Dodecanenitrile

Repeated dose toxicity: oral

Administrative data

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.

Data source

Reference

Reference Type:

secondary source

Title:

Reproductive toxicity of CAS no 2437-25-4

Author:

TSCA

Year:

2006

Bibliographic source:

US Environmental Protection Agency, TSCA, June 12,2006,

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Dodecanenitrile

EC Number:

219-440-1

EC Name:

Dodecanenitrile

Cas Number:

2437-25-4

Molecular formula:

C12H23N

IUPAC Name:

dodecanenitrile

Test material form:

liquid

Details on test material:

- Name of test material (IUPAC name): Dodecanenitrile
- Molecular formula: C12H23N
- Molecular weight: 181.321 g/mole
- Smiles notation: C(CCCCCC)CCCCC#N
- InChl: 1S/C12H23N/c1-2-3-4-5-6-7-8-9-10-11-12-13/h2-11H2,1H3
- Substance type: Organic
- Physical state: colourless liquid

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

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Administration / exposure

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

Doses / concentrations

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.

Examinations

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.

Results and discussion

Results of examinations

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.

Effect levels

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

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

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.