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REACH

Oxacycloheptadec-10-en-2-one

EC number: 249-120-7 | CAS number: 28645-51-4

Life Cycle description
Uses advised against

Toxicological information

Endpoint summary

Administrative data

Description of key information

Repeated dose toxicity - via oral route:

A repeated dose 28-day oral toxicity study was performed to determine the toxic profile ofthe test chemical when administered daily for 28 consecutive days for Sprague-Dawley rats. The test substance was administered to rats at dose levels of0 (vehicle control), 250, 500 and 1000 mg/kg body weight/day. Two additional doseswere added to the study as control (0 mg/kg/day) and 1000 mg/kg/day in order to study delayed toxiceffects orreversibilityy. The control animals were administered with corn oil. All treated animals were survived through the dosing period of 28-day and the recovery period of 14-days. No sign of toxicity was noted throughout the dosing and recovery periods. Treated rats exhibited normal body weight gain and the food consumption, which were comparable with controls. Detailed clinical observation conducted weekly did not reveal any abnormalities at any dose during the dosing and recovery periods. Ophthalmoscopic examination, conducted prior to and after the dosing period did not reveal any abnormalities.At the end of administration period, in week 4^thfunctional observation battery was performed to assess sensory reactivity to diverse stimulus, grip strength and motor activity. This functional observational battery did not reveal any differences between treated and control rats.Haematological analysis was carried out on termination days (day 29 and 43) and it did not reveal any abnormalities. In clinical biochemistry the total protein level, which reflectsthetotal amount of albumin and globulin, was significantly decreased at 500 and 1000 mg/kg/day in males and at 500 mg/kg/day in females. Creatinine concentration dropped significantly at the top dose in males, but no similar changes were seen in females. In females the alanine transaminase (ALT) and alkaline phosphatase (ALP) levels, which are indicators of liver function dropped significantly at 250, and 500 mg/kg/day, and theALTlevelin serumremained reduced at day 43. However, no similar effects on serum liver enzymes concentration was seen in male rats. In summary, no conclusive and dose-dependent alteration of serum parameters were revealed, the observed increase/decrease in concentrations were marginal and within the normal laboratory and biological limits.At the end of dosing period of 28-day, the relative weight of kidney and adrenals decreased significantly at 1000 mg/kg/day as compared to control, but no similar effect was noted among females. At the termination of recovery period (at day 43) the relative weight of liver, kidney and spleen increased significantly in both males and females. Although significant changes in organ weight were observed in male and female rats in different dose group, no related gross pathological and histopathological finding were seen and therefore, these finding were considered to be of no toxicological importance. Gross pathological and histopathological observation of organs did not reveal abnormalities at any dose level in both sexes. In conclusion, the repeated oral exposure tothe test chemicaldid notinduced toxicologically significant and severe alterations of the function or morphology of a specific tissue/organ, neither produced serious changes to the biochemistry or haematology of animalswhen SD rats were orally administered for 28 consecutive days followed by a 14-day recovery period.

Repeated dose toxicity - via inhalation route:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Considering the low vapour pressure of the substance oxacycloheptadec-10-en-2-one (28645-51-4) which is reported as 2.2351839 10^-5Hgmm at 25°C. Thus, exposure to inhalable dust, mist and vapour of the chemical oxacycloheptadec-10-en-2-one is highly unlikely and therefore this study is considered for waiver.

Repeated dose toxicity - via dermal route:

The acute toxicity value for oxacycloheptadec-10-en-2-one (28645-51-4) (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that oxacycloheptadec-10-en-2-one shall not exhibit toxic effects via dermal exposure after exposure of 28 consecutive days. In addition, there is no data available that suggests that oxacycloheptadec-10-en-2-one shall exhibit repeated dose toxicity via dermal route and, consequently this endpoint was considered for 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:: short-term repeated dose toxicity: oral
Type of information:: experimental study
Adequacy of study:: key study
Reliability:: 1 (reliable without restriction)
Rationale for reliability incl. deficiencies:: guideline study
Justification for type of information:: Data is from study report
Qualifier:: according to guideline
Guideline:: OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Principles of method if other than guideline:: To assess toxicological profile of test chemical, to determine target organ of toxicity, its reversibility and No Observed Adverse Effect Level (NOAEL) in the rat after 28 consecutive days of oral administration.
GLP compliance:: yes
Limit test:: no
Species:: rat
Strain:: Sprague-Dawley
Sex:: male/female
Details on test animals or test system and environmental conditions:: TEST ANIMALS
- Source:National Institute of Biosciences
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: (P) x wks; (F1) x wks: 6 to 8 weeks
- Weight at study initiation: (P) Males: x-x g; Females: x-x g; (F1) Males: x-x g; Females: x-x g: Male - 165.53 g (= 100 %) and Female - 150.64 g (= 100 %)
- Fasting period before study:
- Housing: The rats were housed in polycarbonate cages with paddy as bedding.
After allocation to respective dose groups rats were housed 2/sex/cage.
Identified by the picric acid marking. A group of animals in one cage was additionally identified by the label affixed to each cage. A label according to groups identified the cage and each label contained information on cage and study number. It also bear species, strain, sex and identification numbers of rats within it.
- Use of restrainers for preventing ingestion (if dermal): yes/no
- Diet (e.g. ad libitum): Rodent feed, ad libitum from individual feeders on cage top
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. Water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period:5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C (actual range, 20.0 °C to 21.9 °C)
- Humidity (%):30% to 70% (actual range, 47.0% to 59.7%).
- Air changes (per hr): at least ten air changes per hour of 100% fresh air that has been passed through the HEPA filters.
- Photoperiod (hrs dark / hrs light):An artificial light and dark cycle of 12 hours each was provided to the room.

IN-LIFE DATES:
From: 29-11-2017
To:26-2-2018
Route of administration:: oral: gavage
Vehicle:: corn oil
Details on oral exposure:: PREPARATION OF DOSING SOLUTIONS: The test item was diluted with corn oil for preparation of solution(s).
The solution(s) of test chemical were made at volumes suitable for daily use for 28 days. The solution(s) were prepared at concentrations of 0, 25, 50 and 100 mg/ml such that dosage of 0 (vehicle), 250, 500 and 1000 mg/kg body weight respectively were administered. The concentration of the test item was varied so as to maintain the dose volume constant at or upto 10 ml/kg body weight.

DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food:

VEHICLE
- Justification for use and choice of vehicle (if other than water): 0 (vehicle), 250,500 and 1000 mg/kg body weight
- Concentration in vehicle: Corn oil
- Amount of vehicle (if gavage): 10 ml/kg body weight
- Lot/batch no. (if required):
- Purity:
Analytical verification of doses or concentrations:: yes
Details on analytical verification of doses or concentrations:: Stability by UV analysis
Duration of treatment / exposure:: 28 days
Frequency of treatment:: Daily
Dose / conc.:: 0 mg/kg bw/day (actual dose received)
Dose / conc.:: 250 mg/kg bw/day (actual dose received)
Dose / conc.:: 500 mg/kg bw/day (actual dose received)
Dose / conc.:: 1 000 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:: Total: 72
0 mg/kg bw: 6 male, 6 female
250 mg/kg bw: 6 male, 6 female
500 mg/kg bw: 6 male, 6 female
1000 mg/kg bw: 6 male, 6 female

Reversal group
0 mg/kg bw: 6 male, 6 female
1000 mg/kg bw: 6 male, 6 female
Control animals:: yes, concurrent vehicle
Details on study design:: - Dose selection rationale:
- Rationale for animal assignment (if not random):The animals of uniform body weight were selected. The individual body weights of the animals did not exceed ± 20% of group mean body weight. The group means body weights of all the groups were approximately equal.
- Other:
Positive control:: No Data Available
Observations and examinations performed and frequency:: CAGE SIDE OBSERVATIONS: Yes
- Time schedule:twice daily
- Cage side observations checked in table [No.?] were included. Viability were observed

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:daily

BODY WEIGHT: Yes
- Time schedule for examinations:Body weights were recorded on the day of randomization, day of first dosing, weekly thereafter and a fasting body weight at scheduled sacrifice on day 29 and day 43.

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: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes

FOOD EFFICIENCY:Not specified
- 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: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified
- Time schedule for examinations:Not specified

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: prior to the initiation of the dosing and at scheduled sacrifice.
- Dose groups that were examined: All dose group were examined.

HAEMATOLOGY: Yes
- Time schedule for collection of blood:At the end of dosing period on day 29 and at termination of recovery period on day 43.
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Yes, overnight
- How many animals: All 72 animals were examined.
- Parameters checked in table [No.?] were examined.Hemoglobin (g/dL), Red Blood Corpuscles (x 106 /µL), Hematocrit (%), Mean Corpuscular Volume (fL), Mean Corpuscular Hemoglobin (pg), Mean Corpuscular Hemoglobin Concentration (g/dL), Platelets (x 103 /µL), White Blood Corpuscles (x 103 /µL), Reticulocytes (%), Neutrophils (%), Lymphocytes (%), Eosinophils (%), Monocytes (%), Basophil (%) and Prothrombin time (sec.) were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood:At the end of dosing period on day 29 and at termination of recovery period on day 43.
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Yes, overnight
- How many animals: All 72 animals were examined.
- Parameters checked in table [No.?] were examined.: Total Protein (g/dL), Blood Urea Nitrogen (mg/dL), Urea Nitrogen (mg/dL) Calculated, Alanine Aminotransferase (U/L), Aspartate Aminotransferase (U/L), Alkaline Phosphatase (U/L), Gamma Glutamyl Transferase (U/L), Glucose (mg/dL), Calcium (mmol/L), Phosphorous (mg/dL), Albumin (g/dL), Total Bilirubin (mg/dL), Creatinine (mmol/L), Total Cholesterol (mg/dL), Triglycerides (mg/dL), Globulin (g/dL) Calculated, Sodium (mmol/L), Potassium (mmol/L), Chloride (mmol/L) and Bile acid (mmol/L) were examined.

URINALYSIS: Yes
- Time schedule for collection of urine: during the last week of dosing period and on reversal group rats at termination of recovery period on day 43.
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Not specified
- Parameters checked in table [No.?] were examined.: Volume, Appearance, Colour, pH, Specific Gravity, Proteins, Glucose, Ketones, Bilirubin, Urobililogen, Occult Blood and Nitrite were examined.

NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Towards the end of the exposure period of 28 days and towards the end of the recovery period on day 42
- Dose groups that were examined:All dose group were examined.
- Battery of functions tested: sensory activity, grip strength, motor activity, Visual Placing Response were examined.

IMMUNOLOGY: Not specified
- Time schedule for examinations:Not specified
- How many animals:Not specified
- Dose groups that were examined:Not specified
- Parameters checked in table [No.?] were examined.Not specified

OTHER:Organ Weights were examined.
Sacrifice and pathology:: GROSS PATHOLOGY: Yes
after 28 consecutive days of oral administration, all surviving study rats were sacrificed on day 29 (Group I, III, IV, V). In addition all rats from reversal groups were sacrificed on day 43 (Group II and VI).

HISTOPATHOLOGY: Yes
From each rat, samples or the whole of the tissues listed below were preserved. All tissues were fixed in 10% neutral buffered formalin except, eyes and testes of all animals were preserved in Davidson’s solution for 24 hours and transferred to 10% neutral buffered formalin.
Other examinations:: No Data Available
Statistics:: Raw data was processed and analyzed for reporting group means and standard deviations with significance between the controls and treated groups, using SYSTAT 13 validated statistical software supplied by Starcom Information Technology Limited, Bangalore developed by Systat Software, Inc. USA. All the parameters characterized by continuous data such as body weight, feed consumption (calculated as gram per animal), organ weight, relative organ weight, haematological and clinical chemistry data were subjected to Bartlett’s test to meet the homogeneity of variance before conducting Analysis of Variance (ANOVA) and Dunnett’s t-test. Where the data was not meet the homogeneity of variance, Student’s t-test were performed to calculate significance.

Significance was calculated at 5% level and indicated in the summary tables as follows:

* = Significant than control at 95% level of confidence (p<0.05).
Clinical signs:: no effects observed
Description (incidence and severity):: Male -
Group I (Control, 0 mg/kg): No clinical signs of toxicity were observed in the animals throughout the dosing period of 28 days (animal nos.1 to 6).
Group II (Control, 0 mg/kg, Reversal): No clinical signs of toxicity were observed in the animals throughout the dosing period of 28 days and during the post-dosing recovery period (animal nos.13 to 18).
Group III (250 mg/kg): No clinical signs of toxicity were observed in the animals throughout the dosing period of 28 days (animal nos.25 to 30).
Group IV (500 mg/kg): No clinical signs of toxicity were observed in the animals throughout the dosing period of 28 days (animal nos.37 to 42).
Group V (1000 mg/kg): No clinical signs of toxicity were observed in the animals throughout the dosing period of 28 days (animal nos.49 to 54).
Group VI (1000 mg/kg, Reversal): No clinical signs of toxicity were observed in the animals throughout the dosing period of 28 days and during the post-dosing recovery period (animal nos.61 to 66).

