1,10-decanediyl diacrylate

Endpoint summary

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. 

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

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system 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:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occurred during the study.

Mortality:

No unscheduled deaths occurred during the study.

Clinical signs:

other: No clinical signs were observed in any animals.

Body weight:

other body weight observations

Remarks:

Body weight gain was unaffected by the test item treatment, when compared to historical control data (see table 1).

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/Body weight and Body weight changes

 

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 test conditions of this study, the oral LD50 of 1,10-decanediol diacrylate was higher than 2000 mg/kg in rats. Therefore, the substance is not classified according to the Annex I of the Regulation EC No. 1272/2008 (CLP).

Executive summary:

In an acute oral toxicity study performed according to OECD Guideline 423 and in compliance with GLP the test item, 1,10-decanediol diacrylate, 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. 

 

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. Therefore, 1,10-decanediol diacrylate is not classified according to the Annex I of the Regulation EC No. 1272/2008 (CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

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

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:

15 April 2013 - 13 June 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system 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:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occurred during the study.

Mortality:

No unscheduled deaths occurred during the study.

Clinical signs:

other: 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.

Body weight:

other body weight observations

Remarks:

Body weight of animals was unaffected by the test item treatment when compared to historical control data (see table 1).

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:

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.

Table 1/Body weight and body weight changes

 

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 is not classified according to the Annex I of the Regulation EC No. 1272/2008 (CLP).

Executive summary:

In an acute dermal toxicity study performed according to OECD Guideline No.402 and in compliance with GLP the test item, 1,10-decanediol diacrylate, 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.

 

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. Therefore, 1,10-decanediol diacrylate is not classified according to the Annex I of the Regulation EC No. 1272/2008 (CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

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

One study was available and considered as key study (CitoxLab 2013c). In this acute oral toxicity study performed according to OECD Guideline 423 and in compliance with GLP, the test item 1,10-decanediol diacrylate, 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. 

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. 

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: dermal

One study was available and considered as key study (CitoxLab 2013d). In this acute dermal toxicity study performed according to OECD Guideline No.402 and in compliance with GLP, the test item 1,10-decanediol diacrylate, 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.

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

Acute toxicity (Oral):

Based on the available information, the substance is not classified according to the Regulation (EC) No. 1272/2008 (CLP) criteria as the oral LD50 is higher than 2000 mg/kg bw.

Acute toxicity (dermal):

Based on the available information, the substance is not classified according to the Regulation (EC) No. 1272/2008 (CLP) criteria as the dermal LD50 is higher than 2000 mg/kg bw.

Acute toxicity (inhalation):

No information was available. Therefore, no classification is required according to the Regulation (EC) No. 1272/2008 (CLP) criteria.