methyl acrylate; methyl propenoate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

18 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

other: 2004 EU Scientific Committee on Occupational Exposure Limits (SCOEL) value

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

Methyl acrylate is a chemical intermediate, manufactured and processed within closed systems. The primary routes of industrial exposure to methyl acrylate are skin contact and inhalation. In an industrial setting, ingestion is not an anticipated route of exposure.

Long-tern exposure systemic DNELs were not calculated because of the lack of long-term systemic effects. Dose-level selection for long-term studies was limited by severity of local effects on the upper respiratory tract.

DNEL derivation:

The EU Scientific Committee on Occupational Exposure Limits  (SCOEL) makes recommendations to the Commission on 'health-based' OELs. An OEL of this type may be established in those cases where a review of the total available scientific database leads to the conclusion that it is possible to identify a clear threshold dose below which exposure to the chemical in question is not expected to lead to adverse effects. The European Commission uses the scientific advice from SCOEL to make proposals for occupational exposure limits. Limits based solely on scientific considerations are considered as adaptations to technical progress, and are incorporated in proposals for Commission directives within the framework of the chemical agents directive and are indicative.

In September 2004 the EU Scientific Committee on Occupational Exposure Limits (SCOEL) recommended an 8 hour OEL (TWA) of 5 ppm (18 mg/m³) for methyl acrylate. This reommended OEL is taken as DNEL, it is based on actual and well documented  toxicological information and evaluation of health effects, in which the approach how it is derived is scientifically justified and is therefore in accordance with ECHA Guidance on information requirments and chemical safety assessment, Chapter R.8: Characterisation of dose (concentration)-response for human health (May 2008).

There are no human data available which are adequate for proposing occupational exposure limits.

The study of Reininghaus et al. (1991), establishing a LOAEL of 15 ppm (54 mg/m³), for slight irritation of the olfactory epithelium in rats, was considered to be the best available basis for proposing occupational exposure limits.

In this well-conducted 2 year study Sprague-Dawley rats (86 rats per sex and group) developed no systemic effects at concentrations of 15, 45 and 135 ppm Methylacrylate (54, 161 or 483 mg/m³). In the cornea a dose-related increase in neovascularization and parenchymal cloudiness was observed in male and female animals. However, little importance can be attached to this finding because it is a result of anatomical and geriatric features of the rat which are not found in man. The rat eye is spherical and the cornea highly domed so that external factors have more effect on the rat than on the human eye. The lacrimal glands of some strains including the Sprague-Dawley rat, are often subject to age-related changes. This is also to be seen in the author's own historical data for the Wistar rat. The changes lead to inadequate lacrimation which means that the cornea of such animals is no longer adequately protected. Any additional adverse external influences, such as the irritation caused by methyl acrylate, can then result in (dose dependent) corneal changes. Furthermore, the neovascularization of the cornea in rats exposed to methyl acrylate is known to be a reversible non-specific reaction to chronic irritation. Thus the alterations in the lacrimal glands and cornea which developed in rats under the conditions described above are not to be expected in man. Corneal damage has not been reported in workers in factories producing methyl acrylate (DFG 1993). The critical effect was irritation of the nasal mucosa. Dose-related changes occurred in the nasal mucosa at the level of the dorsal lamella of the second endoturbinate. At the lowest concentration tested (15 ppm, 54 mg/m³) slight atrophy of the neurogenic part of the olfactory epithelium was observed in a few male rats. At 45 and 135 ppm, almost all exposed rats developed a partial loss of the columnar cell layer, with an accompanying stratified reserve-cell hyperplasia . No treatment-related changes were detected in the posterior nasal cavity, which is mainly lined with olfactory epithelium. No irritative changes were observed in the larynx, trachea or lungs of the exposed rats. The LOAEL of this study for basal-cell hyperplasia (critical effect) is 15 ppm with a very steep concentration-response-curve at higher concentrations (Reininghaus et al., 1991). Calculation of a benchmark dose (BenchMark dose Software from US EPA, Version 1.3.2, dichotomous logistic model with 0.95 confidence level) gave a BMDL of 14 ppm. In contrast to methylacrylate, the concentration-response-curve for butylacrylate was flat, resulting in a BMDL of 6 ppm, which is in accordance with the 8-h TWA of 2 ppm.

In view of the mild nature of this localized lesion, observed in a well-conducted study and

the very steep concentration-response-curve beyond 15 ppm, the Scientific Committee of Occupational Exposure Limits considered an uncertainty factor of 2 appropriate to allow for the absence of a NOAEL and of human data. This is in accordance with the calculated BMDL of 14 ppm. Taking into account the preferred value approach, the recommended 8-hour TWA is 5 ppm (18 mg/m3). A short term exposure limit (STEL) (15 mins) of 10 ppm (36 mg/m³⁾ was proposed to limit peaks of exposure which could result in irritation.

• Recommendation from the Scientfic Committee on Occupational Exposure Limits for Methylacrylate, SCOEL/SUM/46, September 2004

In addition, a qualitative risk assessment approach was conducted for dermal local acute and long term exposure based upon skin sensitization as a hazard in accordance with the Guidance on information requirements and chemical safety assessment, Chapter R.8 (ECHA, Nov 2012). A medium hazard conclusion was based on the EC3 value of 19.6% w/v (4900µg/cm²), indicative of a sensitizer of weak potency.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

Since end-use consumer products contain only trace levels of acrylic acid and esters (as a result of polymerization), consumer exposure to acrylate monomers is likely to be low (SRI, 2001).

• SRI, 2001 . CEH Marketing Research Report, Acrylic Acid and Esters, 606 .4000A, Chemical Economics Handbook -SRI International .