Female -
Group I (Control, 0 mg/kg): No clinical signs of toxicity were observed in the animals throughout the dosing period of 28 days (animal nos.7 to 12).
Group II (Control, 0 mg/kg, Reversal): No clinical signs of toxicity were observed in the animals throughout the dosing period of 28 days and during the post-dosing recovery period (animal nos.19 to 24).
Group III (250 mg/kg): No clinical signs of toxicity were observed in the animals throughout the dosing period of 28 days (animal nos.31 to 36).
Group IV (500 mg/kg): No clinical signs of toxicity were observed in the animals throughout the dosing period of 28 days (animal nos.43 to 48).
Group V (1000 mg/kg): No clinical signs of toxicity were observed in the animals throughout the dosing period of 28 days (animal nos.55 to 60).
Group VI (1000 mg/kg, Reversal): No clinical signs of toxicity were observed in the animals throughout the dosing period of 28 days and during the post-dosing recovery period (animal nos.67 to 72).
Mortality:: no mortality observed
Description (incidence):: Male and Female -
All animals from control and different dose groups survived throughout the dosing period of 28 days and the post-dosing recovery period of 14 days.
Body weight and weight changes:: no effects observed
Description (incidence and severity):: Male and Female -
Animals from control and different dose groups exhibited normal body weight gain throughout the dosing period of 28 days.
During the post-dosing recovery period, animals from 1000 mg/kg reversal group exhibited normal body weight gain when compared with that of control animals.
Food consumption and compound intake (if feeding study):: no effects observed
Description (incidence and severity):: Male and Female -
Animals from control and different dose groups exhibited normal feed consumption at the end of the dosing period of 28 days.
Animals from control reversal and high reversal dose groups exhibited normal feed consumption at the end of the recovery period of 14 days.
Food efficiency:: not specified
Water consumption and compound intake (if drinking water study):: not specified
Ophthalmological findings:: no effects observed
Description (incidence and severity):: No ocular abnormalities were observed on ophthalmological examination in the animals during pre-exposure and at the end of the respective termination.
Haematological findings:: no effects observed
Description (incidence and severity):: Male and Female -
Haematological investigations conducted at the end of dosing period on day 29 and at the end of recovery period on day 43, revealed no significant changes in the values of different parameters studied when compared with that of respective controls.
Clinical biochemistry findings:: no effects observed
Description (incidence and severity):: Male and Female -
Biochemical investigations conducted at the end of dosing period on day 29 and at the end of recovery period on day 43, revealed following significant changes in the values of different parameters studied when compared with that of respective controls, however the increase/decreased in the values obtained was within normal biological and laboratory limits or the effect was not dose dependent.
Male :
Chloride : Elevated levels were observed in animals from 500 mg/kg dose group, sacrificed on day 29 (p<0.05),
Total Protein : Decreased levels were observed in animals from 500 mg/kg and 1000 mg/kg dose groups, sacrificed on day 29 (p<0.05),
Calcium : Decreased levels were observed in animals from 250 mg/kg and 500 mg/kg dose groups, sacrificed on day 29 (p<0.05),
Globulin and Sodium : Decreased levels were observed in animals from 500 mg/kg dose group, sacrificed on day 29 (p<0.05) and
Creatinine : Decreased levels were observed in animals from 1000 mg/kg reversal dose group, sacrificed on day 43 (p<0.05).

Female :
Blood Urea Nitrogen and Urea Nitrogen : Elevated levels were observed in animals from 250 mg/kg dose group, sacrificed on day 29 (p<0.05),
Phosphorous : Elevated levels were observed in animals from 250 mg/kg and 1000 mg/kg dose groups, sacrificed on day 29 (p<0.05),
Gamma Glutamyl Transferase and Creatinine : Elevated levels were observed in animals from 250 mg/kg and 500 mg/kg dose groups, sacrificed on day 29 (p<0.05),
Total Protein, Total Bilirubin, Albumin and Globulin: Decreased levels were observed in animals from 500 mg/kg dose group, sacrificed on day 29 (p<0.05),
Alanine Aminotransferase and Alkaline Phosphatase : Decreased levels were observed in animals from 250 mg/kg and 500 mg/kg dose groups, sacrificed on day 29 (p<0.05) and
Alanine Aminotransferase and Calcium : Decreased levels were observed in animals from 1000 mg/kg reversal dose group, sacrificed on day 43 (p<0.05).
Urinalysis findings:: no effects observed
Description (incidence and severity):: Male and Female -
No statistically significant variation was observed in the urine analyses conducted at the end of the dosing period in week 4 and 6 (on day 23, 24, 25 and 43) in male and female animals from different dose groups as compared to control group animals, except for lower volume of urine was observed in female animals from 1000 mg/kg reversal dose group (p<0.05). This lower volume of urine analyses were considered to be incidental and of no toxicological importance.
Behaviour (functional findings):: no effects observed
Description (incidence and severity):: Sensory Reactivity Observations:
All animals from control and different dose groups showed normal arousal level, visual response, touch response, auditory response, tail pinch response and visual placing response. Normal air righting reflex was observed in all animals from control and different dose groups in week 4.

Grip Strength:
Grip strength values observed in male and female animals for control and different dose groups were comparable.

Motor Activity:
Motor activity values observed in male and female animals for control and different dose groups were comparable.
Immunological findings:: not specified
Organ weight findings including organ / body weight ratios:: no effects observed
Description (incidence and severity):: Male -
In comparison with controls at the end of dosing on day 29, male animals from 1000 mg/kg dose group revealed decreased relative weights of kidneys and adrenals (p<0.05).
In comparison with controls at the end of post-dosing recovery period on day 43, organ weight data of animals from 1000 mg/kg reversal group revealed increased relative weights of liver, kidneys and spleen (p<0.05).
Female -
In comparison with controls at the end of dosing on day 29, organ weight data of animals from 250 mg/kg dose group revealed increased relative weights of kidneys (p<0.05).
In comparison with controls at the end of post-dosing recovery period on day 43, organ weight data of animals from 1000 mg/kg reversal group revealed increased relative weights of liver, kidneys, heart and spleen (p<0.05).

