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Description of key information

An oral acute study is available on Tricyclodecane dimethacol dimethacrylate, no mortality was observed at the highest dose of 2000 mg/kg/day in rats.

No acute data by dermal route is available on Tricyclodecane dimethanol dimethacrylate. However data is available on an analogue substance : Tricyclodecane dimethanol diacrylate in which no mortality was observed at the highest dose of 2000 mg/kg in rats.

Acute studies on Tricyclodecane dimethanol diacrylate by oral and dermal route showed no death or severe clinical signes at the maximal dose of 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 2005 - November 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 1
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
yes
Remarks:
the temperature recorded in the animal room was sometimes outside of the target ranges specified in the Study Plan: minor deviation not considered to have compromised the validity and integrity of the study
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier, le Genest-Saint-Isle, France
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 week old
- Weight at study initiation: 196 +/- 8 g
- Fasting period before study: yes
- Housing: polycarbonate cages. 3 rats per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): 12 / hour
- Photoperiod (hrs dark / hrs light): 12h/12h
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The dosage form preparations were administered to the animals under a volume of 10 mL/kg.
The administration was performed in a single dose by oral route using a metal gavage tube fitted to a 2 mL plastic syringe.
The volume administered to each animal was adjusted according to body weight determined on the day of treatment.
Doses:
As no information on the toxic potential of the test item was available, for animal welfare reasons, the starting dose-level of 300 mg/kg was chosen.
1st dose : 300 mg/kg
2nd dose : 2000 mg/kg
No. of animals per sex per dose:
300 mg/kg : 3
2000 mg/kg : 3 + 3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations : after adminstration and at least once a day after
- Freqency of weighing: aon day 1, day 8 and day 15
- Necropsy of survivors performed: yes
Preliminary study:
no
Key result
Sex:
female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortality observed at 300 or 2000 mg/kg/day.
Clinical signs:
No clinical signs at 300 mg/kg/day.
Hypoactivity and piloerection observed in 3/6 animals treated with 2000 mg/kg/day on day 1 only.
Body weight:
When compared to historical control animals, a slightly reduced body weight gain was seen in 2/3 given 300 mg/kg during the second week of the study.
At the 2000 mg/kg dose-level, a reduced body weight gain was recorded in 1/6 females during the first week of the study and in 2/6 females during the second week of the study.
The overall body weight gain of the other animals was not considered to be affected by treatment with the test item.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.
Other findings:
no
Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the oral LD50 of the test item was higher than 2000 mg/kg/day.
Executive summary:

The acute oral toxicity of the test item was evaluated in rats according to the OECD guideline 423 and the GLP principles.

The test item was prepared in corn oil and was administered by oral route (gavage), under a volume of 10 mL/kg to groups of 3 fasted female Sprague-Dawley rats. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days following the single administration of the test item.

As no information on the toxic potential of the test item was available, for animal welfare reasons, the starting dose-level of 300 mg/kg was chosen. No mortality and clinical signs were observed at this dose. So two other groups were treated with 2000 mg/kg/day. No mortality occured but hypoactivity and piloerection were observed in 3/6 animals on day 1 only.

A slighlty reduced body weight gain was seen in 2/3 given 300 mg/kg during the second week of the study. At the 2000 mg/kg dose-level, a reduced body weight gain was recorded in 1/6 females during the first week of the study and in 2/6 females during the second week of the study. The overall body weight gain of the other animals was not considered to be affected by treatment with the test item.

At necropsy, no apparent abnormalities were observed in any animal.

Under the experimental conditions of this study, the oral LD50 of the test item was higher than 2000 mg/kg/day.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The acute oral study is considered to be reliable.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 January 2014 -- 21 March 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 1
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: 348 g (range: 341 g to 361 g) for the males and 235 g (219 g to 254 g) for the females
- Housing: polycarbonate cages with stainless steel lids
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: 04 March 2014 to 21 March 2014
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 10% of body surface, dorsal site
- Type of wrap if used: hydrophilic gauze pad + adhesive hypoallergenic aerated semi-occlusive dressing + restraining bandage

REMOVAL OF TEST SUBSTANCE
- Removal of dressing: 24h post-exposure

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume: no
Duration of exposure:
24 hr
Doses:
2000 mg/kg
No. of animals per sex per dose:
Ten rats (five males and five nulliparous and non pregnant females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment, on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).
Statistics:
no
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Mortality:
No unscheduled deaths occurred during the study.

Clinical signs:
No clinical signs indicative of systemic toxicity were observed in any animals.
A very slight to moderate-to-severe erythema was noted in all males and a very slight to well defined erythema was recorded in all females from Day 2 until Day 6 at the latest. This was associated with very slight to moderate dryness from Day 4 or 5 until Day 13 at the latest in all animals. Scabs were observed in 2/5 males from Day 7 to Day 11.
Body weight:
When compared to historical control data, a higher body weight gain was observed in one male (+57 g vs. +39 ± 11.5 g in control data base) between Days 1 and 8 whereas a lower body weight gain was noted in two males (+35 g and +33 g, respectively, vs. +50 ± 12.0 g in control data base) between Day 8 and Day 15.
A lower body weight gain was observed in two females (+13 g and +14 g, respectively, vs. +25 ± 10.0 g in control data base) between Days 1 and 8. This was followed by a body weight loss of 2 g in one female over the second part of the observation period.
Nevertheless and in absence of marked body weight effect, body weight of animals was considered unaffected by the test item treatment in both sexes when compared to historical control data.
Gross pathology:
The spleen was enlarged in 4/5 males given the test item at 2000 mg/kg. In the absence of macroscopic findings in females given the same dose-level, this finding was considered to be incidental and unrelated to the test item administration.
Other findings:
no
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP Regulation
Conclusions:
Under the experimental conditions of this study, the dermal LD50 of the test item, was higher than 2000 mg/kg in rats.
Therefore, the test item should not be classified as acutely toxic by dermal route according to the criteria of the CLP Regulation.
Executive summary:

The objective of this study was to evaluate the potential toxicity of the test item, following a single dermal application to rats.

