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Description of key information

Repeated dose toxicity: Oral

The 90 days feeding study in rats has been carried out on the test chemical. 15 male and 15 female rats were given diets containing the test chemical for 90 days at concentrations reported to result in daily intakes of 33 mg/kg bw per day for males and 37 mg/kg bw per day for females. Different parameters like body weight and food consumption, haematologieal and blood chemical determinations were made on 8 rats of each sex at a 6-wk period, and in all rats at 12 wk. The tests were terminated at 90 days and at autopsy, liver and kidney weights were recorded and thefollowing organs from half the animals in each group were taken for histological examination. Measurements of growth, haematological and clinical chemical end-points, and gross and histological examination at necropsy revealed no significant adverse effects. Thus from above results it can concluded that the NOAEL (no observed adverse effect level ) of the test chemical was considered to be 33 mg/kg bw per day for males and 37 mg/kg bw per day for females.

Repeated dose toxicity: Inhalation

2'-acetonaphthone (CAS no 93-08-3) has very low vapor pressure of 0.000395 mm Hg at 21.9°C. 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. Also, the particle size distribution was determined in the range of 500 micrometer to 1000 micron.Therefore this end point for repeated dose toxicity by inhalation route is considered for waiver.

Repeated dose toxicity: Dermal

The acute dermal toxicity value for2'-acetonaphthone (CAS no 93-08-3)(as provided in section 7.2.3) is >2000 mg/kg body weight. Considering this, the end point for repeated dermal toxicity is considered as waiver

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:
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 publication
Qualifier:
according to
Guideline:
other: Refer below principle
Principles of method if other than guideline:
Repeated dose toxcity of the test chemical was performed to determine the toxic nature of the test chemical upon repeated exposure by oral route.
GLP compliance:
not specified
Species:
rat
Strain:
other: FDRL
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation:
- Fasting period before study:
- Housing:housed individually in wiremesh cages
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:

Route of administration:
oral: feed
Vehicle:
cotton seed oil
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with cotton seed oil to give dose level of 0, 33 mg/Kg/day (males) and 37 mg/Kg/day (females)

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

VEHICLE
- Justification for use and choice of vehicle (if other than water): Cottonseed oil
- Concentration in vehicle: 0, 33 mg/Kg/day (males) and 37 mg/Kg/day (females)
- 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
Duration of treatment / exposure:
90 days
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
0.0, 33 ( for males) and 37 ( for females) mg/kg bw per day
Basis:
no data
No. of animals per sex per dose:
15 male and 15 female rats
Control animals:
yes, plain diet
Details on study design:
No data
Positive control:
No data
Observations and examinations performed and frequency:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:

BODY WEIGHT: Yes
- Time schedule for examinations:

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

FOOD EFFICIENCY:
- 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

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

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

HAEMATOLOGY: Yes
- Time schedule for collection of blood:on 8 rats of each sex at a 6-wk period, and in all rats at 12 wk
- Anaesthetic used for blood collection: Yes (identity) / No / No data
- Animals fasted: Yes / No / No data
- How many animals:15
- Parameters checked in table [No.?] were examined.

CLINICAL CHEMISTRY: Yes / No / No data
- Time schedule for collection of blood:on 8 rats of each sex at a 6-wk period, and in all rats at 12 wk
- Animals fasted: Yes / No / No data
- How many animals:15
- Parameters checked in table [No.?] were examined.

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

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

OTHER:
Sacrifice and pathology:
The tests were terminated at 90days and at autopsy, liver and kidney weights were recorded and thefollowing organs from half the animals in each group were taken for histological examination: liver, kidneys, stomach, small and large intestines, spleen, pancreas, heart, lungs, bone marrow, muscle, brain, spinal cord, bladder, adrenals, thyroid, pituitary, gonads, salivary glands, and lymph nodes.
Other examinations:
No data
Statistics:
No data
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
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:
no effects observed
Other effects:
not specified
Details on results:
-Measurements of growth, haematological and clinical chemical end-points, and gross and histological examination at necropsy revealed no significant adverse effects

-No significant gross pathological change was observed at autopsy in any of the rats in this study
Dose descriptor:
NOEL
Effect level:
33 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Measurements of growth, haematological and clinical chemical end-points, and gross and histological examination at necropsy revealed no significant adverse effects
Dose descriptor:
NOEL
Effect level:
37 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Measurements of growth, haematological and clinical chemical end-points, and gross and histological examination at necropsy revealed no significant adverse effects
Critical effects observed:
not specified
Conclusions:
The NOAEL (no observed adversed effect level ) of the test chemical was considered to be 33 mg/kg bw per day for males and 37 mg/kg bw per day for females

Executive summary:

The 90 days feeding study in rats has been carried out on the test chemical. 15 male and 15 female rats were given diets containing the test chemical for 90 days at concentrations reported to result in daily intakes of 33 mg/kg bw per day for males and 37 mg/kg bw per day for females. Different parameters like body weight and food consumption, haematologieal and blood chemical determinations were made on 8 rats of each sex at a 6-wk period, and in all rats at 12 wk. The tests were terminated at 90 days and at autopsy, liver and kidney weights were recorded and thefollowing organs from half the animals in each group were taken for histological examination. Measurements of growth, haematological and clinical chemical end-points, and gross and histological examination at necropsy revealed no significant adverse effects. Thus from above results it can concluded that the NOAEL (no observed adverse effect level ) of the test chemical was considered to be 33 mg/kg bw per day for males and 37 mg/kg bw per day for females.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
33 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
K2 level data