Although significant changes in the values of organ weight were observed in male and female animals from different dose groups, no related gross pathological and histopathological findings were seen, hence these findings were considered to be of no toxicological importance.
Gross pathological findings:: no effects observed
Description (incidence and severity):: Gross pathological examination on male and female animals from control and different dose groups did not reveal any abnormality.
Neuropathological findings:: not specified
Histopathological findings: non-neoplastic:: no effects observed
Description (incidence and severity):: No treatment related histopathological changes were evident in male and female animals from control and high dose groups.
Incidental and physiological histopathological changes which were covered in the background historical data of the pathology from control and high dose groups includes minimal, focal to multifocal periportal mononuclear cells infiltration in liver; minimal multifocal, tubular eosinophilic secretion and/or tubular dilatation in the kidneys; minimal multifocal brown pigmentation in spleen; minimal, diffuse dilatation of zona reticularis and/or minimal multifocal vacuolation in zona fasciculata in the adrenals; minimal, luminal seminal coagulum in urinary bladder; minimal, diffuse luminal dilatation in the uterus; presence of ultimobranchial cyst in the thyroid in male and female animals from control and high dose group.
Histopathological findings: neoplastic:: not specified
Other effects:: not specified
Dose descriptor:: NOAEL
Effect level:: 1 000 mg/kg bw/day (actual dose received)
Based on:: test mat.
Sex:: male/female
Basis for effect level:: behaviour (functional findings); body weight and weight gain; clinical biochemistry; clinical signs; food consumption and compound intake; gross pathology; haematology; histopathology: non-neoplastic; mortality; ophthalmological examination; organ weights and organ / body weight ratios; urinalysis
Remarks on result:: other: No effect obseved
Critical effects observed:: not specified
System:: other: not specified
Organ:: not specified
Conclusions:: The No Observed Adverse Effect Level (NOAEL) for repeated dose toxicity was considered to be 1000 mg/kg/day, when male and female Sprague Dawley rats were administered the test chemical via oral route during 28 consecutive days and 14-day recovery period.
Executive summary:: A repeated dose 28-day oral toxicity studywas performed to determine the toxic profile ofthe test chemical when administered daily for 28 consecutive days for Sprague-Dawley rats. The test substance was administered to rats at dose levels of0 (vehicle control), 250, 500 and 1000 mg/kg body weight/day. Two additional doseswere added to the study as control (0 mg/kg/day) and 1000 mg/kg/day in order to study delayed toxiceffects orreversibilityy. The control animals were administered with corn oil. All treated animals were survived through the dosing period of 28-day and the recovery period of 14-days. No sign of toxicity was noted throughout the dosing and recovery periods. Treated rats exhibited normal body weight gain and the food consumption, which were comparable with controls. Detailed clinical observation conducted weekly did not reveal any abnormalities at any dose during the dosing and recovery periods. Ophthalmoscopic examination, conducted prior to and after the dosing period did not reveal any abnormalities.At the end of administration period, in week 4^thfunctional observation battery was performed to assess sensory reactivity to diverse stimulus, grip strength and motor activity. This functional observational battery did not reveal any differences between treated and control rats.Haematological analysis was carried out on termination days (day 29 and 43) and it did not reveal any abnormalities. In clinical biochemistry the total protein level, which reflectsthetotal amount of albumin and globulin, was significantly decreased at 500 and 1000 mg/kg/day in males and at 500 mg/kg/day in females. Creatinine concentration dropped significantly at the top dose in males, but no similar changes were seen in females. In females the alanine transaminase (ALT) and alkaline phosphatase (ALP) levels, which are indicators of liver function dropped significantly at 250, and 500 mg/kg/day, and theALTlevelin serumremained reduced at day 43. However, no similar effects on serum liver enzymes concentration was seen in male rats. In summary, no conclusive and dose-dependent alteration of serum parameters were revealed, the observed increase/decrease in concentrations were marginal and within the normal laboratory and biological limits.At the end of dosing period of 28-day, the relative weight of kidney and adrenals decreased significantly at 1000 mg/kg/day as compared to control, but no similar effect was noted among females. At the termination of recovery period (at day 43) the relative weight of liver, kidney and spleen increased significantly in both males and females. Although significant changes in organ weight were observed in male and female rats in different dose group, no related gross pathological and histopathological finding were seen and therefore, these finding were considered to be of no toxicological importance. Gross pathological and histopathological observation of organs did not reveal abnormalities at any dose level in both sexes. In conclusion, the repeated oral exposure tothe test chemicaldid notinduced toxicologically significant and severe alterations of the function or morphology of a specific tissue/organ, neither produced serious changes to the biochemistry or haematology of animalswhen SD rats were orally administered for 28 consecutive days followed by a 14-day recovery period.

Endpoint conclusion

Endpoint conclusion:: no adverse effect observed
Dose descriptor:: NOAEL
: 1 000 mg/kg bw/day
Study duration:: subacute
Species:: rat
Quality of whole database:: The data is from a study report is considered as Klimisch 1.
System:: other: Not Specified

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:: repeated dose toxicity: inhalation, other
Data waiving:: other justification
Justification for data waiving:: a sub-chronic toxicity study (90 days) does not need to be conducted because the substance is unreactive, insoluble and not inhalable and there is no evidence of absorption and no evidence of toxicity in a 28-day 'limit test' and human exposure is limited

Endpoint conclusion

Endpoint conclusion:: no study available

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:: repeated dose toxicity: inhalation, other
Data waiving:: other justification
Justification for data waiving:: a sub-chronic toxicity study (90 days) does not need to be conducted because the substance is unreactive, insoluble and not inhalable and there is no evidence of absorption and no evidence of toxicity in a 28-day 'limit test' and human exposure is limited

Endpoint conclusion

Endpoint conclusion:: no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:: repeated dose toxicity: dermal, other
Data waiving:: other justification
Justification for data waiving:: a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:: no study available

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:: repeated dose toxicity: dermal, other
Data waiving:: other justification
Justification for data waiving:: a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:: no study available

Additional information

Data available for the test chemical were reviewed to determine the toxic nature of oxacycloheptadec-10-en-2-one (CAS 28645-51-4) following repeated exposure via oral route. The study is summarized below:

Repeated dose toxicity via oral route:

