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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
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:
other: OECD:TG- 421
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
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.
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
No data available
Duration of treatment / exposure:
50 days
Frequency of treatment:
6 hours/day, 7 days/week
Duration of test:
Males were exposed for 50 days; females were exposed for 34-47 days (through day 19 of gestation)
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 mg/kg/day)

No. of animals per sex per dose:
No data available.
Control animals:
yes, concurrent vehicle
Details on study design:
No data available.

Examinations

Maternal examinations:
Survival, Clinical sign, Body weight, food consumption, Sperm parameter, Organ weight, gross pathology and histopathology were observed.
Ovaries and uterine content:
No data available
Fetal examinations:
Live pups, Clinical signs and body weight gain and 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.
Indices:
Fertility and fecundity indices were observed.
Historical control data:
No data available

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

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
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

Maternal developmental toxicity

Number of abortions:
not specified
Pre- and post-implantation loss:
not specified
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
not specified
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
not specified
Other effects:
not specified
Details on maternal toxic effects:
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.

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 (maternal animals)

Dose descriptor:
NOAEL
Effect level:
1 000 ppm
Based on:
test mat.
Basis for effect level:
body weight and weight gain
gross pathology
histopathology: non-neoplastic
mortality
organ weights and organ / body weight ratios
other: Sperm measures:

Maternal abnormalities

Abnormalities:
not specified
Localisation:
not specified

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Reduction in number of live offspring:
not specified
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
no effects observed
Skeletal malformations:
not specified
Visceral malformations:
not specified
Other effects:
not specified
Details on embryotoxic / teratogenic effects:
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 (fetuses)

Dose descriptor:
NOAEL
Effect level:
102.26 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
fetal/pup body weight changes
external malformations
other: No advease effect on clinical signs

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified
Treatment related:
not specified
Relation to maternal toxicity:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

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

In a Combined repeated dose repro-devp. Screentest,Sprague-Dawleymale and female rats exposed to2-Nonanoneby inhalation in the concentration of0, 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/weekfor 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/daydose 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 be 8 mg/kg/day (actual dose 7.86 mg/kg/day) for P generation and 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/weekfor 50 days.