Hexane-1,3,6-tricarbonitrile

Endpoint summary

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:

2022.06.9-2022.09.21

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)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Species:

rat

Strain:

Wistar

Remarks:

WISTAR rats Crl: WI(Han) (full barrier)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Charles River, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 175-180g
- Fasting period before study: 16-18 hours
- Housing: Full barrier in an air-conditioned room
- Historical data: none
- Diet (e.g. ad libitum): libitum
- Water (e.g. ad libitum):libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.7 – 21.4 °C
- Humidity (%): 40 – 63%
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Based on OECD Guideline 423, Annex2

MAXIMUM DOSE VOLUME APPLIED: 2000mg/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: the LD50 value in rats was estimated to be 1200 mg/kg bw

Doses:

2000, 300 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: every 7 days
- Necropsy of survivors performed: yes
- Clinical signs including body weight: none

Sex:

not specified

Dose descriptor:

LD50 cut-off

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

Under the conditions of the present study, a single oral application by gavage of the test item Hexane-1,3,6-tricarbonitrile to rats at a dose of 2000 mg/kg bw was associated with signs of toxicity and mortality.
Under the conditions of the present study, a single oral application by gavage of the test item Hexane-1,3,6-tricarbonitrile to rats at a dose of 300 mg/kg bw was associated with signs of toxicity but no mortality.

Body weight:

lower than 10% body weight loss

Remarks:

None of the animals showed weight loss during the observation period except for the animal No. 6 which showed a weight loss of 13% on the day 5 post-dose, but gain the weight of 9 % till end of the study

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of the present study, a single oral application by gavage of the test item Hexane-1,3,6-tricarbonitrile to rats at a dose of 2000 mg/kg bw was associated with signs of toxicity and mortality.
Under the conditions of the present study, a single oral application by gavage of the test item Hexane-1,3,6-tricarbonitrile to rats at a dose of 300 mg/kg bw was associated with signs of toxicity but no mortality.
The median lethal dose of Hexane-1,3,6-tricarbonitrile after a single oral administration to female rats, observed over a period of 14 days is:
LD50 cut-off (rat): 2000 mg/ kg bw
On the basis of the test results and in conformity with the criteria given in GHS (Globally Harmonized System of Classification and Labelling of Chemicals), the substance should be classified into Category 4: > 300 – 2000 mg/kg bw.

Executive summary:

Under the conditions of the present study, a single oral application by gavage of the test item Hexane-1,3,6-tricarbonitrile to rats at a dose of 2000 mg/kg bw was associated with signs of toxicity and mortality.
Under the conditions of the present study, a single oral application by gavage of the test item Hexane-1,3,6-tricarbonitrile to rats at a dose of 300 mg/kg bw was associated with signs of toxicity but no mortality.
The median lethal dose of Hexane-1,3,6-tricarbonitrile after a single oral administration to female rats, observed over a period of 14 days is:
LD50 cut-off (rat): 2000 mg/ kg bw
On the basis of the test results and in conformity with the criteria given in GHS (Globally Harmonized System of Classification and Labelling of Chemicals) [9], the substance should be classified into Category 4: > 300 – 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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:

2022.06.09-2022.08.24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

Wistar

Remarks:

WISTAR rats Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 193-200g
- Fasting period before study: 24hours
- Housing:Full barrier in an air-conditioned room
- Historical data:
- Diet (e.g. ad libitum): libitum
- Water (e.g. ad libitum):libitum
- Acclimation period:at least 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.7 – 20.9 °C
- Humidity (%): 44 – 63%
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: the dorsal area of the trunk
- % coverage: No less than 10% of the body surface
- Type of wrap if used: a semi-occlusive dressing made of a porous gauze and non-irritating tape and was fixed with an additional dressing in a suitable manner.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the residual test item was removed using aqua ad injectionem
- Time after start of exposure: 24hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on day 1, days 8 and
- Necropsy of survivors performed: yes

Preliminary study:

One animal was administered at a dosage of 2000mg/kg bw as the starting dose. As the animal survived, this dose was used as a starting dose for the main study.

Sex:

female

Dose descriptor:

other: Acute Toxicity Estimate(ATE)

Effect level:

> 2 000 - <= 5 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Body weight:

lower than 10% body weight loss

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the conditions of the present study, single dermal application of the test item Hexane-1,3,6-tricarbonitrile to rats at a dose of 2000 mg/kg bw was associated with no mortality and neither signs of toxicity nor signs of irritation.
According to OECD guideline 402 [4] the test item Hexane-1,3,6-tricarbonitrile has no obligatory labelling requirement for percutaneous toxicity and is not classified.
The Acute Toxicity Estimate according to GHS (Globally Harmonized Classification System), 2021 [9] was determined to be 2000 < ATE ≤ 5000 mg Hexane-1,3,6-tricarbonitrile / kg body weight.

Executive summary:

Under the conditions of the present study, single dermal application of the test item Hexane-1,3,6-tricarbonitrile to rats at a dose of 2000 mg/kg bw was associated with no mortality and neither signs of toxicity nor signs of irritation.
According to OECD guideline 402 [4] the test item Hexane-1,3,6-tricarbonitrile has no obligatory labelling requirement for percutaneous toxicity and is not classified.
The Acute Toxicity Estimate according to GHS (Globally Harmonized Classification System), 2021 [9] was determined to be 2000 < ATE ≤ 5000 mg Hexane-1,3,6-tricarbonitrile / kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw