Tetradecyl methacrylate

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, only four test animals.

Justification for type of information:

Read across from the dodecyl methacrylate category member donor substance.
REPORTING FORMAT FOR THE CATEGORY APPROACH
see attached category document
RE_501_C12-C22 Long Chain Alkyl Methacrylates
This is a category (C12-C22 Long Chain Alkyl Methacrylates) with clear trends in the physicochemical properties of its members, related to molecular weight, molecular size and hydrophilicity.
For this endpoint, the common primary metabolic pathway of the category members (i.e. common functional groups and rapid metabolism by ester cleavage leading to the common metabolite Methacrylic acid (MAA)) is considered as most relevant aspect of the category approach. Qualitatively, this aspect can be categorized as “(Bio) transformation to common compound(s)”, whereas MAA is understood as toxicological relevant metabolite for local and systemic effects.
The variable part of the category approach is the alcoholic moiety of the parent ester and the alcohol metabolite, respectively, with its impact on physico-chemical properties and subsequent properties as mentioned in chapter 2.2. The short chain alkyl methacrylates are hydrolyzed between 4.4 to 27.2 min DT50 showing a positive correlation between chain length of the alcohol moiety and DT50. (-> “Variation among the category members”). The clearance from liver blood flow i.e. first pass clearance is higher than 99.5% for those esters. For the long chain methacrylates of this category the extension of this trends is anticipated due to clear physicochemical trends and chemical similarity within the group of all alkyl methacrylates. Thus, clearance by hydrolysis is in general given, although not exact quantifiable. However, due to the significantly reduced solubility a relatively small amount of these esters is bioavailable and subsequently in the system ready to be metabolized by carboxyl esterases. The total available burden for the body by the esters is decreasing with increasing chain length of the alcohol part of the molecule. Thus, scenario 3/5 according to RAAF is considered as most relevant for this endpoint; see chapter 1.1.4 for relevant assessment elements. The category approach is conducted with a high level of confidence.
This assessment is in line with that of Gelbke et al. (2017) for the short chain alkyl methacrylates: “The basic assumption for repeated dose toxicity is that due to the relatively short half-life of the parent ester within the body that systemic effects after oral and inhalation exposure are mainly driven by the products of ester hydrolysis, namely MAA and the corresponding alcohols. Local effects after inhalation are determined by local release of MAA, generally to the olfactory epithelium leading to cytotoxicity due to intracellular acidity. This corresponds to scenario 3. The uncertainty associated with inter- and extrapolation of NOAELs for systemic effects after oral and inhalation exposure and local effects after inhalation is low according to the scheme of Blackburn and Stuard (2014)”.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1970

Materials and methods

Principles of method if other than guideline:

Method: no data

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dodecyl methacrylate

EC Number:

205-570-6

EC Name:

Dodecyl methacrylate

Cas Number:

142-90-5

Molecular formula:

C16H30O2

IUPAC Name:

dodecyl methacrylate

Test material form:

liquid

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Duration of treatment / exposure:

4 weeks

Frequency of treatment:

20 x 6 h/d; 5 d/w

Doses / concentrations

Remarks:

Doses / Concentrations:
saturated atmosphere
Basis:

Control animals:

no

Results and discussion

Effect levels

Dose descriptor:

conc. level: saturated atmosphere

Sex:

male/female

Basis for effect level:

other: not specified

Remarks on result:

not measured/tested

Remarks:

Read across from 2-Propenoic acid, 2-methyl, dodecylester (CAS: 142-90-5) (contains 25 % C-14-ester); (CAS: 2549-53-3). Effect level not specified.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

No toxic signs: autopsy, organs normal

Applicant's summary and conclusion

Conclusions:

Read across from n-Dodecyl methacrylate CAS: 142-90-5:
After repeated inhalative screening exposure (20 x 6 h/d; 5 d/w) to 2 female and 2 male rats there were no toxic signs, autopsy and organs normal.

Executive summary:

Read across from n-Dodecyl methacrylate CAS: 142-90-5:

After repeated inhalative screening exposure (20 x 6 h/d; 5 d/w) to 2 female and 2 male rats there were no toxic signs, autopsy and organs normal.