Registration Dossier

Administrative data

Description of key information

Two studies are available to evaluate the acute toxicity of DGEBA diacrylate.
By oral and dermal routes, no mortality or severe clinical signs were observed in rats treated with 2000 mg/kg of DGEBA diacrylate.
No study by inhalation is available ; based on the low volatility of DGEBA diacrylate, the substance is considered to be not volatil, therefore this type of test is not required.

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:
From June 16 to July 08, 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
no data about purity and no certificate of analysis of the test substance
Principles of method if other than guideline:
Not applicable
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: Charles River (UK) Ltd., Manston, UK
- Age at study initiation: 5-8 weeks
- Weight at study initiation: Males: 142-174 g, females: 134-155 g
- Fasting period before study: Overnight
- Housing: Housed in groups of five by sex in solid-floor polypropylene cages with sawdust bedding
- Diet (e.g. ad libitum): Food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, UK), ad libitum
- Water (e.g. ad libitum): Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 °C
- Humidity (%): 47-75%
- Air changes (per hour): 15/hour
- Photoperiod (hours dark / hours light): 12 hours dark / 12 hours light
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg

DOSAGE PREPARATION (if unusual): Test material was freshly prepared as a suspension in arachis oil B.P. The preparation was heated to approximately 70 °C in water to ensure adequate mixing and allowed to cool before dosing.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Dose was selected based on a range-finding study conducted on 1 rat/sex/dose at 2000 mg/kg bw and animals were observed for 5 days.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Deaths and overt signs of toxicity were recorded at 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days; individual bodyweights were recorded on Day 0 (prior to dosing), 7 and 14
- Necropsy of survivors performed: Yes; surviving animals were killed by cervical dislocation and examined grossly
Statistics:
No data
Preliminary study:
In the range-finding study, no mortality or clinical signs of toxicity were observed (only one rat treated with 2000 mg/kg).
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 deaths were observed .
Clinical signs:
Animals appeared normal throughout the study period.
Body weight:
All animals showed expected gain in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 for DGEBA diacrylate is higher than 2000 mg/kg bw in rats therefore it is not classified for oral acute toxicity.
Executive summary:

In an acute oral toxicity (limit test) study performed in accordance with GLP and OECD guideline 401, groups (5/sex) of Sprague-Dawley rats were given a single oral dose of DGEBA diacrylate in arachis oil at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all macroscopically necropsied after sacrifice. A preliminary range-finding test was also conducted on 1 rat/sex/dose at 2000 mg/kg bw and animals were observed for 5 days. In this previous test, no mortality or clinical signs of toxicity were observed.

In the main study, no deaths were observed and animals appeared normal throughout the study period. All animals showed expected gain in bodyweight over the study period. No abnormalities were noted at necropsy. The combined oral LD50 was considered to be greater than 2000 mg/kg bw.

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 as reliable; the test was performed with the OECD guidelines (401).

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:
04 June 2014 -- 04 July 2014
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: within ± 20% of the mean body weight of all the study animals of the same sex (245 g for females and 412 g for males).
- Fasting period before study: No
- 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: 17 June 2014 to 04 July 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
- Washing: at 24h post-exposure, with a moistened cotton pad with acetone and then water for injection

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume: no
- For solids, paste formed: yes
Duration of exposure:
24 hr
Doses:
2000 mg/kg
No. of animals per sex per dose:
ten rats (five males + 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
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 mortality was observed in any animals.
Clinical signs:
No clinical signs indicative of systemic toxicity were observed in any animals.
No cutaneous reactions were observed in any males.
A very slight to well defined erythema at the application site was noted in all females from Day 2, 3 or 4 until Day 14 at the latest, along with dryness of the skin in 4/5 females from Day 4 until Day 14 at the latest. Scabs was noted in 3/5 females from Day 3 to Day 11 and wound in 1/5 females from Day 4 to Day 7.
Body weight:
When compared to CiToxLAB France historical control data, lower body weight gain was noted in 3/5 females (11, 13 and 14 g vs. 25 ± 10.0 g in control data base) between Day 1 and Day 8; and in 1/5 other females (3 g vs. 27 ± 11.1 g in control data base) between Day 8 and Day 15. Over the period from Day 1 to Day 15, 4/5 females had a lower body weight gain when compared to historical control data (18, 29, 30 and 37 g vs. 52 ± 12.9 g in control data base).

A lower body weight gain was also noted in 3/5 males (19, 34 and 35 g vs. 50 ± 12.0 g in control data base) between Day 8 and Day 15 and over the period from Day 1 to Day 15 when compared to CiToxLAB France historical control data (54, 67 and 75 g vs. 89 ± 12.8 g in control data base). However, the body weight of test-item treated males on Day 1 was significantly higher than the body weight of males in CiToxLAB France historical control data (mean body weight = 412 ± 15.8 g vs. 333 ± 10.3 g in control data base). This could explain that the body weight gain of test item-treated males was lowered in some animals.

