Reaction mass of (2E)-Tridec-2-enenitrile and (2Z)-Tridec-2-enenitrile and (3E)-Tridec-3-enenitrile and (3Z)-Tridec-3-enenitrile

Endpoint summary

Description of key information

oral: The LD50 value in rats was found to be greater than 4165 mg/kg bw.

inhalation: The LC50 value in rats was found to be higher than the saturated vapour concentration (48.6 mg/m^3) of the test substance at room temperature.

dermal: The acute dermal LD50 value was determined to be greater than 2000 mg/kg bw.

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:

1985-02-08 to 1985-02-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

no

Remarks:

but QA statement available

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: BOR: WISW

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: males: 174.4 - 192.2 g; females: 152 - 180 g
- Fasting period before study: 16 h
- Housing: collection caging in Macrolon type III/max 5 rats
- Diet: Ssniff Spezialfutter GmbH (Soest, Germany), ad libitum
- Water: ad libitum
- Acclimation period: 7 days at least

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 2
- Humidity (%): 50-85
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5 mL/ kg bw

Doses:

only one (limit) concentration of 5 mL (according to appr. 4165 mg/kg bw calculated using a densitiy of 0.833 mg/cm^3)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on day 0 and day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (at 20 min, 1 h, 2 h, 3 h, 6 h, 24/38 h, 7/14 days)

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 4 165 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was recorded.

Clinical signs:

The sample induced in the tested dosage no clinical-toxicological symtoms.

Body weight:

Post -dosing weight gains (2 week values) of all animals did not show essential differences.

Gross pathology:

Nothing abnormal was found in the animals necropsied an day 14.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 value was determined to be > 4165 mg/kg bw.

Executive summary:

The acute oral toxicity of the test substance was investigated in a study according to OECD 401. One group of 5 male and 5 female rats of the WISW-strain was used. Based on a range finding study, one limit dose of 5000 µL/kg bw undiluted test substance (corresponding to 4165 mg/kg bw) was applied by gavage. Any signs of reaction and mortalities were recorded during the 14-day observation period, animals which died and those killed terminally were subjected to necropsy. The test substance did not induce clinical-toxicological symptoms. Post -dosing body weight gains (2 week values) of all animals did not show essential differences. No mortalities were observed. No changes were observed in the animals necropsied on day 14. Based on these findings, the LD50 value for acute oral toxicity in rats was determined to be > 4165 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

4 165 mg/kg bw

Quality of whole database:

OECD study, good study documentation, QA statement in the report, study well performed, according to ECVAM criteria

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-02-13 to 1989-02-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: females: 121-148 g, males: 150-177 g
- Housing: individually in tiered, stainless steel animal cages
- Diet: ad libitum, no food during exposure
- Water: ad libitum, no water during exposure

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.2 °C during exposure
- Humidity (%): 42.2 during exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: modular glass sections: cylindrical central animal exposure section of 11.45 L volume with top and bottom end cones of 3.31 L volume
- Exposure chamber volume: total chamber volume of 18.07 L, about 33 air change equivalents per hour
- Source and rate of air: 10 L/min
- Treatment of exhaust air: exhaust air was passed through an activated charcoal filter

TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Remarks:

the chamber concentration was checked in 15 minute intervals

Duration of exposure:

4 h

Concentrations:

nominal concentration: 7.8 ppm, corresponding to 62.5 mg/m^3 (calculated by the weight of the test substance divided by the volume of air passing through the exposure system)
measured concentration: 6.1 ppm (48.6 mg/m^3)
control group: 0 mg/m^3

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weights were recorded on the day of exposure and on the following days 2, 3, 4, 8 and 15 (postmortem). The animals were observed at least twice during working days and at least once at weekends for adverse toxicological effects.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology (kidneys, liver, lungs and spleen were taken for histological examination), other: food consumption was measured at weekly intervals

- The target vapour concentration was 7 ppm, which was the maximum concentration that could be generated at room temperature, as determined in preliminary experiments without animals.

Statistics:

Body weights and organ weights were analysed for statistically significant differences using the Student's t-test.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 6.1 ppm

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 6.1 ppm corresponds to 48.6 mg/m^3

Mortality:

No mortality was observed.

Clinical signs:

other: No adverse effects were observed.

Body weight:

No statistically significant differences were observed between the test and control group.

Gross pathology:

No changes were detected.

Other findings:

- Organ weights: No statistically significant differences were observed in the organs when related to the body weights.

Interpretation of results:

GHS criteria not met

Conclusions:

The LC50 value of the test substance as a vapour was determined to be > 6.1 ppm (corresponding to 48.6 mg/m^3), which is the saturated vapour concentration.

Executive summary:

The test substance was assessed for its acute toxicity after single inhalation exposure in a 4 -hours experiment according to OECD 403. 10 Wistar rats (5 males and 5 females) were exposed to the test substance as a saturated vapour (48.6 mg/m^3) in an exposure chamber. Additionally a control group of 20 animals were exposed to air only. The exposure period was followed by a 14 -day observation period. The animals were observed and body weights were recorded at regular intervals. After 14 days, all animals were killed and subjected to post-mortem examination. The kidneys, liver, lungs and spleen were taken for histological examination. All rats survived the treatment without exhibiting clinical symptoms. No abnormalities were found at necropsy and no statistically significant differences between exposure and control group were found with regard to body weight gains or organ weights. As a conclusion, saturated vapour (48.6 mg/m^3) of the test substance was not toxic in this experiment. Therefore the LD50 was determined to be > 6.1 ppm (corresponding to 48.6 mg/m^3).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