A repeated dose 28-day oral toxicity study was performed to determine the toxic profile ofthe test chemical when administered daily for 28 consecutive days for Sprague-Dawley rats. The test substance was administered to rats at dose levels of0 (vehicle control), 250, 500 and 1000 mg/kg body weight/day. Two additional doseswere added to the study as control (0 mg/kg/day) and 1000 mg/kg/day in order to study delayed toxiceffects orreversibility. The control animals were administered with corn oil. All treated animals were survived through the dosing period of 28-day and the recovery period of 14-days. No sign of toxicity was noted throughout the dosing and recovery periods. Treated rats exhibited normal body weight gain and the food consumption, which were comparable with controls. Detailed clinical observation conducted weekly did not reveal any abnormalities at any dose during the dosing and recovery periods. Ophthalmoscopic examination, conducted prior to and after the dosing period did not reveal any abnormalities.At the end of administration period, in week 4^thfunctional observation battery was performed to assess sensory reactivity to diverse stimulus, grip strength and motor activity. This functional observational battery did not reveal any differences between treated and control rats.Haematological analysis was carried out on termination days (day 29 and 43) and it did not reveal any abnormalities. In clinical biochemistry the total protein level, which reflectsthetotal amount of albumin and globulin, was significantly decreased at 500 and 1000 mg/kg/day in males and at 500 mg/kg/day in females. Creatinine concentration dropped significantly at the top dose in males, but no similar changes were seen in females. In females the alanine transaminase (ALT) and alkaline phosphatase (ALP) levels, which are indicators of liver function dropped significantly at 250, and 500 mg/kg/day, and theALTlevelin serumremained reduced at day 43. However, no similar effects on serum liver enzymes concentration was seen in male rats. In summary, no conclusive and dose-dependent alteration of serum parameters were revealed, the observed increase/decrease in concentrations were marginal and within the normal laboratory and biological limits.At the end of dosing period of 28-day, the relative weight of kidney and adrenals decreased significantly at 1000 mg/kg/day as compared to control, but no similar effect was noted among females. At the termination of recovery period (at day 43) the relative weight of liver, kidney and spleen increased significantly in both males and females. Although significant changes in organ weight were observed in male and female rats in different dose group, no related gross pathological and histopathological finding were seen and therefore, these finding were considered to be of no toxicological importance. Gross pathological and histopathological observation of organs did not reveal abnormalities at any dose level in both sexes. In conclusion, the repeated oral exposure tothe test chemicaldid notinduced toxicologically significant and severe alterations of the function or morphology of a specific tissue/organ, neither produced serious changes to the biochemistry or haematology of animalswhen SD rats were orally administered for 28 consecutive days followed by a 14-day recovery period.

Repeated dose toxicity via inhalation route:

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 oxacycloheptadec-10-en-2-one (28645-51-4) which is reported as 2.2351839 10^-5Hgmm at 25°C. Thus, exposure to inhalable dust, mist and vapour of the chemical oxacycloheptadec-10-en-2-oneis highly unlikely and, therefore this endpoint is considered for waiver.

Repeated dose toxicity via dermal route:

The acute toxicity value for oxacycloheptadec-10-en-2-one (28645-51-4) (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that oxacycloheptadec-10-en-2-one shall not exhibit toxic effects via dermal after 28-day exposure. In addition, there is no data available that suggests that oxacycloheptadec-10-en-2-one shall exhibit repeated dose toxicity via dermal route and therefore this endpoint was considered for waiver.

Justification for classification or non-classification

Based on the data available for the test chemical, oxacycloheptadec-10-en-2-one( CAS 28645-51-4) does not exhibit toxic effects upon repeated exposure by oral, inhalation and dermal routes of exposure and, consequently it is not classified for specific target organ toxicity following repeated exposure (STOT-RE) according to the criteria of the CLP regulations.

Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

	Dose (mg/kg)		Mortality
Group	Dose (mg/kg)		Males		Females
Number	Male	Female	Absolute	Relative %	Absolute	Relative %
I	0	0	0/6	0	0/6	0
II	0 (Reversal)	0 (Reversal)	0/6	0	0/6	0
III	250	250	0/6	0	0/6	0
IV	500	500	0/6	0	0/6	0
V	1000	1000	0/6	0	0/6	0
VI	1000 (Reversal)	1000 (Reversal)	0/6	0	0/6	0

Group	Dose (mg/kg)		Weeks
Number	Dose (mg/kg)		Day 0	Day 1	1	2	3
I	0	Mean	164.87	168.03	194.95	230.83	264.98
I	0	±SD	13.20	12.77	10.59	12.86	11.42
II	0 (Reversal)	Mean	164.55	168.12	194.03	231.60	262.95
II	0 (Reversal)	±SD	11.92	11.73	11.49	12.40	13.08
III	250	Mean	164.92	169.08	194.22	222.38	254.47
III	250	±SD	11.32	11.36	13.67	13.35	15.06
IV	500	Mean	165.77	168.57	192.88	221.22	256.47
IV	500	±SD	10.63	9.99	10.17	13.21	17.66
V	1000	Mean	165.65	169.72	194.37	221.37	256.65
V	1000	±SD	9.80	8.79	11.03	10.85	12.72
VI	1000 (Reversal)	Mean	167.45	170.62	192.02	221.33	255.67
VI	1000 (Reversal)	±SD	7.44	7.49	9.00	11.35	10.74

Group	Dose (mg/kg)		Weeks
Number	Dose (mg/kg)		4	5	6
I	0	Mean	297.30
I	0	±SD	11.13
II	0 (Reversal)	Mean	292.52	319.82	336.18
II	0 (Reversal)	±SD	13.34	11.31	10.40
III	250	Mean	286.77
III	250	±SD	16.40
IV	500	Mean	283.43
IV	500	±SD	17.21
V	1000	Mean	285.87
V	1000	±SD	11.25
VI	1000 (Reversal)	Mean	282.92	307.52	323.65
VI	1000 (Reversal)	±SD	10.81	11.05	10.61

Group	Dose (mg/kg)		Weeks
Number	Dose (mg/kg)		Day 0	Day 1	1	2	3
I	0	Mean	149.85	151.63	170.60	188.38	205.15
I	0	±SD	11.03	11.19	12.30	13.69	11.81
II	0 (Reversal)	Mean	150.45	152.12	172.77	190.17	206.58
II	0 (Reversal)	±SD	9.97	10.04	11.28	12.22	12.03
III	250	Mean	150.18	151.57	168.28	185.82	204.52
III	250	±SD	10.54	10.56	11.73	14.16	14.09
IV	500	Mean	151.03	152.73	167.93	185.08	202.17
IV	500	±SD	8.64	8.63	10.17	10.10	8.33
V	1000	Mean	151.47	152.85	168.47	185.93	204.90
V	1000	±SD	8.95	8.92	9.45	9.39	8.15
VI	1000 (Reversal)	Mean	150.83	152.42	166.12	180.37	195.03
VI	1000 (Reversal)	±SD	6.59	6.60	8.39	11.51	9.17

