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Description of key information

Repeated dose toxicity: Oral

The No Observed Adverse Effect Level (NOAEL) for test substance was considered  to be <100 mg/Kg bw/ day in male rats.

Repeated dose toxicity: Inhalation

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance methyl 1-naphthyl ketone (941-98-0) which is reported as 0.0003922823 mmHg at 25 C. Thus, exposure to inhalable dust, mist and vapour of the chemical methyl 1-naphthyl ketone is highly unlikely. Therefore this study is considered for waiver.

Repeated dose toxicity: Dermal

The No Observed Adverse Effect level (NOAEL) for test chemical  was  considered to be 0.5mL (557.2 mg/kg) when applied to the clipped backs of guinea pigs.

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: oral, other
Type of information:
experimental study
Adequacy of study:
key study
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 monograph
Qualifier:
according to guideline
Guideline:
other: Refer below principle
Principles of method if other than guideline:
Reproductive toxicity study was conducted for test chemicals in rats
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
not specified
Details on species / strain selection:
No data
Sex:
not specified
Details on test animals or test system and environmental conditions:
No data
Route of administration:
oral: feed
Details on route of administration:
No data
Vehicle:
other: Feed
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: α-methyl naphthyl ketone was mixed with feed to give a dose range of 3, 10, 60 or 100 mg/Kg

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Feed
- Concentration in vehicle: 3, 10, 60 or 100 mg/Kg
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
No data
Frequency of treatment:
No data
Remarks:
3, 10, 60 or 100 mg/Kg
No. of animals per sex per dose:
No data
Control animals:
not specified
Details on study design:
No data
Positive control:
No data
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included. Growth

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

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

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data available
- 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
- 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: Yes
- Time schedule for collection of blood: No data available
- Animals fasted: Yes
- How many animals: No data available
- Parameters checked in table [No.?] were examined. Hepatic protein content, hepatic nitrogen content, ascorbic acid content of adrenal glands

URINALYSIS: No data
- 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: No data available
Sacrifice and pathology:
No data
Other examinations:
No data
Statistics:
No data
Clinical signs:
no effects observed
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:
no effects observed
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:
No data
Dose descriptor:
NOAEL
Effect level:
100 mg/kg diet
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: No alterations noted at the mentioned dose level
Remarks on result:
other: No toxic effects were observed
Critical effects observed:
not specified
Conclusions:
The No Observed Adverse Effect Level (NOAEL) for test chemical was considered to be 100 mg/Kg bw/ day in rts for
Executive summary:

Repeated dose toxicity study was conducted on rats for the test compound at the dosage levels of 3, 10, 60 or 100 mg/Kg bw/day.  The animals were observed for clinical signs and clinical chemistry changes. No influence on the rate of hepatic protein recovery after fasting, on the hepatic nitrogen content, on the ascorbic acid content of the adrenal glands or on blood chemistry was noted. With oral doses of 3 or 10mg given every other day, growth was not significantly towered in rats fed 11 or 19% protein diets. Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for test chemical was considered to be 100 mg/Kg bw/ day.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Data is from K2 publication

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
1- Acetonaphthone has very low vapor pressure, so the potential for the generation of inhalable vapours is very low, also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point has been considered for waiver

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
557.2 mg/kg bw/day
Study duration:
subacute
Species:
rabbit
Quality of whole database:
Data is from from handbook or collection of data.

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The data available for the test chemical was reviewed to determine the toxic nature of methyl 1-naphthyl ketone (941-98-0)repeated exposure by oral route. The study is as mentioned below:

Repeated dose toxicity: via oral route;

Repeated dose toxicity study was conducted on rats for the test compound at the dosage levels of 3, 10, 60 or 100 mg/Kg bw/day.  The animals were observed for clinical signs and clinical chemistry changes. No influence on the rate of hepatic protein recovery after fasting, on the hepatic nitrogen content, on the ascorbic acid content of the adrenal glands or on blood chemistry was noted. With oral doses of 3 or 10mg given every other day, growth was not significantly towered in rats fed 11 or 19% protein diets. Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for test chemical was considered to be 100 mg/Kg bw/ day.

Supported by other repeated dose toxicity study. Repeated dose toxicity study was conducted on male rats for the test chemical at the dosage levels of 100, 500 and 1000 mg/Kg bw/day. Controls received 1000 mg/Kg of distilled water. Clinical signs, mortality, body weight, organ weight hematological and clinical chemistry changes were noted and gross pathology and histopathology was performed. The 1000 mg/Kg bw/day dose severely affected food intake and body weight gain. Anormalities like greatly increased liver and slightly increased kidney weights, necrotic and hemorrhagic changes of the gastrointestinal tract, hemorrhaging in the urinary bladder, and blood in the urine were noted in 1000 mg/Kg bw/day group. Necrosis and edema of the gastrointestinal tract, acute hepatitis, kidney congestion with tubular casts, tubular dilatation and hydropic changes in proximal tubular epithelium, vacuolization of adrenal medulla, decrease in number and/or degeneration of spermatids and spermatozoa, bobe marrow congestion, thymic necrosis, and exfoliation of epithelial cells was noted. Moderate decrease in body weight gain in 500 mg/Kg bw/day and a slight to moderate increase in absolute liver weights in the 500 and 1000 mg/Kg bw/day dose groups was noted and the only other treatment related changes in the lower two dose groups were hepatocyte hypertrophy and hyaline droplet formation in the kidneys. Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for test chemical was considered to be <100 mg/Kg bw/ day.

Repeated inhalation study:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance methyl 1-naphthyl ketone (941-98-0) which is reported as 0.0003922823 mmHg at 25 C. Thus, exposure to inhalable dust, mist and vapour of the chemical methyl 1-naphthyl ketone is highly unlikely. Therefore this study is considered for waiver.

Repeated dermal study;

Repeated dose dermal toxicity study was performed to determine the dermal toxic nature of test chemical. Uncovered application of 0.5mL (557.2 mg/kg) of the test compound was applied daily for 10 days to the clipped backs of 5 guinea pigs. The animals were observed for dermal irritation. Slight exacerbation was noted upon repeated application. Slight erythema was noted in 4/5 guinea pigs on day 1 and slight to moderate erythema in 5/5 and edema and/or vesicles in 4/5 guinea pigs after 2 weeks. However, the report mentions no percutaneous absorption at 20mL/Kg dose (22288 mg/Kg bw/day) in acute dermal toxicity study performed. Since the no percuteaneous absorption acute dermal dose of 22288 mg/Kg bw/day is greater than the repeated dose dermal toxicity dose (557.2 mg/Kg bw) and hence on this basis, the No Observed Adverse Effect level (NOAEL) for 1- Acetonaphthalene is considered to be 0.5mL (557.2 mg/kg) when applied to the clipped backs of guinea pigs.

Based on the data available for the test chemical methyl 1-naphthyl ketone (941-98-0) does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data summarized, 1- Acetonaphthone (CAS no 941 -98 -0; IUPAC name: 1-(1-naphthyl)ethanone) is not likely to exhibit repeated dose oral and dermal toxicity. Hence the chemical is not likely to classify as a toxicant upon repeated exposure by oral and dermal route of exposure as per the criteria mentioned in CLP regulation.

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