Dodecanenitrile

Endpoint summary

Description of key information

Repeated dose toxicity: oral

The predicted No Observed Adverse Effect Level (NOAEL) for Dodecanenitrile (2437-25-4) is considered to be 567.036 mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Repeated dose toxicity: inhalation

Dodecanentirile is a closed-system intermediate; therefore, little to no exposure to workers is expected because the reaction vessels used to manufacture this material are part of multipurpose, closed-system operation. The data provided herein are being submitted in accordance with the U.S. Environmental Protection Agency's interpretation of Section 8(e) of the Toxic Substances Control Act (TSCA).Also, given the use of the chemical as cleanser or washing purpose. Therefore repeated exposure by the inhalation route is unlikely since the use of respiratory mask is common practice in industries. Thus, it is expected that Dodecanentirile shall not exhibit 28 day repeated dose toxicity by the inhalation route. In addition, there is no data available that suggests that Dodecanentirile (2437-25-4) shall exhibit repeated dose toxicity by the inhalation route. Hence this end point was considered for waiver.

Repeated dose toxicity: dermal

The acute toxicity value for Dodecanentirile (as provided in section 7.2.3) is 4230.6mg/kg body weight. Also, given the use of the chemical as a closed-system intermediate; therefore, little to no exposure to workers is expected because the reaction vessels used to manufacture this material are part of multipurpose, closed-system operation. The data provided herein are being submitted in accordance with the U.S. Environmental Protection Agency's interpretation of Section 8(e) of the Toxic Substances Control Act (TSCA). Therefore repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that Dodecanentirile (2437-25-4) shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that Dodecanentirile (2437-25-4) shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary source.

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

To evaluate the toxic potential of Dodecanenitrile in male and female rats by oral gavage for 47 days.

GLP compliance:

not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report):Dodecanenitrile
- Molecular formula :C12H23N
- Molecular weight :181.321 g/mol
- Substance type: Organic

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

not specified

Duration of treatment / exposure:

Forty seven days which included a mating period, gestation and early lactation phase.

Frequency of treatment:

Daily

Remarks:

0, 50, 250 and 1000 mg/kg bw

No. of animals per sex per dose:

Not specified.

Control animals:

yes, concurrent vehicle

Details on study design:

Not specified.

Positive control:

Not specified.

Observations and examinations performed and frequency:

Observations and examinations performed & frequency
CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified

OPHTHALMOSCOPIC EXAMINATION: Not specified

HAEMATOLOGY: Not specified

CLINICAL CHEMISTRY: Not specified

URINALYSIS: Not specified

NEUROBEHAVIOURAL EXAMINATION: Not specified

Sacrifice and pathology:

Sacrifice and pathology
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

Not specified.

Statistics:

Not specified.

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Clinical sign; Statistically significant change as 2 females were not pregnant was observed at the dose level of 1000 mg/kg bw/day.

At the dose level of 250 mg/kg bw/day, no mating was observed for one female.

At the dose level of 50 mg/kg bw/day, one female was not pregnant.

Mortality:

mortality observed, treatment-related

Description (incidence):

Mortality; At the dose level of 1000 mg/kg bw/day one female was killed in extremis on day 3 of the gestation. After giving birth 4 dams died spontaneously on day 1 post partum and two dams were killed in extremis on days 1 and 4 post partum, respectively.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Body weight ; At the dose level of 1000 mg/kg bw/day mean body weight gain for males were reduced in the Pre-pairing period.
Furthermore, a body weight loss was observed during the lactation period in female at 1000 mg/kg bw/day group compare to control.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Food consumption; At the dose level of 1000 mg/kg bw/day mean food consumption for males were reduced in the pre-pairing period. For females, mean food consumption was slightly reduced in the pre-pairing and gestation period and distinctly during the lactation period.

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

Clinical sign; Statistically significant change as 2 females were not pregnant was observed at the dose level of 1000 mg/kg bw/day.

At the dose level of 250 mg/kg bw/day, no mating was observed for one female.

At the dose level of 50 mg/kg bw/day, one female was
not pregnant.

Mortality; At the dose level of 1000 mg/kg bw/day one female was killed in extremis on day 3 of the gestation. After giving birth 4 dams died spontaneously on day 1 post partum and two dams were killed in extremis on days 1 and 4 post partum, respectively.

