Registration Dossier

Diss Factsheets

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
reproductive toxicity, other
Remarks:
Combined repeat dose and reproductive / developmental toxicity test
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 HPV Challenge Program

Data source

Reference
Reference Type:
secondary source
Title:
Revised Robust Summaries for Ketone Bottoms ( KB4/KB3) CAS NO. 68990-20-5, Eastman Chemical Company
Author:
Eastman Chemical Company
Year:
2007
Bibliographic source:
HPV Challenge Program, Eastman Chemical Company, 17 April 2007, page no 1-238

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
Principles of method if other than guideline:
Combined repeat dose and reproductive / developmental toxicity test of 2-Nonanone in rats
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Nonan-2-one
EC Number:
212-480-0
EC Name:
Nonan-2-one
Cas Number:
821-55-6
Molecular formula:
C9H18O
IUPAC Name:
nonan-2-one
Constituent 2
Reference substance name:
2-Nonanone
IUPAC Name:
2-Nonanone
Test material form:
other: Liquid
Details on test material:
- Name of test material (as cited in study report): 2-Nonanone
- Molecular formula (if other than submission substance): C9H18O
- Molecular weight (if other than submission substance): 142.24g/mol
- Substance type: Organic
- Physical state: Liquid
- Impurities (identity and concentrations): 99%.
Specific details on test material used for the study:
- Name of test material (as cited in study report): 2-Nonanone
- Molecular formula (if other than submission substance): C9H18O
- Molecular weight (if other than submission substance): 142.24g/mole
- Substance type: Organic
- Physical state: Liquid
- Impurities (identity and concentrations): < 1%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
No data available

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure (if applicable):
not specified
Vehicle:
air
Remarks:
Filtered room
Details on exposure:
No data available.
Details on mating procedure:
No data available.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
50 days
Frequency of treatment:
6 hours/day, 7 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 80, 400, or 1000 ppm. Actual exposure concentrations 0, 78.6, 405.8 or 1022.6 ppm (0,7.86, 40.58 and 102.26 )
Basis:
actual ingested
No. of animals per sex per dose:
No data available.
Control animals:
yes, concurrent vehicle
Details on study design:
No data available.
Positive control:
No data available.

Examinations

Parental animals: Observations and examinations:
Survival, Clinical sign, Body weight and food consumption were observed.
Oestrous cyclicity (parental animals):
No data available
Sperm parameters (parental animals):
Analysis of epididymal spermatozoan numbers and motility, and testicular spermatid head countswere determined.
Litter observations:
Live pups, Clinical signs and weight gain were observed.
Postmortem examinations (parental animals):
Organ weight, gross pathology and histopathology were observed.
Postmortem examinations (offspring):
Abnormalities were observed.
Statistics:
Homogeneity of data were evaluated by Bartlett's test (p, 0.01), analysis of variance (ANOVA, <0.05), and Dunnett's test (p, 0.05). When the variances of the means were not considered equal by Bartlett's test, the data were evaluated by Kruskal-Wallis H-test (p, 0.05) followed by Mann-Whitney U-test (p<0.05). The reproductive performance of dams and fertility and fecundity indices were evaluated in contingency tables, using Chi-square test (p,0.05). The total number of pups per litter (live and dead) and the total number of live pups per litter were evaluated by a linear regression model.
Reproductive indices:
Fertility and fecundity indices were observed.
Offspring viability indices:
The total number of pups per litter (live and dead) and the total number of live pups per litter were evaluated

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
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:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
not specified

Details on results (P0)

Mortality: No effect on survival of treated rats was observed as compared to control.

Clinical sign: Minimal reductions in activity level were observed in 40 and 100 mg/kg/day dose group.
No other abnormalities were observed in treated rats as compared to control.

Body weight: No effects were observed on body weight and weight gain of treated rats as compared to control.

Food consumption: In male rats, reduction in food consumption during days 0-7 hen treated with 100 mg/kg/day as compared to control.

Reproductive function: sperm measures: No change in mean sperm motility and mean epididymalspermatozoan and testicular spermatid counts were observed in treated male rats as compared to control.

Organ weights: No effect was observed on organ weight of treated rats as compared to control.

Gross pathology: No gross pathological changes were observed in treated rats as compared to control.

Histopathology: No histopathological changes in organs were observed in treated rats as compared to control.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
7.86 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant effect were observed on Reproductive organ
Remarks on result:
other: No effect were observed on Reproductive organ

Target system / organ toxicity (P0)

Critical effects observed:
not specified

Results: P1 (second parental generation)

General toxicity (P1)

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
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
no effects observed
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:
no effects observed
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Details on results (F1)

Clinical signs:No clinical sign were obsserved in pups as compare to control.

Body weight : No body weight gain were obsserved in pups as compare to control.

Gross pathology: No abnormalities were observed in pups as compared to control.

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
102.26 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
body weight and weight gain
gross pathology
Remarks on result:
other: No effect were observed on Reproductive organ

Target system / organ toxicity (F1)

Critical effects observed:
not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F2 generation

General toxicity (F2)

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

Developmental neurotoxicity (F2)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F2)

Developmental immunotoxicity:
not specified

Overall reproductive toxicity

Reproductive effects observed:
no
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 80 ppm (8 mg/kg/day) (actual dose 7.86 mg/kg/day)for P generation and 1000 ppm (100 mg/kg) (actual dose 102.26 mg/kg/day) for F1 generation when Sprague-Dawley male and female rats treated with 2-Nonanone by Inhalation.
Executive summary:

In Combined repeated dose repro-devp. Screen test,Sprague-Dawleymale and female rats exposed to 2-Nonanoneby inhalation in the concentration of 0, 80, 400 and 1000 ppm. (0, 7.86, 40.58 and 102.26 mg/kg/day) Actual exposure concentrations is 0, 78.6, 405.8 and 1022.6 ppm (0,7.86, 40.58 and 102.26 mg/kg/day) 6 hours/day, 7 days/week for 50 days. No effect on survival,Body weight and weight gain were observed in treated rats as compared to control.Minimal reductions in activity level were observed in 40 and 100 mg/kg/day dose group andreduction in food consumption during days 0-7in 100 mg/kg/day dose groupwere observed as compared to control. In addition, no effects were observed on organ weight, gross pathology,Sperm parameterand histopathology of treated rats as compared to control. Similarly, no effects were observed on clinical sign, body weight gain and gross pathology of pups as compared to control. Therefore, NOAEL was considered to be80 ppm(8 mg/kg/day) (actual dose 7.86 mg/kg/day)for P generation and1000 ppm (100 mg/kg) (actual dose 102.26 mg/kg/day) for F1 generation whenSprague-Dawleymale and female rats treated with2-Nonanoneby inhalation6 hours/day, 7 days/week for 50 days.

Categories Display