Group	Dose (mg/kg)		Weeks
Number	Dose (mg/kg)		4	5	6
I	0	Mean	228.38
I	0	±SD	12.47
II	0 (Reversal)	Mean	226.98	248.13	259.83
II	0 (Reversal)	±SD	11.97	12.18	11.33
III	250	Mean	222.45
III	250	±SD	12.54
IV	500	Mean	224.32
IV	500	±SD	7.97
V	1000	Mean	223.22
V	1000	±SD	9.44
VI	1000 (Reversal)	Mean	218.45	237.47	251.63
VI	1000 (Reversal)	±SD	8.65	10.43	11.77

Group Number	Dose mg/kg	Ophthalmoscopic Finding	Total Number of Animals	Animal Number
I	0	No abnormality detected	6	1 - 6
II	0 (Rev.)	No abnormality detected	6	13 - 18
III	250	No abnormality detected	6	25 - 30
IV	500	No abnormality detected	6	37 - 42
V	1000	No abnormality detected	6	49 - 54
VI	1000 (Rev.)	No abnormality detected	6	61 - 66

Group Number		I	II	III	IV	V	VI
Dose		0 mg/kg	0 mg/kg Reversal	250 mg/kg	500 mg/kg	1000 mg/kg	1000 mg/kg Reversal
Number of animals observed		6	6	6	6	6	6
Number of animals within normal limit		6/6	6/6	6/6	6/6	6/6	6/6
Number of animals with significant deviation		0/6	0/6	0/6	0/6	0/6	0/6
Parameters
Arousal level : Apparently normal		6/6	6/6	6/6	6/6	6/6	6/6
Visual response : Orienting response		6/6	6/6	6/6	6/6	6/6	6/6
Touch response : Orienting response		6/6	6/6	6/6	6/6	6/6	6/6
Auditory response : Orienting response		6/6	6/6	6/6	6/6	6/6	6/6
Tail pinch response : Orienting response		6/6	6/6	6/6	6/6	6/6	6/6
Visual placing response : Early extension of forelimbs to reach for the screen		6/6	6/6	6/6	6/6	6/6	6/6
Air righting response : Lands with all feet on ground		6/6	6/6	6/6	6/6	6/6	6/6
Grip Strength (kg) - Mean ± SD		0.916 ±0.022	0.911 ±0.049	0.924 ±0.050	0.913 ±0.023	0.903 ±0.029	0.908 ±0.052
Motor Activity -	Interval ‘1’	523.67 ±143.69	540.00 ±89.14	524.67 ±91.60	518.67 ±77.65	528.17 ±84.63	518.50 ±110.10
Mean ± SD	Interval ‘2’	251.83 ±89.56	440.50 ±152.68	256.50 ±118.31	297.00 ±127.20	280.83 ±137.95	408.50 ±65.63
	Interval ‘3’	145.17 ±80.16	315.17 ±133.54	166.17 ±164.59	158.83 ±49.88	167.50 ±138.95	321.17 ±67.93

Group	Dose (mg/kg)		Hb	Total RBC	Rt	HCT	MCV	MCH	MCHC
Number	Dose (mg/kg)		(g/dL)	(⁶/µL)	(%)	(%)	(fL)	(pg)	(g/dL)
I	0	Mean	15.20	8.08	4.25	47.35	58.62	18.85	32.12
I	0	±SD	2.11	1.12	0.50	6.57	1.08	0.34	0.28
II	0 (Reversal)	Mean	15.13	8.12	4.25	45.78	56.32	18.62	33.02
II	0 (Reversal)	±SD	1.34	0.58	0.82	4.16	1.30	0.40	0.15
III	250	Mean	16.13	8.50	4.37	49.23	57.90	18.97	32.80
III	250	±SD	0.77	0.36	0.78	2.42	1.42	0.35	0.30
IV	500	Mean	16.73	8.80	4.43	51.43	58.45	19.03	32.53
IV	500	±SD	1.16	0.49	0.62	3.20	1.25	0.50	0.34
V	1000	Mean	16.23	8.54	4.62	50.52	59.27	19.10	32.18
V	1000	±SD	0.60	0.58	0.49	2.42	2.68	0.96	0.79
VI	1000 (Reversal)	Mean	14.67	8.00	4.67	45.02	56.27	18.32	32.62
VI	1000 (Reversal)	±SD	1.28	0.58	0.99	3.63	1.19	0.57	0.55

Group	Dose (mg/kg)		Platelets	Total WBC	Differential %					Pt.
Number	Dose (mg/kg)		(³/ µL)	(³/µL)	N	L	E	M	B	(Sec.)
I	0	Mean	363.00	12.98	18.33	80.33	0.67	0.67	0.00	19.67
I	0	±SD	82.51	3.68	3.27	3.88	0.82	0.82	0.00	4.97
II	0 (Reversal)	Mean	332.33	11.52	15.50	83.00	0.83	0.67	0.00	20.17
II	0 (Reversal)	±SD	146.47	4.67	2.43	2.10	0.75	0.82	0.00	3.71
III	250	Mean	390.17	12.82	19.33	79.50	0.83	0.33	0.00	17.83
III	250	±SD	20.87	2.26	2.94	2.95	0.75	0.52	0.00	7.60
IV	500	Mean	386.83	13.35	18.00	80.00	1.17	0.83	0.00	19.67
IV	500	±SD	90.09	2.96	3.03	2.97	0.75	0.75	0.00	7.42
V	1000	Mean	420.33	13.65	18.33	80.67	0.33	0.67	0.00	17.50
V	1000	±SD	35.27	2.64	2.94	3.20	0.52	0.82	0.00	4.51
VI	1000 (Reversal)	Mean	314.83	11.78	16.50	82.33	0.50	0.67	0.00	21.17
VI	1000 (Reversal)	±SD	73.89	3.47	2.26	2.07	0.55	0.82	0.00	4.45

Group Number	Dose (mg/kg)	Animal Nos.	Cell Morphology
I	0	1 - 6	Normocytic, Normochromic
II	0 (Reversal)	13 - 18	Normocytic, Normochromic
III	250	25 - 30	Normocytic, Normochromic
IV	500	37 - 42	Normocytic, Normochromic
V	1000	49 - 54	Normocytic, Normochromic
VI	1000 (Reversal)	61 - 66	Normocytic, Normochromic

