Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
repeated dose toxicity: inhalation
Remarks:
combined repeated dose and reproduction / developmental screening
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from NTRL report

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 Kodak Co. (1996) Reproduction/Developmental toxicity screening test in the rat. Toxicological Sciences Laboratory, Health and Environment Laboratories. Study No. HAEL 95-0202.
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:
other: OECD:TG- 421
Principles of method if other than guideline:
Combined repeated dose repro-devp. Screen of 2-Nonanone was performed usins Sprague-Dawley rats
GLP compliance:
no
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: 2-Nonanone
- IUPAC name: nonan-2 -one
- Molecular formula: C9H18O
- Molecular weight: 142.24g/mol
- Substance type: Organic
- Physical state: Liquid
- Impurities (identity and concentrations): 99% pure

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on species / strain selection:
No data
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:
not specified
Vehicle:
air
Remarks:
Fileterd room air
Remarks on MMAD:
MMAD / GSD: No data available
Details on inhalation exposure:
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:
0, 80, 400 or 1000 ppm. (0, 80, 400 or 1000 mg/L)
Actual exposure concentrations: 0, 78.6, 405.8 or 1022.6 ppm (0, 78.6, 405.8 or 1022.6 mg/L)
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

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included: Survival was observed.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data available

BODY WEIGHT: Yes
- Time schedule for examinations: No data available

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available

FOOD EFFICIENCY: No data available
- 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: No data available

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available

OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available

HAEMATOLOGY: No data available
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available

CLINICAL CHEMISTRY: No data available
- Time schedule for collection of blood: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available

URINALYSIS: No data available
- Time schedule for collection of urine: No data available
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters checked in table [No.?] were examined. No data available

NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available

OTHER:
The testes and epididymis were also weighed
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes, The ovaries, vagina, uterus, Fallopian tubes, and testes, epididymis, and male accessory sex organs were examined histologically.
Other examinations:
No data
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.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
no mortality observed
Description (incidence):
No effects were 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
Gross pathological findings:
no effects observed
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
Clinical signs and mortality:
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 and weight gain :No effect were observed on body weight and weight gain of treated rats as compared to control

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

Compound intake:
No data available

Food efficiency: No data available

Water consumption and compound intake: No data available

Opthalmoscopic examination: No data available

Haematology: No data available

Clinical chemistry: No data available

Urinanalysis: No data available

Neurobehaviour: No data available

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.

Other: Sperm parameter:
No change in Mean sperm motility and mean epididymal spermatozoan and testicular spermatid counts were observed in treated male rats as compared to control.

Effect levels

open allclose all
Dose descriptor:
NOAEC
Remarks:
F0
Effect level:
80 mg/L air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No advarse effect on survival clinical sign, body weight and body weight gain, food consumption, sperm parameter, gross pathology and histopathology
Dose descriptor:
NOAEC
Remarks:
F1
Effect level:
1 000 mg/L air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effect on clinical signs, weight gain and gross pthology

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The No Observed Adverse effect concentration (NOAEC) was considered to be 80 ppm (80 mg/L) (actual dose 78.6 mg/L) when Sprague-Dawley male and female rats treated with 2-Nonanone
Executive summary:

In Combined repeated dose repro-devp. Screen test, Sprague Dawley male and female rats were exposed to 2 -Nonanone by inhalation in the concentration of 0, 80, 400 and 1000 ppm (0, 80, 400 or 1000 mg/L). Actual exposure concentrations is 0, 78.6, 405.8 or 1022.6 ppm (0, 78.6, 405.8 or 1022.6 mg/L) for 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 -7 in 100 mg/kg/day dose group were observed as compared to control. In addition, no effects were observed on organ weight, gross pathology, sperm parameter and histopathology of treated rats as compared to control. Therefore, the No Observed Adverse effect concentration (NOAEC) was considered to be 80 ppm (80 mg/L) (actual dose 78.6 mg/L) when Sprague-Dawley male and female rats treated with 2-Nonanone