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Administrative data

Description of key information

Acute oral toxicity: LD50 (rat, combined) >= 2000 mg/kg bw; OECD Guideline 401
Acute inhalation toxicity: no relevant route of exposure
Acute dermal toxicity: LD50 (rat) > 2000 mg/kg bw (read-across with Ethyltriglycol methacrylate)

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:
1999-04-09 - 1999-06-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, GLP
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Species, strain: rat, Sprague-Dawley ICO: OFA-SD (lOPS Caw).
Reason for this choice: rodent species generally accepted by regulatory authorities for this type of study.
Breeder: Iffa Credo, 69210 L'Arbresle, France.
Number and sex: one group of ten animals (five males and five females).
Age/weight: on the day of treatment, the animals were approximately 6 weeks old, and had a
mean body weight ± standard deviation of 196 ± 8 g for the males and 163 ± 7 g for the females.
Acclimatization: at least 5 days before the beginning of the study.
Identification of the animals: the animals were identified individually by earmarks or earnotches.

Environmental conditions
During the acclimatization period and throughout the study, the conditions in the animal room were set as follows:
· temperature: 21 ± 2°C
· relative humidity: 30 to 70%
· light/dark cycle: 12 h/12 h
· ventilation: approximately 12 cycles/hour of filtered, non-recycled air.
The temperature and relative humidity were under continuous control and recording. The records were checked daily and filed. In addition to these
daily checks, the housing conditions and corresponding instrumentation and equipment are verified and calibrated at regular intervals.
The animals were housed in polycarbonate cages (48 cm x 27 cm x 20 cm). Each cage contained four to seven animals of the same sex during the
acclimatization period and five rats of the same sex during the treatment period.
Each cage contained dust-free sawdust (SICSA, 94142 Alfortville, France).
Bacteriological and chemical analyses of the sawdust, including the detection of possible contaminants (pesticides, heavy metals), are performed regularly by external laboratories.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Fasting of the animals
The animals were fasted for an overnight period of approximately 18 hours before dosing, but had free access to water.
Food was given back approximately 4 hours after administration of the test substance.
Administration of the test substance
A preliminary test was conducted on a reduced number of animals in order to define the range of doses to be tested. The results of this preliminary test, not included in the report, enabled us to perform a limit test by administering 2000 mg/kg of the test substance to one group of
ten animals (five males and five females).
The test substance was administered undiluted, taking into consideration its specific gravity (0.96 glml).
The administration was performed in a single dose by oral route using a metal gavage tube fitted to a 1 ml plastic syringe (0.01 ml graduations).
The volume administered to each animal was adjusted according to body weight determined on
the day of treatment
Chronology of the study
The single administration was performed on 9 April 1999 in the morning (day 1) and was
Doses:
2000 mg/kg
No. of animals per sex per dose:
One group of ten animals (five males and five females).
Control animals:
no
Details on study design:
CLINICAL EXAMINATIONS
Clinical signs and mortality
The animals were observed frequently during the hours following administration of the test substance, for detection of possible treatment-related
clinical signs. Thereafter, observation of the animals was made at least once a day until day 15.
Type, time of onset and duration of clinical signs were recorded for each animal individually.
Time of death was recorded individually, in terms of the number of hours or days after dosing.

Body weight
The animals were weighed individually just before administration of the test substance on day 1 and then on days 8 and 15.
The body weight gain of the treated animals was compared to that of CIT control animals with the same initial body weight.

NECROPSY
On day 15, all animals were killed by carbon dioxide asphyxiation and a macroscopic examination was performed.
After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs,
pancreas, spleen and any other organs with obvious abnormalities) was performed.
In case of macroscopic lesions, organ samples were taken and preserved in 10% buffered formalin.
Preliminary study:
A preliminary test was conducted on a reduced number of animals in order to define the range of doses to be tested. The results of this preliminary test, not included in the report, enabled to perform a limit test by administering 2000 mg/kg of the test substance to one group of ten animals (five males and five females).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no death occured
Clinical signs:
Hypoactivity and piloerection were observed in all animals on day 1. Recovery was complete in all animals on day 2.
Body weight:
The body weight gain of the treated animals was similar to that of historical control animals
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Dose