Group Number	Dose (mg/kg)		TotalProtein (g/dL)	BUN (mg/dL)	Urea Nitrogen (mg/dL)	ALT (U/L)	AST (U/L)	ALP (U/L)	Glucose (mg/dL)
I	0	Mean	7.01	19.00	41.42	56.00	100.17	139.33	103.00
I	0	±SD	0.25	1.55	3.38	11.82	7.96	43.44	5.62
II	0 (Reversal)	Mean	6.25	18.00	39.24	44.67	96.17	79.33	87.83
II	0 (Reversal)	±SD	0.11	1.90	4.14	9.16	14.80	16.12	2.32
III	250	Mean	6.85	15.83	34.52	61.67	100.17	176.00	102.50
III	250	±SD	0.11	2.56	5.59	11.29	15.66	57.86	46.48
IV	500	Mean	6.54*	18.33	39.97	67.00	86.33	185.33	94.33
IV	500	±SD	0.20	1.37	2.98	3.52	10.41	24.21	12.56
V	1000	Mean	6.72*	17.83	38.88	61.50	96.17	171.50	102.83
V	1000	±SD	0.14	1.94	4.23	9.03	11.20	58.87	9.83
VI	1000 (Reversal)	Mean	6.49	16.50	35.97	49.33	100.67	76.33	86.50
VI	1000 (Reversal)	±SD	0.27	2.07	4.52	4.97	6.71	23.11	5.54

Group Number	Dose (mg/kg)		Calcium(mmol/L)	Phospho-rous (mg/dL)	GGT (U/L)	Total Bilirubin (mg/dL)	Albumin (g/dL)	Globulin (g/dL)	Creatinine (mg/dL)
I	0	Mean	3.83	7.88	5.33	0.10	1.17	5.83	0.43
I	0	±SD	0.07	0.56	0.52	0.03	0.09	0.20	0.08
II	0 (Reversal)	Mean	3.88	7.73	5.00	0.18	1.58	4.67	0.48
II	0 (Reversal)	±SD	0.10	0.63	1.41	0.02	0.17	0.19	0.04
III	250	Mean	3.60*	7.92	5.33	0.13	1.10	5.75	0.41
III	250	±SD	0.13	1.23	0.52	0.01	0.16	0.25	0.03
IV	500	Mean	3.59*	8.85	4.83	0.13	1.12	5.40*	0.44
IV	500	±SD	0.09	0.82	0.75	0.01	0.08	0.18	0.05
V	1000	Mean	3.73	7.97	5.33	0.11	1.15	5.58	0.47
V	1000	±SD	0.16	0.42	1.03	0.04	0.10	0.10	0.05
VI	1000 (Reversal)	Mean	3.82	8.55	5.33	0.18	1.58	4.90	0.40*
VI	1000 (Reversal)	±SD	0.10	0.78	0.52	0.01	0.09	0.27	0.02

Group Number	Dose (mg/kg)		Sodium (mmol/L)	Potassium (mmol/L)	Chloride (mmol/L)	Total Cholesterol (mg/dL)	Triglycerides (mg/dL)	Bile Acids (µmol/L)
I	0	Mean	148.45	4.42	106.29	48.83	49.00	29.65
I	0	±SD	1.86	0.62	1.14	5.78	16.58	23.10
II	0 (Reversal)	Mean	146.90	4.25	106.91	44.33	62.33	9.90
II	0 (Reversal)	±SD	1.23	0.40	0.98	8.41	18.02	7.13
III	250	Mean	146.89	4.00	107.12	47.67	61.67	24.58
III	250	±SD	0.71	0.28	0.83	8.12	20.05	20.37
IV	500	Mean	145.94*	4.05	108.92*	44.50	57.33	10.76
IV	500	±SD	1.86	0.26	1.75	10.21	18.50	3.85
V	1000	Mean	146.36	4.20	108.20	47.00	59.83	18.07
V	1000	±SD	1.02	0.69	1.76	6.87	16.80	6.58
VI	1000 (Reversal)	Mean	146.55	4.52	106.68	49.50	84.33	7.89
VI	1000 (Reversal)	±SD	1.32	0.57	1.23	14.86	39.27	4.05

Group	Dose		Volume	Glucose	Bilirubin	Ketones	Sp.Gr.	Occult Blood
Number	mg TOS/kg		(ml)	(mmol/L)	(mmol/L)	(mmol/L)	(g/L)	(caCELLS/µL)
I	0	Mean	6.383	-ve	-ve	-ve	1.017	-ve
I	0	±SD	0.911	-ve	-ve	-ve	0.003	-ve
II	0 (Rev.)	Mean	6.267	-ve	-ve	-ve	1.018	-ve
II	0 (Rev.)	±SD	0.565	-ve	-ve	-ve	0.003	-ve
III	250	Mean	6.233	-ve	-ve	-ve	1.017	-ve
III	250	±SD	0.539	-ve	-ve	-ve	0.003	-ve
IV	500	Mean	5.567	-ve	-ve	-ve	1.018	-ve
IV	500	±SD	0.859	-ve	-ve	-ve	0.003	-ve
V	1000	Mean	6.983	-ve	-ve	-ve	1.017	-ve
V	1000	±SD	0.471	-ve	-ve	-ve	0.003	-ve
VI	1000 (Rev.)	Mean	6.233	-ve	-ve	-ve	1.018	-ve
VI	1000 (Rev.)	±SD	1.178	-ve	-ve	-ve	0.003	-ve

Group	Dose		pH	Urobilinogen	Nitrite
Number	mg TOS/kg			(mmol/L)
I	0	Mean	7.250	-ve	-ve
I	0	±SD	0.274	-ve	-ve
II	0 (Rev.)	Mean	7.250	-ve	-ve
II	0 (Rev.)	±SD	0.274	-ve	-ve
III	250	Mean	7.167	-ve	-ve
III	250	±SD	0.258	-ve	-ve
IV	500	Mean	7.250	-ve	-ve
IV	500	±SD	0.274	-ve	-ve
V	1000	Mean	7.083	-ve	-ve
V	1000	±SD	0.204	-ve	-ve
VI	1000 (Rev.)	Mean	7.250	-ve	-ve
VI	1000 (Rev.)	±SD	0.274	-ve	-ve

