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Administrative data

Description of key information

The potential of acute toxicity of 1,10-decanediol diacrylate was evaluated in two studies, one by oral route and one by dermal route. 
No mortalities were showed in both studies; the oral and dermal LD50 were higher than 2000 mg/kg in rats.
No data is available by inhalation on 1,10-decanediol diacrylate. However a data is available on an analoguous substance, hexamethylene diacrylate, which shows a LC50 higher than 0.41 mg/L.

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:
15 April 2013 - 17 June 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
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: 211 g (range: 192 g to 223 g)
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages
- 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: 14 May 2013 to 11 June 2013
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 or 200 mg/mL
- Justification for choice of vehicle: as unsatisfactory solubility of the test item was obtained in drinking water treated by reverse osmosis, under similar experimental conditions (i.e. heterogeneous emulsion at the concentration of 200 mg/mL was obtained), another vehicle was chosen from the following organic solvents (in order of preference): 0.5% methylcellulose aqueous solution and corn oil. A solution was obtained at the concentration of 200 mg/mL in corn oil.
- Maximum dose-volume applied: 10 mL/kg

DOSAGE PREPARATION : Fresh dose formulations were prepared by the CiToxLAB France Pharmacy on the day of each administration and kept at room temperature and protected from light prior to administration.

CLASS METHOD :
- Rationale for the selection of the starting dose: since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data were taken into account by the Sponsor, the starting dose-level was 300 mg/kg for ethical reasons.
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
nulliparous and non-pregnant females.
300 mg/kg : 3 females
2000 mg/kg: 3 + 3 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: the day of group allocation, just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).
Statistics:
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 unscheduled deaths occurred during the study.

Clinical signs:
No clinical signs were observed in any animals.
Body weight:
The mean body weights and mean body weight changes (g) recorded in test item-treated animals during the observation period and in CiToxLAB France historical control data are summarized in the Table 1.
Body weight was unaffected by the test item treatment, when compared to historical control data.
Gross pathology:
There were no findings considered to be related to the test item administration.
The few macroscopic findings noted at the end of the observation period (dilatation of the uterus, brown discoloration of the lungs) were of those commonly recorded in the rat and none were considered to be related to the test item administration.
Other findings:
no

Table 1

 

Sex

Female

Group

Historical control data

1

2

3

Dose-level (mg/kg)

0

300

2000

2000

Body weight (mean (± SD))

 

 

 

 

. Day 1

208 (± 11.7)

219 (± 4.5)

214 (± 1.5)

199 (± 7.0)

. Day 8

246 (± 12.7)

257 (± 4.7)

256 (± 8.5)

243 (± 8.7)

. Day 15

266 (± 14.0)

281 (± 5.8)

280 (± 3.8)

256 (± 9.6)

Body weight change (mean (± SD))

 

 

 

 

. Days 1-8

+39 (± 5.1)

+39 (± 6.0)

+41 (± 9.6)

+44 (± 4.0)

. Days 8-15

+20 (± 6.3)

+24 (± 8.0)

+24 (± 8.7)

+13(± 2.1)

. Days 1-15

+58 (± 5.8)

+62 (± 2.6)

+65 (± 5.1)

+57 (± 5.8)

SD: standard deviations.

 

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the oral LD50 of 1,10-decanediol diacrylate was higher than 2000 mg/kg in rats.

Executive summary:

The objective of this study was to evaluate the potential acute toxicity of 1,10-decanediol diacrylate following a single oral administration (gavage) to rats. This study was conducted in compliance with OECD Guideline No. 423 and the principles of Good Laboratory Practices.

 

Methods

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 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.

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 formalin then destroyed at the finalization of the study report as no microscopic examination was performed.

Results

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

Body weight gain was unaffected by the test item treatment, when compared to historical control data.

The test item administration did not induce any macroscopic findings at necropsy.

Conclusion

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

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

 

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The oral acute study is considered to be a reliable study (klimisch score of 1).

