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Administrative data

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:
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.