Body weight ; At the dose level of 1000 mg/kg bw/day mean body weight gain for males were reduced in the
Pre-pairing period.
Furthermore, a body weight loss was observed during the lactation period in female at 1000 mg/kg bw/day group compare to control.

In the dose level of 1000 mg/kg bw/day ,pup body weight seemed to be slightly reduced on day 1 post partum but distinctly reduced on day 4 post partum; however the results were based only on the data of one litter.

At the dose level of 250 and 50mg/kg bw/day, Body weights of male and female pups were slightly reduced on day 1 post partum and similar to the control on day 4 post partum.

Food consumption; At the dose level of 1000 mg/kg bw/day mean food consumption for males were reduced in the pre-pairing period. For females, mean food consumption was slightly reduced in the pre-pairing and gestation period and distinctly during the lactation period.

Organ weight;At the dose level of 250 and 50mg/kg bw/day, Body weights of male and female pups were slightly reduced on day 1 post partum and similar to the control on day 4 post partum.

Gross pathology ;At the dose level of 1000 mg/kg bw/day statistically significant increase in liver weights was observed in male compare to control.
In 1000 mg/kg bw/day group, due to the fact that there was only one female, no conclusion could be reached concerning liver weights.

At the dose level of 250 and 50 mg/kg bw/day, increase in liver weights was observed in female compare to control but not statistically significantly and not dose dependently.

At the dose level of 1000 mg/kg bw/day statistically significant increase in liver size was observed in male compare to control.

For both sexes, unexpected black-brown contents in stomach, intestine and/or caecum were noted in 0, 50, 250 and 1000 mg/kg bw groups, which were considered not to be test item-related.

Dose descriptor:

NOAEL

Effect level:

250 other: mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No statically significant effects were observed in clinical sign, mortality, body weight, food consumption, Organ weight and gross pathology.

Remarks on result:

other: No toxiceffect were observed

Critical effects observed:

not specified

Conclusions:

NOAEL was considered to be 250 mg/kg bw/day for Dodecanentirile (2437-25-4) in male and female rats by oral gavage for 47 days repeated dose study.

Executive summary:

Repeated dose oral toxicity study forDodecanentirile was conducted inmale and female rats for 47 days by oral gavage. The test substance was exposed at the concentration of 0, 50, 250 and 1000 mg/kg bw/day. Statisticallysignificant clinical change, as 2 females were not pregnant was observed at the dose level of 1000 mg/kg bw/day. At the dose level of 1000 mg/kg bw/day one female was killed in extremis on day 3 of the gestation. After giving birth 4 dams died spontaneously on day 1 post partum and two dams were killed in extremis on days 1 and 4 post partum, respectively. At the dose level of 1000 mg/kg bw/day statistically significant increase in liver weights was observed in male compare to control. At the dose level of 1000 mg/kg bw/day statistically significant increase in liver size was observed in male compare to control. No statistically significant and not dose dependent effect were observed in clinical sign, mortality, body weight, food consumption, Organ weight and gross pathology at dose level of 250 and 50 mg/kg bw/day. Therefore NOAEL was considered to be 250mg/kg bw/day forDodecanentirilein male and female rats by oral gavage for 47 days repeated dose study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

567.036 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Data is of K2 reliability and estimated from OECD QSAR database.

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: inhalation, other

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal, other

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose oral toxicity:

The experimental studies and prediction for target and its closest read across substance using log Pow as the primary descriptor were reviewed to determine the toxic nature of Dodecanentirile (2437-25-4) upon repeated exposure by oral route. The studies are as mentioned below as weight of evidence approach:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound Dodecanenitrile . The study assumed the use of male and female Fischer 344 rats in subacute study of 28 days. No significant alterations were noted at the dose level of 567.036 mg/Kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for Dodecanenitrile is considered to be 567.036 mg/Kg bw/day. Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Supporting above data, an experimental study was conducted for target substance by TSCA (US Environmental Protection Agency, 2006) to dermine the toxic nature of Dodecanentirile (2437-25-4). Repeated dose oral toxicity study for Dodecanentirile was conducted in male and female rats for 47 days by oral gavage. The test substance was exposed at the concentration of 0, 50, 250 and 1000 mg/kg bw/day. Statistically significant clinical change, as 2 females were not pregnant was observed at the dose level of 1000 mg/kg bw/day. At the dose level of 1000 mg/kg bw/day one female was killed in extremis on day 3 of the gestation. After giving birth 4 dams died spontaneously on day 1 post partum and two dams were killed in extremis on days 1 and 4 post partum, respectively. At the dose level of 1000 mg/kg bw/day statistically significant increase in liver weights was observed in male compare to control. At the dose level of 1000 mg/kg bw/day statistically significant increase in liver size was observed in male compare to control. No statistically significant and not dose dependent effect were observed in clinical sign, mortality, body weight, food consumption, Organ weight and gross pathology at dose level of 250 and 50 mg/kg bw/day. Therefore NOAEL was considered to be 250mg/kg bw/day for Dodecanentirilein male and female rats by oral gavage for 47 days repeated dose study.