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
no guideline followed
Principles of method if other than guideline:
BASF-Test: The inhalation hazard test demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at the temperature chosen for vapor generation (usually 20°C). Several groups of usually 3 rats per sex were sequentially exposed to the vapors, generated by bubbling 200 l/h air through a substance column of about 5 cm above a fritted disc in a glass cylinder for different time periods.
No analytical determination of the atmosphere concentrations was performed. The nominal concentration usually can be calculated as quotient of the amount of the test substance weight loss during exposure. Group-wise documentation of clinical signs was performed over the 14 day study period. Body weight of groups was determined before the start of the study and at the end of the observation period in surviving animals.
GLP compliance:
no
Remarks:
; GLP was not compulsory at the time the study was conducted
Test type:
other: Inhalation hazard test
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation:
mean body weight, males: 184.2 g in the treated group
mean body weight, males: 200 g in the control group
mean body weight, females: 200 g in the treated group
mean body weight, females: 194 g in the control group
- Diet: Herilan MRH-Haltung; H. Eggersmann KG (ad libitum)
- Water: ad libitum
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: The animals were exposed to atmosphere saturated with the volatile parts of the test material in the air at 20 °C.
Details on inhalation exposure:
Saturation of the atmosphere was generated by conducting an air stream through a substance layer of 5 cm height.
The rats were exposed to the test atmosphere for 7 hours.
Air flow was 200 l/h in the exposure chamber.
The control animals were shame-exposed.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
7 h
Concentrations:
The concentration was 0.41 mg/l (20 °C), the nominal concentration was calculated as quotient of the amount of the test substance weight loss during exposure.
No. of animals per sex per dose:
3 animals per sex per group
Control animals:
no
Details on study design:
The exposure time not causing lethality was tested twice.
- Duration of post exposure period until necropsy: 14 days
- Frequency of weighing: Test animals were weighed at test initiation only
- Frequency of observations: The animals were observed following exposure after 3 min, 10 min, 30 min, 1 hour, 3 hours, 7 hours and thereafter daily for the first 3 days after test initiation
- Necropsy of survivors performed: yes. The necropsy of the animals was done on day 14 following exposure
Statistics:
no
Preliminary study:
no data
Key result
Sex:
male/female
Dose descriptor:
LC0
Effect level:
0.41 mg/L air
Exp. duration:
7 h
Remarks on result:
other: All 12 animals exposed to the test material survived.
Mortality:
All animals exposed to the test material survived, as well as all controls.
Clinical signs:
In both treated groups, accelerated intermittent breathing, snout-wiping and unkempt fur were reported during and after exposure; at day 3 of observation, no more symptoms were seen. Therefore the animals were no more observed until day 14, i.e. the day of necropsy.
Controls were inconspicuous.
Body weight:
Only initial body weights were recorded.
Gross pathology:
Necropsy of the animals sacrificed on day 14 was inconspicuous.
Other findings:
no
Interpretation of results:
GHS criteria not met
Conclusions:
Based on these results, the LC50 is considered to be higher 0.41 mg/L.
Executive summary:
Sprague Dawley rats were exposed to atmosphere saturated with the volatile parts of the test material Hexamethylene Diacrylate (technical grade, purity ca. 90%) at 20 °C for 7 hours. The test concentration was 0.41 mg/l air. All 12 animals survived. Clinical symptoms consisted of accelerated intermittent breathing, snout-wiping and unkempt fur and were seen during and after exposure for 3 days, the symptoms were indicative for respiratory irritation. Necropsy of the animals sacrificed on day 14 was inconspicuous.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
0.41 mg/m³
Quality of whole database:
The inhalation acute study is considered to be a reliable study (klimisch score of 2).

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:
15 April 2013 - 13 June 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
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: the males had a mean body weight of 352 g (range: 340 g to 361 g) and the females had a mean body weight of 233 g (range: 223 g to 243 g).
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages
- 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: 21 May 2013 to 07 June 2013
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
- Washing: none

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume: no
Duration of exposure:
24h
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 on the day of group allocation: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).
Statistics:
no
Key result
Sex:
male/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 unscheduled deaths occurred during the study.

Clinical signs:
Chromodacryorrhea was observed in 1/5 males on days 7 and 8. As this clinical sign was of isolated occurrence, this was considered as incidental.
Erythema (very slight to severe) and edema (very slight or slight) were noted on application site of all male and female animals from day 2 up to day 7 at the latest.
These findings were associated with dryness of the skin (very slight or slight) at application site of all males and at application site of 4/5 females from day 4 up to day 15 at the latest.
In addition, desquamation was noted in 2/5 females from day 4 to day 13 or 14.
Scabs on application site were also observed in 1/5 males and 1/5 females between day 5 and day 7.
Body weight:
The mean body weights and the mean body weight changes (g) recorded in test item-treated animals during the observation period and in historical control data are summarized in the Table 1.
Body weight of animals was unaffected by the test item treatment when compared to historical control data.
Gross pathology:
There were no findings considered to be related to the test item administration.
The few macroscopic findings noted at the end of the treatment period (deformation and strangling of the spleen in a single male at 2000 mg/kg) were considered to be fortuitous.
Other findings:
no

Table 1. 

