3,3-dimethyl-8,9-dinorbornan-2-one

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

NOAEL was estimated to be 942.5 mg/kg bw when Sprague- Dawley male and female rats were orally exposed with 3,3-Dimethyl-8,9-dinorbornan-2-one.  

Based on the above study and predictions on 3,3-Dimethyl-8,9-dinorbornan-2-one and its read across substances, it can be concluded that NOAEL value is 942.5 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, 3,3-Dimethyl-8,9-dinorbornan-2-one can be not classified for reproductive toxicity.    

Link to relevant study records

Reference

Endpoint:

toxicity to reproduction

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Vehicle:

corn oil

Details on exposure:

not specified

Details on mating procedure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

61 ± 10.0 days

Frequency of treatment:

7 per week

Details on study schedule:

not specified

Dose / conc.:

942.5 mg/kg bw/day

No. of animals per sex per dose:

12

Control animals:

yes, concurrent vehicle

Details on study design:

not specified

Positive control:

not specified

Parental animals: Observations and examinations:

not specified

Oestrous cyclicity (parental animals):

not specified

Sperm parameters (parental animals):

not specified

Litter observations:

not specified

Postmortem examinations (parental animals):

not specified

Postmortem examinations (offspring):

not specified

Statistics:

not specified

Reproductive indices:

not specified

Offspring viability indices:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

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:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Dose descriptor:

NOAEL

Effect level:

942.5 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

reproductive performance

Remarks on result:

other: No effect observed

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

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:

not specified

Urinalysis findings:

not specified

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

Other effects:

not specified

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Dose descriptor:

other: not specified

Generation:

other: not specified

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Reproductive effects observed:

not specified

Treatment related:

not specified

Relation to other toxic effects:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and "l" )  and ("m" and "n" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Carbonyl compound OR Ketone by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Carbonyl, aliphatic attach [-C(=O)-] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Tertiary Carbon by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Cycloketone OR Overlapping groups OR Terpenes by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alkane, branched with tertiary carbon OR Bicycloheptane  OR Bridged-ring carbocycles OR Cycloalkane OR Cycloketone OR Terpenes by Organic Functional groups ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Known precedent reproductive and developmental toxic potential AND Piperazine-, dioxane-, morpholine-, tetrahydrothiopyran-like derivatives and cyclohexanamine (17c) by DART scheme v.1.0

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Inorganic chemical OR Not covered by current version of the decision tree by DART scheme v.1.0

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Alkali Earth by Groups of elements

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N by Chemical elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Carbonyl compound AND Ketone by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.245

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.77

Conclusions:

The NOAEL was estimated to be 942.5 mg/kg bw when Sprague- Dawley male and female rats were orally exposed with 3,3-Dimethyl-8,9-dinorbornan-2-one.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for 3,3-Dimethyl-8,9-dinorbornan-2-one. The NOAEL was estimated to be 942.5 mg/kg bw when Sprague- Dawley male and female rats were orally exposed with 3,3-Dimethyl-8,9-dinorbornan-2-one.  

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

942.5 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Reproductive toxicity:

In different studies, 3,3-Dimethyl-8,9-dinorbornan-2-one has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimation in rodents, i.e. most commonly in rats for 3,3-Dimethyl-8,9-dinorbornan-2-one along with the study available on structurally similar read across substance D-Camphor (CAS 464-49-3) and Camphor (CAS 76-22-2), The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for 3,3-Dimethyl-8,9-dinorbornan-2-one. The NOAEL was estimated to be 942.5 mg/kg bw when Sprague- Dawley male and female rats were orally exposed with 3,3-Dimethyl-8,9-dinorbornan-2-one.  

In another experimental study conducted by NTP (National Toxicology program (NTP), March 1992) on structurally similar read across substance D-Camphor (CAS 464-49-3), Sprague Dawley female rats were treated with D-Camphor in the concentration of 0, 100, 400 and 800 mg/kg bw/day orally by gavage for 10 days (gd 6-15). No mortality was observed in treated dams as compared to control. Decreased weight gain during the treatment period was observed in treated female rats as compared to control. Although maternal body weights in all treatment groups were within 5% of control values at all gestational ages, maternal weight gain during the treatment period in the 800 mg/kg/day group was significantly reduced. Food consumption was initially suppressed at 400 and 800 mg/kg/day. But recovered to control levels by the end of the treatment period. No effect on food consumption was observed at 100 mg/kg/day. Increased maternal water consumption during one or more of the following measurement periods (gd 6 to 9; gd 12 to 15; gd 15 to 18) was observed. Similarly, No effect on reproductive performance or fetal growth was observed in treated rats as compared to control. Absolute and relative liver weights exhibited a significant dose-related increase, but did not exceed 10% of control values in any individual group. In addition, No effect on viability of fetus was observed as compared to control. No external, visceral and skeletal malformations were observed in pups as compared to control. Therefore, NOAEL was considered to be 800 mg/kg bw for P and F1 generation when Sprague Dawley and female rats were treated with D-Camphor orally by gavage for 10 days (gd 6-15).

Further supported by experimental study conducted by Somadeet al(Experimental and Toxicologic Pathology, Volume 69, Issue 2, February 2017, Pages 99-108) on structurally similar read across substance Camphor (CAS 76-22-2), Wistar male rats were treated with Camphor in the concentration of 0, 0 (vehicle control),1000, 2000, 4000, and 6000 mg/kg orally by gavage for 7 days. No visible lesions were observed in Histopathology of testis as compared to control. Therefore, NOAEL was considered to be 6000 mg/kg bw for P generation when Westar rats were treated with Camphor orally by gavage for 7 days.

Thus, based on the above study and predictions on 3,3-Dimethyl-8,9-dinorbornan-2-one and its read across substances, it can be concluded that NOAEL value is 942.5 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, 3,3-Dimethyl-8,9-dinorbornan-2-one can be not classified for reproductive toxicity. 

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the above study and predictions on 3,3-Dimethyl-8,9-dinorbornan-2-one and its read across substances, it can be concluded that NOAEL value is 942.5 mg/kg bw with no effect on reproduction. Thus, as per criteria of CLP regulation, 3,3-Dimethyl-8,9-dinorbornan-2-one can be not classified for reproductive toxicity.