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Administrative data

Description of key information

The acute toxicity of dodecyl methacrylate ester can be considered as very low by the oral (LD50: > 5000 mg/kg, oral, rat, OECD 401, GLP, Klimisch score: 1) and

dermal route (LD50: > 3000 mg/kg, Structurally related substance Isodecyl methacrylate, dermal, rabbit, Klimisch score: 2). Peer reviewed handbook data of Dodecyl methacrylate LD50: > 3000 mg/kg, dermal, rabbit (Nemec JW, Kirch LS, 1978) supports this result. The inhalation route is not of relevance due to the very low vapour pressure (0.0064 hPa at 25 °C) of the substance.

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:
25-10-1988 - 08-11-1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
OECD 401, GLP.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Supplier: Evonik Röhm GmbH, D-64293 Darmstadt, Germany
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability of test article dilution: stable for at least 2 hr
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Wistar rats (strain: BOR: WISW (SPF TNO)), F. Winkelmann GmbH & Co KG, Borchen, Germany
- Age at study initiation: 9 weeks
- Weight at study initiation: Males: 202 - 205 ± 7-9 g; Females: 186 - 187 ± 5-7g
- Fasting period before study: overnight before test begin
- Housing: Groups of 5 in Makrolon cages
- Diet: ad libitum, Ssniff R food
- Water: ad libitum drinking water
- Acclimation period: One week under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hr light/ 12 hr dark period.
Route of administration:
oral: gavage
Vehicle:
water
Doses:
5000 mg/kg b.w. and a gavage volume of 10 mL/kg b.w.
No. of animals per sex per dose:
5 males, 5 females per dose group
Control animals:
yes
Details on study design:
- Test article preparation: immediately prior to dosing
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: After administration of the test substance the rats are weighted again and held in single macrolon cages. Clinical examination was made twice a day during the length of the acute period of the intoxication, thereafter once a day.
- Necropsy of survivors performed: all animals were necropsied.
- Other examinations performed: clinical signs and symptoms, body weight, mortality, macroscopic findings
The tissues of all rats are weighted: lung, livers, kidneys, spleens, adrenals and testes; all pathological changes were recorded.
Statistics:
The t-test was the adequate statistical value for comparison the results between the experimental and control groups.
Preliminary study:
The limit dose of 5000 mg/kg b.w. were applied to the rats as a range finding dose.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
Mortality was neigther observed in the experimental group nor in the controls during the observation period of 14 days.
Clinical signs:
The clinical appearance and behavior of the male and female rats did not differ from the controls for the whole experimental period, except of oily
fouled skin in the rectum region of all experimental rats at the first day, and rough hair for the first two days after treatment .
Body weight:
For the male and also female rats there was no difference in the mean body weight between the experimental and control groups during the
whole study.
Gross pathology:
At necropsy substance-related signs of toxicity were not clearly obvious in comparison to the controls. The only observations were similar
incidences of red and white foci on the lung surface of the experimental and control rats. But in 2/5 male and 1/5 female rats slightly swollen liver
margins were observed for the experimental group only.
The results of the mean tissue weights show no differences between the experimental and control groups.

Results:

Mortality (dead/total 5)

Time range of deaths (days)

Male

Female

Combined

Control

0

 0

 0

 14

5000

 0

 0

14

Interpretation of results:
GHS criteria not met
Remarks:
GHS no category.
Conclusions:
According to the test result: LD50(14days): > 5000 mg/kg bw the test substance Dodecylmethacrylate has to be classified as practically nontoxic in rats in respect of its acute oral toxicity.
Executive summary:

In an acute oral toxicity study according to OECD guidline 401 (Limit test) with GLP, groups of fasted male and female SPF Wistar rats were given a single oral dose of Dodecylmethacrylate (purity: 97%) at a dose of 5000 mg/kg bw and observed for 14 days.

 

Oral LD50 Combined = > 5000 mg/kg bw

   

Dodecylmethacrylate is oral practically nontoxic in SPF Wistar rats (OECD GHS no category) based on this LD50 test in males and females.

Based on the available data, Dodecyl methacrylate does not need to be classified for acute toxicity according to regulation (EC) 1272/2008.