Sex

Female

Male

Group

historical control data

1

historical control data

2

Dose-level (mg/kg)

0

2000

0

2000

Body weight (mean (± SD))

 

 

 

 

. Day 1

236 (± 8.9)

233 (± 8.1)

362 (± 12.0)

352 (± 7.9)

. Day 8

253 (± 12.0)

250 (± 8.2)

394 (± 15.3)

383 (± 9.6)

. Day 15

273 (± 16.3)

275 (± 8.4)

441 (± 21.5)

430 (± 14.9)

Body weight change (mean (± SD))

 

 

 

 

. Days 1-8

+17 (± 11.0)

+18 (± 8.6)

+32 (± 9.1)

+31 (± 3.6)

. Days 8-15

+20 (± 7.1)

+25 (± 2.8)

+47 (± 7.5)

+47 (± 7.2)

. Days 1-15

+37 (± 16.3)

+42 (± 6.5)

+79 (± 15.6)

+78 (± 9.5)

SD: standard deviations.

 

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the dermal LD50 of 1,10-decanediol diacrylate was higher than 2000 mg/kg in rats.
Therefore, the test item should not be classified as harmful or toxic by dermal route according to the criteria of CLP Regulation.
Executive summary:

The objective of this study was to evaluate the potential toxicity of 1,10-decanediol diacrylate 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 formalin 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.

 

Erythema and edema were noted on application site of all male and female animals from day 2 up to day 7 at the latest. These findings were associated with dryness of the skin at application site of all males and at application site of 4/5 females from day 4 up to day 15 at the latest.

In addition, desquamation was noted in 2/5 females from day 4 to day 13 or 14.

Scabs on application site were also observed in 1/5 males and 1/5 females between day 5 and day 7.

Body weight of animals was unaffected by the test item treatment when compared to historical control data.

The test item administration did not induce any macroscopic findings at necropsy.

Conclusion

Under the experimental conditions of this study, the dermal LD50 of 1,10-decanediol diacrylate was higher than 2000 mg/kg in rats.

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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The dermal acute study is considered to be a reliable study (klimisch score of 1).

Additional information

Acute toxicity: oral (Papineau 2013)

The objective of this study was to evaluate the potential acute toxicity of 1,10-decanediol diacrylate following a single oral administration (gavage) to rats. This study was conducted in compliance with OECD Guideline No. 423 and the principles of Good Laboratory Practices.

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 females.

No unscheduled deaths occurred during the study and no clinical signs were observed in any animals. Body weight gain was unaffected by the test item treatment, when compared to historical control data. The test item administration did not induce any macroscopic findings at necropsy.

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

Acute toxicity: inhalation (read-across with HDDA)

Sprague Dawley rats were exposed to atmosphere saturated with the volatile parts of the test material Hexamethylene Diacrylate (technical grade, purity ca. 90%) at 20 °C for 7 hours. The test concentration was 0.41 mg/l air. All 12 animals survived. Clinical symptoms consisted of accelerated intermittent breathing, snout-wiping and unkempt fur and were seen during and after exposure for 3 days, the symptoms were indicative for respiratory irritation. Necropsy of the animals sacrificed on day 14 was inconspicuous. Based on these results, the LC50 is considered to be higher 0.41 mg/L.

Acute toxicity: dermal (Papineau 2013)

The objective of this study was to evaluate the potential toxicity of 1,10-decanediol diacrylate 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.

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.

Erythema and edema were noted on application site of all male and female animals from day 2 up to day 7 at the latest. These findings were associated with dryness of the skin at application site of all males and at application site of 4/5 females from day 4 up to day 15 at the latest.

In addition, desquamation was noted in 2/5 females from day 4 to day 13 or 14.

Scabs on application site were also observed in 1/5 males and 1/5 females between day 5 and day 7.

Body weight of animals was unaffected by the test item treatment when compared to historical control data.

The test item administration did not induce any macroscopic findings at necropsy.

Under the experimental conditions of this study, the dermal LD50 of 1,10-decanediol diacrylate was higher than 2000 mg/kg in rats.



Justification for classification or non-classification

No mortality or severe clinical signs was observed in the acute toxicity studies performed at the limit dose, after oral, dermal and inhalation exposure.

Therefore 1,10 -decanediol diacrylate is not classified for acute toxicity according to the Regulation EC 1272/2008.