Dodecanenitrile

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Toxicity to reproduction:

Since no significant changes were noted relating to effects on reproductive toxicity, the No Observed Adverse Effect Level (NOAEL) was estimated to be 852.5 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with Dodecanenitrile.  

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

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 (if other than submission substance):C12H23N
- Molecular weight (if other than submission substance):181.321 g/mole
- Substance type:Organic

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Remarks on MMAD:

not specified

Vehicle:

corn oil

Details on exposure:

not specified

Details on mating procedure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Appro 128 days

Frequency of treatment:

Daily

Details on study schedule:

not specified

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Positive control:

not specified

Parental animals: Observations and examinations:

not specified

Oestrous cyclicity (parental animals):

not specified

Sperm parameters (parental animals):

not specified

Litter observations:

not specified

Postmortem examinations (parental animals):

not specified

Postmortem examinations (offspring):

not specified

Statistics:

not specified

Reproductive indices:

not specified

Offspring viability indices:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

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

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

852.5 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

reproductive performance

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

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

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

Other effects:

not specified

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Dose descriptor:

other: not specified

Generation:

other: not specified

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Dose descriptor:

other: not specified

Generation:

other: not specified

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Reproductive effects observed:

not specified

Treatment related:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 8 nearest neighbours
Domain  logical expression:Result: In Domain

(((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and "m" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Nitrile by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Nitrile by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acetylenic Carbon [#C] OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Cyano, aliphatic attach [-C#N] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Nitrile by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Metalloids by Groups of elements

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N by Chemical elements

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "k"

Similarity boundary:Target: CCCCCCCCCCCC#N
Threshold=80%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= 4.27

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.73

Conclusions:

Since no significant changes were noted relating to effects on reproductive toxicity, the No Observed Adverse Effect Level (NOAEL) was estimated to be 852.5 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with Dodecanenitrile.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the Reproductive toxicity was estimated for Dodecanenitrile. The study assumed the use of rats in a subacute study. Since no significant changes were noted relating to effects on reproductive toxicity, the No Observed Adverse Effect Level (NOAEL) was estimated to be 852.5 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with Dodecanenitrile.  

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

852.5 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

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

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Reproductive toxicity:

The experimental study 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) to reproduction. The studies are as mentioned below as weight of evidence approach:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the Reproductive toxicity was estimated for Dodecanenitrile.The study assumed the use of rats in a subacute study. Since no significant changes were noted relating to effects on reproductive toxicity, the No Observed Adverse Effect Level (NOAEL) was estimated to be 852.5 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with Dodecanenitrile.  

  

In another experimental study given by TSCA (US Environmental Protection Agency, TSCA,  June 12, 2006), male and female rats were treated with Dodecanenitrile in the concentration of 0, 50, 250 and 1000 mg/kg bw orally by gavage for 47 days (mating period, gestation and early lactation phase). At 1000 mg/kg bw, After giving birth 4 dams died spontaneously on day 1 post partum. Mean body weight gain and food consumption were decreased in male rat and during the lactation period in female rat at 1000 mg/kg bw. One female was not pregnant at 50 mg/kg bw, no mating was observed for one female at 100 mg/kg bw and two females were not pregnant and one female was killed in extremis on day 3 of the gestation at 1000 mg/kg bw. 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. Statistically significant decrease in birth and viability index was observed in 1000 mg/kg bw treated rats as compared to control. Similarly, statistically significant increase in liver weights was observed in male rats. For female, due to the fact that there was only one female, no conclusion could be reached concerning liver weights at 1000 mg/kg bw. Increase in liver weights were observed in 50 and 250 mg/kg bw treated female rats, but not statistically significantly and not dose dependently. Unexpected black-brown contents in stomach, intestine and/or caecum were observed in all groups, which were considered not to be test item-related. In addition, statistically significant decrease in viability index were observed in treated rats at 1000 mg/kg bw as compared to control. At 1000 mg/kg bw, pup body weight were 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 50 and 250 mg/kg bw, Body weights of male and female pups were slightly decrease on day 1 post partum and similar to the control on day 4 post partum. Since there were more pups per litter in these groups this is considered to be incidental. Therefore, No adverse effect level(NOAEL) was considered to be 250 mg/kg for P and F1 generation when male and female rats were treated with Dodecanenitrile orally by gavage for 47 days.

Further supported by experimental study given by United States Environmental Protection Agency (EPA, HPV Challenge Program, 2017) on read across substance Distillates, petroleum, hydrotreated light (CAS no 2437-25-4), Sprague-Dawley female rats were treated with Distillates, petroleum, hydrotreated light in the concentration of 0, 20, 100, 500 mg/kg/day by gavage for approx. 142 days (90 days exposure, 10 days mating, 40-42 days gestation and lactation). No adverse effects on survival, body weight and food consumption throughout the administration period were observed in treated rats as compared to control. Similarly, No effect on reproductive parameters such as length of gestation, Pregnancy indices or in maternal weight gain during gestation as compared to control. No treatment related effects were observed in mean litter size, live births or pup survival and body weight at LD 4, 14 and 21 as compared to control. In addition, no histopathological in treated pups as compared to control. A low incidence of malformations occurred in all groups, - 2 tail abnormalities, 1 depressed sternum, 1 short snout were observed in 4 pups in 4 litters of Control, 2 syndactyly, renal agenesis, no sex organs (1 agnatha), 1 syndactyly and renal agenesis, 1 pup with small kidney were observed 4 pups in 2 litters of 20 mg/kg bw. Tail abnormalities were observed in 2 pups in 2 litters of 100 mg/kg bw and 1 agnatha, 2 tail abnormalities, 1 misshapen skull were observed in 4 pups in 2 litters of 500 mg/kg bw. Syndactyly and renal agenesis have been reported as a spontaneously occurring genetic syndrome in Sprague Dawley rats. Therefore, No adverse effect level (NOAEL) was considered to be 500 mg/kg for P and F1 generation when Sprague-Dawley female rats were treated with Distillates, petroleum, hydrotreated light orally by gavage for approx. 142 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 reproductive toxicity. Based on the observations Dodecanentirile does not exhibit toxicity to reproduction and hence the test chemical is not likely to classify as a toxicant for reproduction as per CLP regulation.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

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 reproductive toxicity. Based on the observations Dodecanentirile does not exhibit toxicity to reproduction and hence the test chemical is not likely to classify as a toxicant for reproduction as per CLP regulation.