Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
carcinogenicity
Route of original study:
By inhalation
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: EU Scientific Committee on Occupational Exposure Limits (SCOEL), 1993
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
carcinogenicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
other:
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
other:

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General considerations

In general, the DNEL derivation for the substance was performed under consideration of the recommendations of ECHA REACH Guidance (2010) and ECETOC (2010). In addition and with regard to the most sensitive endpoint of respiratory tract irritation, the DNEL for local effects after long term inhalation exposure was derived according to principles of the EU Scientific Committee on Occupational Exposure Limits (SCOEL, 1993), while for local effects after long term dermal exposure an induction-specific DNEL was derived for skin sensitization according to Guidance on information requirements and chemical safety assessment, Chapter R.8 (ECHA, May 2008) based on the EC3 value from an LLNA study (BAMM 2006). In view of the data used for evaluation, the "quality of whole database factors" is considered to amount to a value of 1.

Acute/short-term inhalation exposure- systemic effects

Butyl acrylate is of low toxicity after short-term inhalation. The substance is classified for acute inhalation (vapour) as acute Category 4 according to Regulation (EC) No 1272/2008. However, the acute systemic toxicity is covered by the long term inhalation DNEL for local effects which by far is the most sensitive endpoint with regards to the respiratory irritation. Therefore, no DNEL for acute/short term inhalational systemic efefcts was derived.

Long-term inhalation exposure - systemic effects

Butyl acrylate showed no evidence of carcinogenicity or any systemically relevant effect in a 2-year vapour inhalation study, leading to a very high bioavailability, in Sprague-Dawley rats up to the highest tested dose (135 ppm = 0.773 mg/L). In addition, dose-level selection for long-term studies was limited due to the irritative potential leading to severe local effects on the upper respiratory tract. Therefore, no DNEL for long term inhalational systemic efefcts was derived.

Long-term inhalation exposure - local effects

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 1993 the EU Scientific Committee on Occupational Exposure Limits (SCOEL) recommended an 8 hour OEL (TWA) of 2 ppm (11 mg/m3) for n-butyl acrylate. This recommended OEL is taken as DNEL as 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 requirements and chemical safety assessment, Chapter R.8: Characterisation of dose (concentration)-response for human health (May 2008).

The SCOEL decision is based on the most actual data, the 2 year inhalation study (Reininghaus et al. 1991). The critical effect of n-butyl acrylate is atrophy of the olfactory epithelium. In a well conducted study, rats were exposed to 15, 45 and 135 ppm (80, 240 and 720 mg/m3), 6h/d, 5d/w for 2 years (Reininghaus et al, 1991). Dose-related changes were observed in the olfactory epithelium and cornea, with minimal effects in a few animals at the lowest dose, and almost all animals being affected at the high dose. Changes in the eyes were non-significant at the low and medium doses. During a 6-month recovery period, the altered olfactory epithelium was replaced by respiratory epithelium. No treatment-related tumours were reported. The study of Reininghaus et al (1991), establishing a LOAEL of 15 ppm (80 mg/m3) for atrophy of the olfactory epithelium in rats, was considered to be the best available basis for proposing occupational exposure limits. SCOEL considered an uncertainty factor of 5 appropriate to allow for the absence of a NOAEL and of reliable human data. Taking into account the preferred value approach, the recommended 8-hour TWA is 2 ppm (11 mg/m3). A STEL (15 min) of 10 ppm (53 mg/m3) was proposed to limit peaks of exposure which could result in irritation.

Also the German MAK commission evaluated butyl acrylate with a comparable conclusion. They also identified the local irritation of the olfactory epithelium of the nasal mucous membranes as the most critical effect, occurring even in the lowest concentration tested (15 ppm). According to MAK the database is, however, suitable for estimating the no observed adverse effect concentration from the dose-response relationship according to the benchmark concept. The most sensitive relevant end point is seen as the loss of olfactory and ciliated cells and hyperplasia of the reverse cells after exposure for 24 months. For this effect a benchmark concentration of 2.8 ppm has been established for female animals and 2.7 ppm for males. Taking into consideration the reversibility of these findings in some cases the MAK value for n-butyl acrylate was set at 2 ppm. MAK also assumed that due to the particular nasal anatomy and respiratory physiology of the rat (DeSesso 1993), a higher tissue dose is attained in the olfactory epithelium of the rat than in man. It was therefore expected that man does not react more sensitively than the rat, and the burden in man under the same exposure conditions is more likely to be overestimated.

Acute/short-term inhalation exposure - local effects

Butyl acrylate is of medium local toxicity after short-term inhalation. The substance is classified for respiratory irritation after acute inhalation exposure according to Regulation (EC) No 1272/2008 (CLP). In addition, based on local effects on skin, eyes and respiratory tract the substance is allocated to the moderate hazard band (H315, H319, H335). But the acute local toxicity is covered by the long term inhalation DNEL for local effects, which is by far the most sensitive endpoint with regards to the respiratory irritation. Therefore, no DNEL for acute/short term inhalational local effects was derived.

Acute/short-term and long-term dermal exposure - local effects

The substance is irritating to the skin and causes skin sensitization in experimental animals For sensitisation the EC3 value was reported to be 11.2 % w/v (2800 μg/cm2) (BAMM 2006), indicative of a sensitiser of weak potency (ECETOC 2003). For these local effects, a qualitative assessment is conducted.

Therefore the use of gloves and the use of stringent risk management measures as outlined in ECHA guidance document Part E: Risk Characterization (Table E. 3-1) is required in order to prevent any skin contact with the test substance and thus the occurrence of skin sensitization and skin irritation.

The use of gloves and of stringent risk management measures will also protect the worker from any systemic dermal effects, short-term and long-term.

- ECETOC (2003). Contact Sensitization: classification according to potency. Technical Report No. 87, April 2003.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
carcinogenicity
Route of original study:
By inhalation
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

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:
no hazard identified

Additional information - General Population

Butyl acrylate per se is not intended for consumer use. However, end-use consumer products may contain trace amounts of acrylic acid and its esters due to the polymerization process as residuals. As a consequence, consumer exposure to acrylate monomers including butyl acrylate can be considered at least as very low or as negligible, if any. But even in the case of very low exposure to tiny amounts of butyl acrylate it was shown that even long term inhalation exposure with its high bioavailability did not led to carcinogenicity or systemic toxicity up to the highest biologically feasible concentration (135 ppm = 0.773 mg/L). In addition, butyl acrylate was not carcinogenic, when applied to the skin of mice throughout their lifetime at 1% corresponding to about 8 mg/kg bw. Therefore, no DNELs were derived.

Reference:

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