This study was conducted in compliance with OECD Guideline No. 402 and the principles of Good Laboratory Practices.

 

Methods

The test item was applied in its original form to the skin of five female then five male Sprague-Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by a semi-occlusive dressing for 24 hours.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. From Day 2, any local reactions at the treatment site were also noted. Body weight was recorded on Day 1 and then on Days 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination.Macroscopic lesions were preserved in buffered formal in then destroyed at the finalization of the study report as no microscopic examination was performed.

 

Results

No unscheduled deaths occurred during the study.

No clinical signs indicative of systemic toxicity were observed in any animals.

A very slight to moderate-to-severe erythema was noted in all males and a very slight to well-defined erythema was recorded in all females from Day 2 until Day 6. This was associated with very slight to moderate dryness from Day 4 or 5 until Day 13 in all animals. Scabs were observed in 2/5 males from Day 7 to Day 11.

When compared to CiToxLAB France historical control data, a higher body weight gain was observed in 1/5 males (+57 g vs. +39 ± 11.5 g in control data base) between Days 1 and 8 whereas a lower body weight gain was noted in 2/5 males (+35 g and +33 g, respectively, vs. +50 ± 12.0 g in control data base) between Day 8 and Day 15.

A lower body weight gain was observed in 2/5 females (+13 g and +14 g, respectively, vs. +25 ± 10.0 g in control data base) between Days 1 and 8. This was followed by a body weight loss of 2 g in one of them over the second part of the observation period.

Nevertheless and in absence of marked body weight effect, body weight of animals was considered unaffected by the test item treatment in both sexes when compared to CiToxLAB France historical control data.

At the end of the observation period, there were no macroscopic findings at necropsy attributable to the test item administration.

 

Conclusion

Under the experimental conditions of this study, the dermal LD50 of the test item, was higher than 2000 mg/kg in rats.

 

Therefore, the test item should not be classified as acutely toxic by dermal route according to the criteria of the CLP Regulation.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The acute dermal study is considered to be reliable.

Additional information

Read-across : Acute oral study (Papineau 2014)

The objective of this study was to evaluate the potential acute toxicity of the test item, following a single oral administration (gavage) to rats (OECD guideline 423). The test item, was administered once by oral route (gavage) to three groups of three fasted female Sprague-Dawley rats under a dosage-volume of 10 mL/kg. The test item was prepared in corn oil.

Since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data have been taken into account by the Sponsor, the starting dose-level was 300 mg/kg for ethical reasons. After the first assay, the next higher dose-level of 2000 mg/kg was tested. Then, as no toxicity was observed at this higher dose-level, the results were confirmed in other three females. Each animal was observed at least once a day for mortality and clinical signs for 15 days. Body weight was recorded on Day 1 and then on Days 8 and 15.

No unscheduled deaths occurred during the study and no clinical signs were observed in any animals.

When compared to the historical control data, a lower body weight gain was noted in 2/6 females given 2000 mg/kg (+7 g vs.+20 g ± 6.7 g in control data base) between Day 8 and Day 15. A higher body weight gain was observed in 1/6 females (+30 g vs.+20 g ± 6.7 g in control data base) given 2000 mg/kg over the same period.

Nevertheless,compared to the historical control data, the body weight of the animals was considered to be unaffected by the test item treatment.

No test item-related macroscopic post-mortem findings were noted.

Under the experimental conditions of this study, the oral LD50 of the test item, was higher than 2000 mg/kg in rats.

Read-across: Acute dermal study (Papineau 2014)

The objective of this study was to evaluate the potential toxicity of the test item, following a single dermal application to rats (OECD guidelaine 402).

The test item was applied in its original form to the skin of five female then five male Sprague-Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by a semi-occlusive dressing for 24 hours.

No unscheduled deaths occurred during the study. No clinical signs indicative of systemic toxicity were observed in any animals. A very slight to moderate-to-severe erythema was noted in all males and a very slight to well-defined erythema was recorded in all females from Day 2 until Day 6. This was associated with very slight to moderate dryness from Day 4 or 5 until Day 13 in all animals. Scabs were observed in 2/5 males from Day 7 to Day 11.

When compared to historical control data, a higher body weight gain was observed in 1/5 males (+57 g vs.+39 ± 11.5 g in control data base) between Days 1 and 8 whereas a lower body weight gain was noted in 2/5 males (+35 g and +33 g, respectively,vs.+50 ± 12.0 g in control data base) between Day 8 and Day 15. A lower body weight gain was observed in 2/5 females (+13 g and +14 g, respectively,vs.+25 ± 10.0 g in control data base) between Days 1 and 8. This was followed by a body weight loss of 2 g in one of them over the second part of the observation period.

Nevertheless and in absence of marked body weight effect,body weight of animals was considered unaffected by the test item treatment in both sexes when compared to historical control data.

At the end of the observation period, there were no macroscopic findings at necropsy attributable to the test item administration.

Under the experimental conditions of this study, the dermal LD5of the test item, was higher than 2000 mg/kg in rats.

 

Justification for classification or non-classification

Based on the data available, Tricyclodecane dimethanol dimethacrylate is not classified in the acute toxicity endpoint according to the Regulation EC no.1272/2008.