(mg/l)

Time

Animals

Mortality

Clinical signs

Males

Females

2000

30 min

01-02-03-04-05-06

06-07-08-09-10

No

None

 

1h-2h-4h

01-02-03-04-05-06

06-07-08-09-10

No

Hypoactivity, piloerection

 

D2 to D15

01-02-03-04-05-06

06-07-08-09-10

No

None

Individual and mean body weight and weekly body weight change

Dose

mg/kg

Volume

ml/kg

Sex

Animals

Days

1

(1)

8

(1)

15

2000

2.09

Male

01

207

61

268

34

302

 

 

 

02

187

67

254

52

306

 

 

 

03

200

74

274

34

308

 

 

 

04

191

70

261

45

306

 

 

 

05

193

83

276

54

330

 

 

 

M

196

71

267

44

310

 

 

 

SD

8

8

9

10

11

 

 

 

 

 

 

 

 

 

2000

2.09

Female

01

168

43

211

15

226

 

 

 

02

151

44

195

16

211

 

 

 

03

163

43

206

24

230

 

 

 

04

164

45

209

20

229

 

 

 

05

167

37

204

25

229

 

 

 

M

163

42

205

20

225

 

 

 

SD

7

3

6

5

8

(1)   = Body weight gain

M = Mean

SD = Standard deviation

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 > 2000 mg/kg
Executive summary:

In an acute oral toxicity study according to OECD guideline 401 (adopted February, 24 1987), one group of fasted, ca.. 6 weeks old, Sprague Dawley rats (5/sex) were given a single oral dose of Butyldiglycol methacrylate at doses of 2000 mg/kg bw and observed for 14 days.

No deaths occurred at 2000 mg/kg. Hypoactivity and piloerection were observed in all animals on day 1. Recovery was complete in

all animals on day 2. LD50: > 2000 mkg bw

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
One relevant, reliable (Klimisch score = 1) and adequate study is available.

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:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
02.11.2011-27.12.2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Gudeline study OECD 402, GLP.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
2009-04-06
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: WISTAR rats Cr!: WI(Han) (full baITier)
- Number of animals: 5 male and 5 female
- Age at study initiation: males: approximately 9 weeks old, females: approximately 13 weeks old
- Weight at study initiation: males: 236 - 249 g; females: 208 - 220 g.
- Fasting period before study: no
- Housing: separately in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding. Full barrier in an air-conditioned room
- Diet (e.g. ad libitum): Altromin 1324 maintenance diet for rats and mice, ad libitum
- Water (e.g. ad libitum): tap water, sulphur acidified to a pH value of approximately 2,8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk, approx. 10 % of the total body surface
- Type of wrap if used: gauze-dressing with non-irritating tape, fixed with additional dressing in suitable manner.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h
- Washing (if done): tap water

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): n/a (undiluted)
- Constant volume or concentration used: yes (single dose)
Duration of exposure:
24 hours
Doses:
Single dose of 2000 mg/kg body weight to each anima!.
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: clinical observation several times on day of dosing (at least once during first 30 minutes and with special attention given during the first 4 hours post-dose). Symptoms were recorded as soon as noticed. Thereafter, daily observations for clinical signs until end of observation period. All abnormalities were recorded. Animals were weighed on day 1 (prior to application of dose) and on day 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed:
-- In case of gross pathological changes, tissues were preserved for a possible histopathological evaluation.
-- The treated areas of skin were examined daily for signs of primary skin irritation. Signs of erythema and oedema were assessed using the scoring system laid down in OECD Guideline 404, adopted 24th April 2002.

Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: mortality 0/10 Limit test according to OECD 402.
Mortality:
No mortality observed. All animals survived until the end of the observation period of 14 days.
Clinical signs:
No signs of systemic toxicity were observed.
The nasal discharge observed 1 day post-dose in one female animal is not considered to be related to the test item, but to the administration
procedure and the possible stress induced.
No signs of skin irritation were observed.
Body weight:
A slight weight loss was recorded for 1 of 5 female animals during the first week, but all of the female animals showed weight gain during the
second week, The effects on weight development might be secondary to the dressing, and toxicological relevance of this finding cannot clearly be concluded.
The male animals showed weight gain during the first and the second week of the observation.
Gross pathology:
With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal.
Other findings:
No skin irritation was observed at the males and females.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
The LD50-value for acute dermal toxicity of the test substance Ethyltriglycol methacrylate is > 2000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study according to OECD guideline 402 (adopted 24th Feb, 1987), EU Method B.3 (adopted 30 May 2008), 5 male and 5 female young adult WISTAR Crl: WI(Han) rats were dermally exposed to Ethyltriglycol methacrylate (98.95%) for 24 hours unter a semiocclusive dressing to approx. 10% of body surface area at doses of 2000 mg/kg bw. Animals then were observed for 14 days.

No animal died. No signs of skin irritation were observed. No clinical signs of systemic toxicity were observed. A slight weight loss was recorded for 1 of 5 female animals during the first week, but all of the female animals showed weight gain during the second week,

The male animals showed weight gain during the first and the second week of the observation. No macroscopic substance related pathologic organ findings were noted during necropsy.

Dermal LD50

Males > 2000  mg/kg bw

Females > 2000  mg/kg bw

Combined > 2000  mg/kg bw

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
One relevant, reliable (Klimisch score = 1) and adequate study is available for a structutal analog substance is available (Ethyltriglycol methacrylate).

Additional information

Reliable (RL1), relevant and adequate data are available for the acute oral toxicity of BDGMA and for the dermal toxicity of the closely read-across substance Ethyltriglycol methacrylate.

 

Acute oral toxicity

In an acute oral toxicity study according to OECD guideline 401, groups of fasted Sprague Dawley rats (5 males + 5 females) were given a single oral dose of undiluted BDGMA according to supplier's information: purity of 98.97 % at a single dose of 2000 mg/kg and observed for 14 days.

No death occurred. Hypoactivity and piloerection were observed in all animals on day 1. Recovery was complete in all animals on day 2, The body weight gain of the treated animals was similar to that of historical control animals. Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Oral LD50 (rat) =  > 2000 mg/kg bw

 

Acute inhalative toxicity

A study on acute inhalation toxicity is unjustified in accordance to REACH regulation Annex VIII, column 2 due to exposure considerations as well as in accordance to REACH regulation Annex XI due to scientific considerations. The substance has a low vapour pressure. The use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. Furthermore, systemic toxicity relevant to humans did not appear in acute by oral or dermal exposure. Considering the exposure probability and the available information on the intrinsic toxic activity of the substance, an inhalative systemic toxicity risk to humans is unlikely and therefore, the conduct of an inhalative toxicity study is not scientifically necessary. Thus, also animal welfare is respected according to REACH intentions.

 

Acute dermal toxicity

The acute dermal LD50 of the related read-across substance Ethyltriglycol methacrylate is reported to be >2000 mg/kg bw in rat. Based on the absence of acute oral toxicity and limited dermal absorption, dermal toxicity is not expected.

 

Based on the available information, the acute toxicity of BDGMA is low for oral and dermal routes of administration in rat and rabbits. There are no relevant data gaps in acute toxicity. Even though there is no information on acute inhalative toxicity, there is no reason to believe that the acute toxicity is higher for this route of exposure. Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.


Justification for selection of acute toxicity – oral endpoint
Guideline study OECD 401, GLP

Justification for selection of acute toxicity – inhalation endpoint
Inhalation is no relevant route of exposure and testing by inhalation is not appropriate. Exposure of humans via inhalation is unlikely taking into account the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for selection of acute toxicity – dermal endpoint
Guideline study OECD 402, GLP, read across

Justification for classification or non-classification

Based on the available data, BDGMA does not need to be classified for acute toxicity according to regulation (EC) 1272/2008 or the former European directive on classification and labelling 67/548/EEC. Thus, no labelling is required.