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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

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from peer-reviewed journal.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
RIFM fragrance ingredient safety assessment - Test chemical
Author:
Api et al.
Year:
2017
Bibliographic source:
Food and Chemical Toxicology
Reference Type:
other: Secondary source
Title:
Repeated dose oral toxicity study of the test chemical
Author:
USEPA
Year:
2019
Bibliographic source:
HPVIS

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OTS 798.2650 (90-Day Oral Toxicity in Rodents)
Principles of method if other than guideline:
Repeated dose oral toxicity study was performed to determine the toxic effects of the test chemical.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Acetic acid, C7-9-branched alkyl esters, C8-rich
Cas Number:
108419-32-5
Molecular formula:
C10H20O2
IUPAC Name:
Acetic acid, C7-9-branched alkyl esters, C8-rich
Details on test material:
- Name of test material (as cited in study report):Acetic acid, C7-9-branched alkyl esters, C8-rich
- Molecular formula (if other than submission substance):C10H20O2
- Molecular weight (if other than submission substance):172.266 g/mole
- Substance type:Organic
- Physical state:Liquid
- Purity:>90%

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

Administration / exposure

Route of administration:
oral: gavage
Details on route of administration:
No data
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100, 500, and 1000 mg/kg/day
- Amount of vehicle (if gavage): 1.111 ml/kg
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
90 Days
Frequency of treatment:
daily, 5 days/week for 13 weeks
Doses / concentrationsopen allclose all
Dose / conc.:
0 other: mg/kg/day
Remarks:
Control
Dose / conc.:
100 mg/kg bw/day (nominal)
Dose / conc.:
500 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
A group of 20 rats/sex/group
Control animals:
yes, concurrent vehicle
Details on study design:
No data
Positive control:
No data

Examinations

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

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

BODY WEIGHT: Yes, all surviving animals were weighed.
- Time schedule for examinations: after 13 weeks

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

HAEMATOLOGY: Yes, blood samples were collected from the abdominal aortas.
- Time schedule for collection of blood: following an overnight fast
- Anaesthetic used for blood collection: No data
- Animals fasted: Yes
- How many animals: No data
- Parameters checked in table [No.?] were examined.

CLINICAL CHEMISTRY: Yes, clinical laboratory studies (hematology and serum chemistry) were
Performed.
- Time schedule for collection of blood: after 45 days and at study termination.
- Animals fasted: No data
- How many animals: on 5
animals/sex/dose after 45 days (interim sacrifice), and all animals at study termination.
- Parameters checked in table [No.?] were examined.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, at 45 days, a complete necropsy was performed and livers were collected, weighed and reserved. After 13 weeks, all surviving animals were weighed, anesthetized and sacrificed by exsanguination. Complete necropsies were performed.
HISTOPATHOLOGY: Yes, microscopic examination was performed.
Other examinations:
No data
Statistics:
No data

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Rats produced minimal signs of systemic toxicity.
Mortality:
no mortality observed
Description (incidence):
There was no treatment-related mortality.
Body weight and weight changes:
effects observed, non-treatment-related
Description (incidence and severity):
Weekly mean body weights were not significantly altered compared to controls.
Food consumption and compound intake (if feeding study):
effects observed, non-treatment-related
Description (incidence and severity):
Food consumption values were not significantly altered compared to controls.
Food efficiency:
not specified
Description (incidence and severity):
No data
Water consumption and compound intake (if drinking water study):
not specified
Description (incidence and severity):
No data
Ophthalmological findings:
not specified
Description (incidence and severity):
No data
Haematological findings:
no effects observed
Description (incidence and severity):
The qualitative hematologic data were unremarkable at all dose levels for the interim and terminal evaluations.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
At the terminal sacrifice, there were no biologically significant differences between treated and control animals for the measured clinical chemistries.
Urinalysis findings:
not specified
Description (incidence and severity):
No data
Behaviour (functional findings):
not specified
Description (incidence and severity):
No data
Immunological findings:
not specified
Description (incidence and severity):
No data
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Description (incidence and severity):
Terminal liver and kidney weights were elevated in a dose-related manner but were considered to be adaptive changes and not indicative of toxic effects. All other organ weights were comparable to control values.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Microscopic evaluation of the kidneys showed evidence of mild tubular nephropathy only in the high-dose male rats that were consistent with alpha-2u-globulin effects.
Neuropathological findings:
not specified
Description (incidence and severity):
No data
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
Histopathology review of all other tissues from high-dose animals, including reproductive organs (testes, epididymides, prostate, seminal vesicles, ovaries, uterine horns, cervix, and corpus of the uterus, and vagina), showed normal morphology.
Histopathological findings: neoplastic:
not specified
Description (incidence and severity):
No data
Other effects:
not specified
Description (incidence and severity):
No data

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
clinical biochemistry
clinical signs
food consumption and compound intake
gross pathology
haematology
histopathology: non-neoplastic
mortality
organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The No Observed Adverse Effect Level (NOAEL) was considered to be 1000 mg/kg bw/day, when male and female Sprague-Dawley rats were exposed to the given test chemical for 90 days.
Executive summary:

90 days repeated oral toxicity study was performed to determine the toxic nature of the given test chemical. The study was performed using male and female Sprague-Dawley rats at dose level of 0 (water) or 100, 500 or 1000 mg/kg/day. Controls received a dose of water volumetrically comparable to the dosage administered to the high dose group, 1.111 ml/kg. Clinical laboratory studies (hematology and serum chemistry) were performed pretest on 5 males and 5 females (non-study animals), on 5 animals/sex/ dose after 45 days (interim sacrifice), and all animals at study termination. Blood samples were collected from the abdominal aortas following an overnight fast. At 45 days, a complete necropsy was performed and livers were collected, weighed and preserved. After 13 weeks, all surviving animals were weighed, anesthetized and sacrificed by exsanguination. Complete necropsies were performed.

Oral administration of the test chemical daily, 5 days/week for 13 weeks, to rats produced minimal signs of systemic toxicity. There was no treatment-related mortality. The in-life clinical observations were primarily oral and dermal irritation (no clear dose response). Weekly mean body weights and food consumption values were not significantly altered compared to controls. The qualitative hematologic data were unremarkable at all dose levels for the interim and terminal evaluations. At the terminal sacrifice, there were no biologically significant differences between treated and control animals for the measured clinical chemistries. Terminal liver and kidney weights were elevated in a dose-related manner but were considered to be adaptive changes and not indicative of toxic effects. All other organ weights were comparable to control values. Microscopic evaluation of the kidneys showed evidence of mild tubular nephropathy only in the high-dose male rats that were consistent with alpha-2u-globulin effects. Histopathology review of all other tissues from high-dose animals, including reproductive organs (testes, epididymides, prostate, seminal vesicles, ovaries, uterine horns, cervix, and corpus of the uterus, and vagina), showed normal morphology.

Based on the results of the study, the No Observed Adverse Effect Level (NOAEL) was considered to be 1000 mg/kg bw/day, when male and female Sprague-Dawley rats were exposed to the given test chemical for 90 days.