48.6 mg/m³

Quality of whole database:

well documented study report of OECD-Guideline and GLP-conform study

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:

1985-06-10 to 1985-06-24

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1981

Deviations:

yes

Remarks:

On 5 occasions the relative humidity was beyond the 70 % recommended by the Guideline for 4-22 h. Following cage-side observations revealed no abnormalities.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1983

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adult animals
- Weight at study initiation: males: 282-370 g, females: 210-233 g
- Fasting period before study: none
- Housing: individually in Macrolon cages
- Diet: ad libitum standard laboratory diet (Hope Farms, Woerden, The Netherlands)
- Water: tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 45-90
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lateral area
- % coverage: ca. 10 % of total body surface
- Type of wrap if used: aliminum foil, fixed with flexible bandage

REMOVAL OF TEST SUBSTANCE
- Washing: the skin was gently dabbed with wet tissues in order to remove remaining test substance
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw

Duration of exposure:

24 h

Doses:

one limit dose of 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Statistical analysis was not carried out as no deaths occured.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured at the limit dose of 2000 mg/kg bw.

Clinical signs:

Slight irritation was observed accompanied by spots with severe irritation in 4 animals during the first few days.

Body weight:

Group mean body weights were slightly reduced for the males and unchanged in females on day 7, but returned to normal by the end of the study.

Gross pathology:

No treatment related gross abnormalities were found.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test substance was determined to be greater than 2000 mg/kg bw.

Executive summary:

A limit study on acute dermal toxicity was conducted according to OECD 402 in rats. 5 male and 5 female Wistar rats were dermally treated with one dose of 2000 mg/kg bw of the test substance. The substance was applied under occlusion and the patches remained on the skin sites for 24 hours. The skin was gently dabbed with wet tissues in order to remove remaining test substance after removal. During the 14 -day observation period no deaths occurred and no signs of systemic toxicity were noted. Irritated skin sites found on all animals returned to normal by the end of the observation period. No test item related macroscopic findings were reported at autopsy. Based on these results, the dermal LD50 value was determined to be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

well documented study report of OECD-Guideline and GLP-conform study

Additional information

Acute oral toxicity:

The acute oral toxicity of the test substance was investigated in a study according to OECD 401. One group of 5 male and 5 female rats of the WISW-strain was used. Based on a range finding study, one limit dose of 5000 µL/kg bw undiluted test substance (corresponding to 4165 mg/kg bw) was applied by gavage. Any signs of reaction and mortalities were recorded during the 14-day observation period, animals which died and those killed terminally were subjected to necropsy. The test substance did not induce clinical-toxicological symptoms. Post -dosing body weight gains (2 week values) of all animals did not show essential differences. No mortalities were observed. No changes were observed in the animals necropsied an day 14. Based on these findings, the LD50 value for acute oral toxicity in rats was determined to be > 4165 mg/kg bw.

In an acute oral toxicity study conducted similar to OECD 401 the test substance was administered to mice. Doses of 4.64, 6.81, 8.25 and 10 mL/kg bw (corresponding to 3865, 5673, 6872 and 8330 mg/kg bw calculated using a densitiy of 0.833 g/cm^3) were applied by gavage. Two male mice were tested per dose group. As vehicle, 0.8 % aqueous hydroxypropylmethyl cellulose was used. The animals were observed for a period of 14 days. Mortality was observed on day 1 after treatment. Both animals of the highest dose group and one animal of the 6872 mg/kg bw dose group died. Based on these results, the acute oral LD50 value was determined to be 6872 mg/kg bw in mice.

 

Acute inhalation toxicity:

The test substance was assessed for its acute toxicity after single inhalation exposure in a 4 -hours experiment according to OECD 403. 10 Wistar rats (5 males and 5 females) were exposed to the test substance as a saturated vapour (48.6 mg/m^3) in an exposure chamber. Additionally a control group of 20 animals were exposed to air only. The exposure period was followed by a 14 -day observation period. The animals were observed and body weights were recorded at regular intervals. After 14 days, all animals were killed and subjected to post-mortem examination. The kidneys, liver, lungs and spleen were taken for histological examination. All rats survived the treatment without exhibiting clinical symptoms. No abnormalities were found at necropsy and no statistically significant differences between exposure and control group were found with regard to body weight gains or organ weights. As a conclusion, saturated vapour (48.6 mg/m^3) of the test substance was not toxic in this experiment. Therefore the LD50 was determined to be > 6.1 ppm (corresponding to 48.6 mg/m^3).

 

Acute dermal toxicity:

A limit study on acute dermal toxicity was conducted according to OECD 402 in rats. 5 male and 5 female Wistar rats were dermally treated with one dose of 2000 mg/kg bw of the test substance. The substance was applied under occlusion and the patches remained on the skin sites for 24 hours. The skin was gently dabbed with wet tissues in order to remove remaining test substance after removal. During the 14 -day observation period no deaths occurred and no signs of systemic toxicity were noted. Irritated skin sites found on all animals returned to normal by the end of the observation period. No test item related macroscopic findings were reported at autopsy. Based on these results, the dermal LD50 value was determined to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available data gave no indications for acute toxic properties of the test substance after oral, inhalative or dermal administration. On the basis of these data the substance is not considered to be classified for acute toxicity under Regulation (EC) No 1272/2008 (CLP), as amended for the ninth time in Regulation (EU) No 2016/1179.