Group	Dose (mg/kg)		Day
Number	Dose (mg/kg)		1	8	15	22	28
I	0	Mean	18.80	20.33	23.52	23.75	24.77
II	0 (Reversal)	Mean	18.55	20.25	21.55	24.18	25.02
III	250	Mean	18.58	19.52	21.25	23.55	24.92
IV	500	Mean	18.48	19.95	21.53	23.93	25.38
V	1000	Mean	18.42	19.63	21.37	23.33	25.02
VI	1000 (Reversal)	Mean	18.48	19.78	20.85	23.32	24.48

Group	Dose (mg/kg)		Day
Number	Dose (mg/kg)		1	8	15	22	28
I	0	Mean	14.67	16.80	18.03	19.23	20.43
II	0 (Reversal)	Mean	14.98	16.77	18.13	19.33	19.93
III	250	Mean	14.28	16.20	17.52	18.80	20.13
IV	500	Mean	14.38	15.63	17.43	18.63	19.85
V	1000	Mean	14.13	16.32	17.58	18.75	19.58
VI	1000 (Reversal)	Mean	14.27	15.75	16.80	18.10	19.63

Group Number	Dose (mg/kg)		TotalProtein (g/dL)	BUN (mg/dL)	Urea Nitrogen (mg/dL)	ALT (U/L)	AST (U/L)	ALP (U/L)	Glucose (mg/dL)
I	0	Mean	6.96	16.83	36.70	51.50	100.00	119.83	94.17
I	0	±SD	0.43	1.83	4.00	7.77	21.73	24.65	10.19
II	0 (Reversal)	Mean	7.13	16.67	36.33	60.17	112.50	112.17	91.50
II	0 (Reversal)	±SD	0.22	3.14	6.85	18.13	15.63	40.35	12.37
III	250	Mean	6.77	19.67*	42.87*	36.00*	132.00	70.50*	92.67
III	250	±SD	0.31	1.75	3.82	10.64	20.23	15.77	4.93
IV	500	Mean	6.22*	19.50	42.51	38.50*	116.50	64.00*	94.00
IV	500	±SD	0.55	2.26	4.92	6.89	22.63	14.67	11.68
V	1000	Mean	6.86	17.33	37.79	54.67	98.67	143.83	96.00
V	1000	±SD	0.24	1.21	2.64	6.65	21.09	32.54	8.00
VI	1000 (Reversal)	Mean	6.68	17.17	37.42	41.00*	105.50	70.83	90.83
VI	1000 (Reversal)	±SD	0.60	3.82	8.32	7.95	17.93	22.23	6.59

Group Number	Dose (mg/kg)		Sodium (mmol/L)	Potassium (mmol/L)	Chloride (mmol/L)	Total Cholesterol (mg/dL)	Triglycerides (mg/dL)	Bile Acids (µmol/L)
I	0	Mean	151.45	3.46	116.49	62.33	55.50	9.45
I	0	±SD	2.38	0.25	3.23	11.83	23.98	6.84
II	0 (Reversal)	Mean	146.44	4.25	108.29	54.50	61.67	19.47
II	0 (Reversal)	±SD	1.79	0.72	1.36	7.94	21.18	4.61
III	250	Mean	150.56	3.40	116.70	61.83	34.17	10.43
III	250	±SD	2.83	0.24	2.31	12.34	30.18	4.89
IV	500	Mean	155.14	3.40	118.17	57.17	29.50	16.56
IV	500	±SD	2.71	0.41	3.34	8.47	21.25	8.24
V	1000	Mean	152.60	3.42	116.40	67.67	47.67	12.89
V	1000	±SD	1.99	0.37	2.34	13.71	10.89	5.57
VI	1000 (Reversal)	Mean	146.51	3.94	107.51	49.33	73.50	17.94
VI	1000 (Reversal)	±SD	2.37	0.34	2.31	5.43	23.39	7.91

GroupNumber	Dose (mg/kg)		Body Weight (g)	Brain	Liver	Kidneys	Adrenals	Testes	Prostate + Seminal Vesicle with Coagulation gland
I	0	Mean	280.650	1.816	9.772	2.048	0.044	3.072	1.615
I	0	±SD	9.586	0.071	0.920	0.132	0.007	0.305	0.509
II	0 (Reversal)	Mean	317.083	1.965	10.788	2.202	0.043	3.129	1.723
II	0 (Reversal)	±SD	9.912	0.148	0.774	0.175	0.006	0.422	0.300
III	250	Mean	271.200	1.857	10.199	2.168	0.045	2.717	1.426
III	250	±SD	15.134	0.042	1.763	0.167	0.006	0.284	0.233
IV	500	Mean	266.517	1.826	9.335	2.183	0.042	2.789	1.347
IV	500	±SD	16.073	0.073	2.362	0.293	0.002	0.203	0.259
V	1000	Mean	271.083	1.848	9.491	1.631	0.034	2.912	1.505
V	1000	±SD	13.814	0.074	1.316	0.209	0.005	0.393	0.191
VI	1000 (Reversal)	Mean	304.800	1.938	13.303	2.612	0.038	3.220	1.761
VI	1000 (Reversal)	±SD	8.866	0.115	1.590	0.171	0.005	0.254	0.199

GroupNumber	Dose (mg/kg)		Heart	Spleen	Thymus	Epididymides
I	0	Mean	1.178	1.328	0.305	0.865
I	0	±SD	0.076	0.295	0.051	0.098
II	0 (Reversal)	Mean	1.252	1.183	0.334	0.992
II	0 (Reversal)	±SD	0.171	0.149	0.056	0.124
III	250	Mean	1.086	1.056	0.423	0.835
III	250	±SD	0.088	0.232	0.121	0.030
IV	500	Mean	1.134	0.978	0.374	0.763
IV	500	±SD	0.186	0.397	0.091	0.050
V	1000	Mean	1.063	1.464	0.364	0.907
V	1000	±SD	0.196	0.732	0.032	0.154
VI	1000 (Reversal)	Mean	1.357	1.578	0.335	1.020
VI	1000 (Reversal)	±SD	0.157	0.471	0.059	0.106

Registration Dossier

Registration Dossier

Data platform availability banner - registered substances factsheets

Diss Factsheets

Oxacycloheptadec-10-en-2-one

Endpoint summary

Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

I

I

I

I

Parameters

Parameters

Endpoint conclusion

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint conclusion

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint conclusion

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint conclusion

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint conclusion

Additional information

Justification for classification or non-classification