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: inhalation
Data waiving:
exposure considerations
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Waiver

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: dermal
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Waiver

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Data available for the test chemicals was reviewed to determine the toxic nature upon repeated exposure. The studies are as mentioned below:

Repeated dose toxicity: Oral

The 90 days feeding study in rats has been carried out on the test chemical. 15 male and 15 female rats were given diets containing the test chemical for 90 days at concentrations reported to result in daily intakes of 33 mg/kg bw per day for males and 37 mg/kg bw per day for females. Different parameters like body weight and food consumption, haematologieal and blood chemical determinations were made on 8 rats of each sex at a 6-wk period, and in all rats at 12 wk. The tests were terminated at 90 days and at autopsy, liver and kidney weights were recorded and thefollowing organs from half the animals in each group were taken for histological examination. Measurements of growth, haematological and clinical chemical end-points, and gross and histological examination at necropsy revealed no significant adverse effects. Thus from above results it can concluded that the NOAEL (no observed adverse effect level ) of the test chemical was considered to be 33 mg/kg bw per day for males and 37 mg/kg bw per day for females.

In a 28 days repeated dose toxicity study, the effect of the test chemical was evaluated in male and female Sprague Dawley rats. The test chemical was administered by oral gavage in the concentration of 0, 125, 250 or 500 mg/kg body weight/day. 2 animals died at 500 mg/kg bw as compared to control.Abnormalities such as nasal discharge, red crust around the nostrils was observed in all treatment groups. In addition, a few cases of snuffling, eye lid swelling and hunched back posture were also observed in the treated groups. A significant decrease in body weights in male rats on the first, second and fourth week of treatment and in female rats, a significant decrease in body weight was observed on the first, second and third week of treatment were observed as compared to control. No effects on food and water consumption were observed as compared to control. In addition, In hematology, the test chemical resulted in significantly increased platelet count along with decreased MCV, MCH and MCHC levels. Treatment with 250 mg/kg body weight/day resulted in significantly decreased levels of hemoglobin and MCHC in male rats. At 250 mg/kg body weight/day, a significant decrease was noticed in neutrophils along with altered values of MCV in female rats. In clinical chemistry, significantly increased the level of testosterone in the 500 mg/kg body weight/day group in males, as well as it significantly increased the level of estrogen in the 250 mg/kg body weight/day group in females. Significant increased levels in cholesterol, potassium and albumin was also observed. Similarly, Changes in relative and absolute organ weight of spleen, kidney, liver, brain, heart, ovaries and uterus were observed when treated with 125, 250 or 500 mg/kg body weight/day. Nasal discharge, red crust around nostril, perineum wet, bloated stomach, viscous oily secretion was found inside the thoracic cavity. Small white solid mass slightly firm in consistency floating inside the urinary bladder was observed. However, due to adaptive metabolic and physiological changes, anoxic/ hypoxic conditions during anesthesia and terminal sacrifice, these findings were considered to be of no toxicological significance. No remarkable changes observed in control and the 500 mg/kg body weight/day-treated animals. A few microscopic findings observed in 500 mg/kg body weight/day-treated animals included collapsed lung with focal inflammation, focal fatty change and excess of lymphocytes in liver, inflammation in small intestine, reactive spleen and excess of mucous in colon. Since the histopathological changes were not observed in 125 mg/kg bw and these findings were also observed in the control animals. Hence, NOAEL was considered to be 125 mg/kg bw and LOAEL was considered to be 250 mg/kg body weight/day when Sprague Dawley male and female rats were exposed daily to the test chemical by oral route for 28 days.

Groups of 10 male and 10 female Sprague-Dawley rats were exposed to 0, 75, 225 and 750 mg test chemical/kg bw/day for >46 days by daily gavage application. Different parameters like clinical signs, body weight development and food consumption were examined. Blood samples were collected on the day of scheduled euthanasia (study day 33 or 34) for evaluation of selected hematology, coagulation and clinical chemistry parameters.A dose-related increase in total protein, albumin and globulin appeared to correlate with a dose-related increase in liver weight. Thus no observed adverse effect level (NOAEL) for the test chemical is considered to be 225 mg/Kg/day.

Repeated dose toxicity: Inhalation

2'-acetonaphthone (CAS no 93-08-3) has very low vapor pressure of 0.000395 mm Hg at 21.9°C. 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. Also, the particle size distribution was determined in the range of 500 micrometer to 1000 micron.Therefore this end point for repeated dose toxicity by inhalation route is considered for waiver.

Repeated dose toxicity: Dermal

The acute dermal toxicity value for2'-acetonaphthone (CAS no 93-08-3)(as provided in section 7.2.3) is >2000 mg/kg body weight. Considering this, the end point for repeated dermal toxicity is considered as waiver

Based on the data available for the test chemical and applying the weight of evidence approach, the test chemical does not exhibit toxicity upon repeated exposure by oral, inhalation and dermal route of exposure. Hence the test chemical is not likely to classify as a toxicant as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the test chemical and applying the weight of evidence approach, the test chemical does not exhibit toxicity upon repeated exposure by oral, inhalation and dermal route of exposure. Hence the test chemical is not likely to classify as a toxicant as per the criteria mentioned in CLP regulation.