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Description of key information

The acute toxicity of hexadecyl methacrylate ester can be considered as very low as the acute toxicity of the structural analogue substance dodecyl methacrylate by the oral route was determined to be (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). This experimentally observed result is supported by a dermal toxicity study with structural analogue dodecyl pentadecyl methacrylate where a LD50: > 5000 mg/kg, dermal, rabbit was observed. The inhalation route is not of relevance due to the very low  vapour pressure (0.0064 hPa at 25 °C) of the structural analogue substance dodecyl methacrylate.

Key value for chemical safety assessment

Acute toxicity: via oral route

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 with structural analogue 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 – C20) 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 tetradecyl 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 a dermal toxicity study with structural analogue dodecyl pentadecyl methacrylate where a LD50: > 5000 mg/kg, dermal, rabbit was observed (Rohm & Haas, 1975).

Additional information

There are no studies with hexadecyl methacrylate available. Therefore read across approach was made with the structurally analogue substances dodecyl methacrylate, isodecyl methacrylate and dodecyl pentadecyl methacrylate.

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 – C20).

 

Acute inhalative toxicity

There is no acute inhalation study available on hexadecyl methacrylate and long chain alkyl methacrylate esters (C12 - C20).

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 dodecyl methacrylate 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. This experimentally observed result is supported by a dermal toxicity study with structural analogue dodecyl pentadecyl methacrylate where a LD50: > 5000 mg/kg, dermal, rabbit was observed (Rohm & Haas, 1975).

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
There is no study with hexadecyl methacrylate available. No single key study has been selected: instead, all available studies have been used in a weight-of-evidence approach.
Read-across:
The test with structural analogue substance dodecyl methacrylate 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
There is no study with Hexadecyl methacrylate available. 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 hexadecyl 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, hexadecyl 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.