In a study for read across chemical, Repeated dose oral toxicity study was performed by United States Environmental Protection Agency (EPA, HPV Challenge Program, 2017)to determine the mutagenic nature of Distillates, petroleum, hydrotreated light / Kerosine (64742-4-8). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. Repeated dose oral toxicity study for Kerosine was conducted inmale and female Sprague-Dawley rats for 90 days by oral gavage. The test substance was exposed at the concentration of0, 20,100 and 500 mg/kg/day.   Administration of test substance at dose level of 500 mg/kg/day induced slight systemic toxicity in male and female rats, including reduced body wt gain, elevated liver weight, reduced hematology values, and elevated cholesterol which are qualitatively consistent with results of repeat exposure studies of other coal-derived liquids of similar boiling range. As there was no statistically effects were observed in clinical sign, body weight, Food consumption, hematology, gross pathology and histopathology at dose level of 100 and 20mg/kg bw/day .Therefore NOAEL was considered to be 100mg/kg bw/day for Kerosine in male and female Sprague-Dawley rats by oral gavage for 90 days.

The data available for the target chemical Dodecanentirile (2437-25-4) and its read across substance as well as applying weight of evidence approach it can be concluded that the target chemical is not likely to cause repeated dose toxicity. Also the chemical did not induce toxicity to specific target organ. Based on the observations Dodecanentirile does not exhibit toxicity upon repeated exposure and hence the test chemical is not likely to classify as a toxicant upon repeated exposure by oral route.

Repeated dose toxicity: inhalation

Dodecanentirile is a closed-system intermediate; therefore, little to no exposure to workers is expected because the reaction vessels used to manufacture this material are part of multipurpose, closed-system operation. The data provided herein are being submitted in accordance with the U.S. Environmental Protection Agency's interpretation of Section 8(e) of the Toxic Substances Control Act (TSCA).Also, given the use of the chemical as cleanser or washing purpose. Therefore repeated exposure by the inhalation route is unlikely since the use of respiratory mask is common practice in industries. Thus, it is expected that Dodecanentirile shall not exhibit 28 day repeated dose toxicity by the inhalation route. In addition, there is no data available that suggests that Dodecanentirile (2437-25-4) shall exhibit repeated dose toxicity by the inhalation route. Hence this end point was considered for waiver.

Repeated dose toxicity: dermal

The acute toxicity value for Dodecanentirile (as provided in section 7.2.3) is 4230.6mg/kg body weight. Also, given the use of the chemical as a closed-system intermediate; therefore, little to no exposure to workers is expected because the reaction vessels used to manufacture this material are part of multipurpose, closed-system operation. The data provided herein are being submitted in accordance with the U.S. Environmental Protection Agency's interpretation of Section 8(e) of the Toxic Substances Control Act (TSCA). Therefore repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that Dodecanentirile (2437-25-4) shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that Dodecanentirile (2437-25-4) shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Based on the data available for the target chemical and its read across substance, Dodecanentirile (2437-25-4) is considered not to exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure . Hence the substance can not be classified as toxicant.

Justification for classification or non-classification

Based on the data available for the target chemical Dodecanentirile (2437-25-4) and its read across substance as well as applying weight of evidence approach it can be concluded that the target chemical is not likely to cause repeated dose toxicity. Also the chemical did not induce toxicity to specific target organ. Based on the observations Dodecanentirile does not exhibit toxicity upon repeated exposure and hence the test chemical is not likely to classify as a toxicant upon repeated exposure by oral route.