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:
5 000 mg/kg bw
Quality of whole database:
There is one relevant, adequate and reliable study for Dodecyl methacrylate available (FHG, 1988) (Klimisch score = 1) The test was performed in accordance with generally accepted scientific standards and described in sufficient detail. Guideline study OECD 401, GLP.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
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 low vapour pressure and the low possibility of exposure to aerosols, particles or droplets of an inhalable size.
Furthermore no reliable data are available on long-chain methacrylate esters (C12 – C22) for the inhalation route. However, data are available on the structural analogues substances: methyl-, ethyl- and n-butyl methacrylate. The respective LC50 values are in a range between 5000 and 11000 ppm indicating low inhalation toxicity.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 000 mg/kg bw
Quality of whole database:
In a dermal acute toxicity study on Isodecyl methacrylate (structurally related substance of Dodecyl methacrylate) with Albino Rabbits an
LD50 > 3000 mg/kg was determined. Reliable study according to generally accepted scientific standards and decribed in sufficient detail. This
experimentally observed result is supported by the peer reviewed handbook data of Dodecyl methacrylate LD50: > 3000 mg/kg, dermal, rabbit
(Nemec JW, Kirch LS, 1978).

Additional information

Reliable (RL1), relevant and adequate data are available for the acute oral toxicity of dodecyl methacrylate and for the dermal toxicity of the closely related read-across substance Isodecyl 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 Dodecyl methacrylate according to supplier's information: purity of 97 % at a single dose of 5000 mg/kg and observed for 14 days.

No death occurred. The body weight gain of the treated animals was similar to that of control animals. At necropsy substance-related signs of toxicity were not clearly obvious in comparison to the controls. The only observations were similar incidences of red and white foci on the lung surface of the experimental and control rats. But in 2/5 male and 1/5 female rats slightly swollen liver margins were observed for the experimental group only.

Oral LD50 (rat) =  > 5000 mg/kg bw

Furthermore, acute oral toxicity studies with LD50 values above 5000 mg/kg indicate a very low toxic potential of the long-chain alkyl methacrylate esters (C12 – C22).

 

Acute inhalative toxicity

There is no acute inhalation study available on dodecyl methacrylate and long chain alkyl methacrylate esters (C12 - C22).

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 very low vapour pressure (0.0064 hPa at 25 °C). 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. Therefore, the inhalation route is not of relevance.

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 scientifically not meaningful. Thus, animal welfare is respected according to REACH intentions.

 

Acute dermal toxicity

There is no reliable acute dermal study available on dodecyl methacrylate. However, the acute dermal LD50 of the closely related read-across substance Isodecyl methacrylate is reported to be >3000 mg/kg bw in rabbits. Peer reviewed handbook data of dodecyl methacrylate, a value of LD50: > 3000 mg/kg, dermal, rabbit (Nemec JW, Kirch LS, 1978) supports this result.

There are only few data on dermal toxicity testing of the long chain alkyl methacrylate esters in rabbits which are of limited reliability. With regard to the low acute oral toxicity and the characteristics of skin penetration and metabolism in the skin, the acute dermal toxicity can be considered as low.

This skin absorption study indicates that the total amount of the ester dodecyl methacrylate that was absorbed during the time of exposure was 0.7 % (rat epidermis) and 0.26 % (rat whole skin) over 24 hours, respectively.

Hence, bearing in mind the already low acute oral toxicity, toxic effects via the dermal route are unlikely.

In conclusion, there are sufficient data available for the toxicological assessment of the long-chain alkyl methacrylate esters. Hence, for the sake of animal welfare it is not proposed to conduct further studies.

 

Based on the available information, the acute toxicity of dodecyl methacrylate is low for oral and dermal routes of administration in rat and rabbits. There are no data gaps in acute toxicity. Even though there is no information on acute inhalative toxicity, there are no indications 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
The test was performed in accordance with generally accepted scientific standards and described in sufficient detail. Reliable guideline study according to OECD 401 without restrictions performed with GLP.

Justification for selection of acute toxicity – dermal endpoint
No single key study has been selected: instead, all available studies have been used in a weight-of-evidence approach.
Read-across:
In a dermal acute toxicity study on Isodecyl methacrylate (structurally related substance of Dodecyl methacrylate) with Albino Rabbits an LD50 > 3000 mg/kg was determined. Reliable study according to generally accepted scientific standards and described in sufficient detail.

Justification for classification or non-classification

Based on the available data, Dodecyl methacrylate 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.

For read across purposes according to ECHA's RAAF (2017), this study is applicable with a high level of confidence.