The body weights of the other animals were unaffected by the test item treatment. (see Table 1)
Gross pathology:
There were no test item-related gross findings.
The irregular color noted in the lungs from 3/5 males treated at 2000 mg/kg/day was considered to be most probably unrelated with test item administration since this was not seen in females, and since this finding is occasionally seen in untreated rats of these strain, age, and supplier.
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

217 (± 10.3)

215 (± 7.6)

333 (± 10.3)

412 (± 15.8)

. Day 8

242 (± 10.6)

229 (± 7.1)

372 (± 9.5)

450 (± 16.5)

. Day 15

269 (± 13.0)

245 (± 6.2)

422 (± 12.6)

485 (± 25.5)

Body weight change

(mean (± SD))

 

 

 

 

. Days 1-8

+25 (± 10.0)

14 (± 2.2)

+39 (± 11.5)

37 (± 4.8)

. Days 8-15

+27 (± 11.1)

17 (± 8.9)

+50 (± 12.0)

35 (± 10.5)

. Days 1-15

+52 (± 12.9)

31 (± 8.5)

+89 (± 12.8)

72 (± 12.3)

SD: standard deviations.

Interpretation of results:
GHS criteria not met
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 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 the test item following a single dermal application to rats.

This study was based on the international guidelines (OECD No. 402 and Council Regulation No. 440/2008 of 30 May 2008, Part B.3) and was performed in compliance with the principles of Good Laboratory Practice.

 

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.

No cutaneous reactions were observed in any males.

A very slight to well-defined erythema at the application site was noted in all females from Day 2, 3 or 4 until Day 14 at the latest along with dryness of the skin in 4/5 females from Day 4 until Day 14 at the latest. Scabs were noted in 3/5 females from Day 3 to Day 11 and wound in 1/5 females from Day 4 to Day 7.

When compared to historical control data, lower body weight gain was noted in 3/5 females between Day 1 and Day 8; and in 1/5 other females between Day 8 and Day 15. Over the period from Day 1 to Day 15, 4/5 females had a lower body weight gain when compared to historical control data.

A lower body weight gain was also noted in 3/5 males between Day 8 and Day 15 and over the study period when compared to historical control data. However, the body weight of test-item treated males on Day 1 was significantly higher than the body weight of males in historical control data. This could explain that the body weight gain of test item-treated males was lowered in some animals.

The body weights of the other animals were unaffected by the test item treatment.

There were no test item-related gross findings.

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 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 as reliable; the test was performed with the OECD guidelines (402).

Additional information

Oral acute toxicity study (Walker 1993):

In an acute oral toxicity (limit test) study performed in accordance with GLP and OECD guideline 401, groups (5/sex) of Sprague-Dawley rats were given a single oral dose of DGEBA diacrylate in arachis oil at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all macroscopically necropsied after sacrifice. A preliminary range-finding test was also conducted on 1 rat/sex/dose at 2000 mg/kg bw and animals were observed for 5 days. In this previous test, no mortality or clinical signs of toxicity were observed.

In the main study, no deaths were observed and animals appeared normal throughout the study period. All animals showed expected gain in bodyweight over the study period. No abnormalities were noted at necropsy. The combined oral LD50 was considered to be greater than 2000 mg/kg bw.

Dermal acute toxicity study (Modeste 2014):

The objective of this study was to evaluate the potential toxicity of the test item following a single dermal application to rats (OECD 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. No cutaneous reactions were observed in any males. A very slight to well-defined erythema at the application site was noted in all females from Day 2, 3 or 4 until Day 14 at the latest along with dryness of the skin in 4/5 females from Day 4 until Day 14 at the latest. Scabs were noted in 3/5 females from Day 3 to Day 11 and wound in 1/5 females from Day 4 to Day 7.

When compared to historical control data, lower body weight gain was noted in 3/5 females between Day 1 and Day 8; and in 1/5 other females between Day 8 and Day 15. Over the period from Day 1 to Day 15, 4/5 females had a lower body weight gain when compared to historical control data.

A lower body weight gain was also noted in 3/5 males between Day 8 and Day 15 and over the study period when compared to historical control data. However, the body weight of test-item treated males on Day 1 was significantly higher than the body weight of males in historical control data. This could explain that the body weight gain of test item-treated males was lowered in some animals. The body weights of the other animals were unaffected by the test item treatment. There were no test item-related gross findings.

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

Justification for classification or non-classification

As LD50 for oral and dermal toxicity were higher than 2000 mg/kg bw in rats, DGEBA diacrylate is not classified according to the criteria of the CLP Regulation (EC) N° (1272-2008).