpoint summary

Description of key information

The substance has low oral or dermal toxicity. The LD50 for orsl or dermal administration is above 2000 mg/kg bw in male and female rats.

 

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:

11 August 1998 to 25 August 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HARLAN WINKLEMANN, Gartenstr. 27, 33178 Borchen, SPF breedng colony
- Age at study initiation: 6 - 10 weeeks
- Weight at study initiation: Males - 190g, Females - 172g
- Fasting period before study: 16 hours before
- Housing: Fully air-conditioned rooms in macrolon cages (type 4) on soft wood granulate in groups of 5
- Diet (e.g. ad libitum): ssniff R/M-H (V 1534), ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 50
- Photoperiod (hrs dark / hrs light): 12 hours dark/ 12 hours light

Route of administration:

oral: gavage

Vehicle:

other: sesame oil (Oleum sesami DAB 10)

Details on oral exposure:

The acute oral toxicity of T-9601 was tested only at a dose level of 2000 mg/kg body weight.
The animals received the compound as a 20 % suspension in sesame oil (Oleum sesami DAB 10), the administration volume being 10 ml/kg body weight.
If no compound-related mortality is produced in this limit test according to the guidelines no full study has to be carried out.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

Males - 5
Females - 5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations twice daily (in the morning and in the afternoon), on weekends and public holidays only once. uring this time animals were weighed weekly.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0 Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: No clinical signs of toxicity related to dose levels where noted during the study.

Gross pathology:

Effects on organs: No macroscopic visible changes were found.

Other findings:

Orange discoloured feces in all animals after 2 days of administration

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results obtained in this study the median lethal dose value (LD50) of the substance for the male & female rat is greater than 2000 mg/kg body weight.

Executive summary:

Study data conducted to EEC-Guideline B.1 of the Directive 92/68/EEC and OECD Guidleines for Testing of Chemicals 401 in compliance with GLP.

The median lethal dose value (LD50) of the substance for the male & female rat is greater than 2000 mg/kg body weight. The substance is not classified as harmful by oral exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 August 1998 to 27 August 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HARLAN WINKLEMANN, Gartenstr. 27, 33178 Borchen, SPF breeding colony
- Age at study initiation: 6 - 10 weeks
- Weight at study initiation: Males - 271g, Females - 215g
- Housing: Fully air-conditioned rooms in macrolon cages (type 3) on soft wood granulate, one animal per cage
- Diet (e.g. ad libitum): ssniff R/M-H (V 1534), ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 50
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

Type of coverage:

occlusive

Vehicle:

other: Sesame Oil (Oleum sesami DAB 10)

Details on dermal exposure:

TEST SITE
- Area of exposure: Approximately 30 cm2
- Type of wrap if used: Foil

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 1.0ml per -0.5g

Duration of exposure:

24 h

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

Males - 5
Females - 5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations twice daily (morning and afternoon), on weekends and bank holidays only once. Animals weighed weekly.
- Necropsy of survivors performed: yes

Statistics:

Not reported.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0 Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: No clinical signs of toxicity related to dose levels was observed during the study.

Gross pathology:

Effects on organs: No macroscopic visable changes were observed.

Other findings:

The skin surface of the animals was large discoloured orange up to day six of the study

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results obtained in the study the median lethal dose value (LD50) of the substance for the male and female rat is greater than 2000 mg/kg body weight.

Executive summary:

Study data conducted to EEC-Guideline B.3 of the Directive 92/68/EEC and OECD Guidleines for Testing of Chemicals 402 in compliance with GLP.

The median lethal dose value (LD50) of the substance for the male & female rat is greater than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

2 000 mg/kg bw

Additional information

Testing on the above endpoints gave the following results:

 Acute toxicity: Oral.

-         LD50: >2000 mg/kg

Acute toxicity: Dermal.

-         LD50: >2000 mg/kg

Acute toxicity: Inhalation.

Not measured.

 

The test substance has a presumed low vapour pressure and is a granular product, hence the potential for the generation of inhalable forms is low. In addition, production and use is done in a closed process without isolation of reaction products. The isolated product are dust free granules (non-dusty solid) which may be formulated into a liquid preparation of low volatility and the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. Dermal exposure is considered to be the appropriate route of exposure and has been assessed accordingly. No acute inhalation test was performed.

The following information is taken into account for any hazard / risk assessment:

Oral, inhalation and dermal acute toxicity are all considered.

 

Justification for classification or non-classification

The above studies have all been ranked reliability 1 according to the Klimish et al system. This ranking was deemed appropriate because the studies were conducted to GLP and in compliance with agreed protocols. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for acute effects is therefore required.