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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
86.4
Modified dose descriptor starting point:
LOAEL
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

Workers - Hazard for the eyes

Additional information - workers

Acrolein is manufactured and used as monomer for polymerization, or as on-site isolated or transported isolated intermediate under strictly controlled conditions. Therefore, hazardous exposure is limited to accidental exposure. Details are given in section 9. “Exposure assessment”.

Acute toxicity

A DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential for high peak exposures. Due to the irritating properties of acrolein to the respiratory tract this exposure route was considered to be relevant for infrequent, accidental inhalative exposures to acrolein. In conclusion, the derived DNEL "Long-term exposure – systemic and local effects inhalation" is considered to be also protective against local effects by short-term exposure.

 

Monitoring of strictly controlled conditions during handling and processing of acrolein revealed that occupational exposure levels of acrolein in ambient air are well below 0.08 mg/m³ in the worst case (during loading and unloading) and thus are well below the national threshold of 0.2 mg/m³ (TRGS 900/TWA/OEL) res. the derived DNEL "Long-term exposure - systemic and local effects inhalation".

 

Irritation/sensitisation

Acrolein is corrosive to eyes and skin. Exposure to skin or eyes may occur only accidentally. As the derived acute DNEL takes already effects on skin and eye into account (see above), separate DNELs irritation skin/eye need not be derived. Due to the applied adequate RMMs it is concluded that workers are not at risk with respect to skin and eye irritation.

Acrolein is not classified for skin sensitisation and a respiratory sensitisation is indicated neither from human experience nor from other sources.

Therefore, no DNEL sensitisation was derived.

 

Mutagenicity/ Carcinogenicity

 “From the results of the mutagenicity studies it is concluded that acrolein has intrinsic genotoxic properties, being positive in gene mutation tests in vitro with bacteria and mammalian cells within a very narrow dose range. Acrolein did not exhibit genotoxic activity in mammals in vivo as appeared from the negative results obtained in a dominant lethal test with mice and a bone marrow chromosome aberration test with rats. The occurrence of genotoxic effects locally at the site of first contact can, however, not be completely excluded.”

 

“Therefore, it is concluded that concern remains for carcinogenic and genotoxic effects locally at the exposure site after long-term exposure by inhalation to non-cytotoxic concentrations.”

“It can be hypothesised that in analogy with other aldehydes such as formaldehyde and possibly acetaldehyde carcinogenic effects will not occur when irritation, as indicator for cytotoxicity, is avoided, but carcinogenic activity at non-cytotoxic exposure levels cannot be fully excluded.”, quotation from EU, 2001.

 

Taking into account that the risk for carcinogenic effects after inhalation may be low at air concentrations where irritation is avoided and the processing is conducted under strictly controlled conditions, the derived DNELlong term inhalation is considered to be sufficient for protection against carcinogenic risks.

 

Repeated dose toxicity:

Oral route

The overall NOAEL for repeated dose toxicity oral route is 0.05 mg/kg bw/day from a chronic study in rats.

No DNEL derived, since the oral route is not relevant to workers.

Inhalation route

For inhalation route the overall LOAEL is 0.9 mg/m3 from a sub-chronic inhalation study in rats, rabbits and hamsters. The DNELlong term systemic inhalationis 0.2 mg/m3. For local long term effects the DNELlong term systemic inhalationis considered to be protective due to the focus on respiratory symptoms in the respected study.

The Executive Management of the Hazardous Substances Committee – (AGS – BauA, Germany) gives the following Statement on Acrylaldehyde in the TRGS 900 (Ger. Technical Rules for Hazardous Substances):

 

The most sensitive endpoint of acrolein effects is local irritation and cytotoxicity in the upper respiratory tract and eye irritation. If local irritation and cytotoxicity are avoided, there should also be no risk of any local genotoxicity, since this effect was only observedin vitroin the cases of pronounced cytotoxicity. The studies by Feron et al. 1978 are taken as the starting point for derivation of a tolerance limit, in which hamsters, rats and rabbits were exposed to acrolein inhalation for a period of 13 weeks, 6 hours a day, 5 days a week. This study is to be preferred because it includes a detailed histopathological examination, in particular of the nose and airways, and was a comparative study in 3 species. On the basis of local effects on nasal mucosa, a NOAEL of 0.9 mg/m³ (0.4 ppm) was determined in hamsters. In view of slight inflammatory changes in the nasal mucosa in only one of 12 animals, this concentration was considered as an LOEL in rats. Since the changes were slight and occurred in only one animal, it can be assumed that the NOAEL is very close to a concentration of 0.9 mg/m³in rats as well. An LOAEL-to-NOAEL extrapolation factor would therefore appear to be unnecessary in this case.

 

Rabbits proved to be less sensitive, with an NOAEL of 3.2 mg/m³.

 

An additional interspecies extrapolation factor is also unnecessary, since within these inhalation studies in which various species has been investigated, the outcomes of these studies indicate that rats and hamsters are the most sensitive species, which is also plausible based on the anatomical relationships (large surface area of respiratory epithelium, obligatory nasal respiration in rats). A chronic study with hamsters conducted by the same working group can be used in analysis of the temporal extrapolation. In the 90-days study, the animals were exposed to 0.9, 3.2 and 11.2 mg/m³ and the 52-weeks study was carried out with a concentration of 9.2 mg/m³. The findings in the nasal epithelium after 52 weeks of inhalation exposure to 9.2 mg/m³ were somewhat more severe (light to moderate inflammation and metaplasia in the anterior nasal segment, neutrophilic infiltration in the mucosa and submucosa, swelling of the submucosa, reduction of number of subepithelial glands, metaplastic stratified epithelium) than after 90 days of exposure to 3.2 mg/m³ (metaplasia and leukocyte infiltration in the anterior nasal segment), but milder than the findings after exposure to 11.2 mg/m³ in the 90-days study (necrotizing inflammation and metaplastic stratified epithelium in the anterior nasal segment, neutrophilic infiltration of the mucosa, focal hyperplasia and metaplasia in the tracheal epithelium, slightly swollen laryngeal epithelium).

 

It can therefore be assumed that chronic exposure does not result in exacerbation of the effects and in lowering of the NOAEL compared to subchronic exposure. Therefore, an additional extrapolation factor for the exposure time is not necessary.

 

Since no specific data are available on intraspecies variability, the standard factor 5 is used (Anon, 1998).

 

Summary of extrapolation steps:

 

Extrapolation steps:

LOAEL -> NOAEL:                                    1

Interspecies extrapolation                         1

Temporal extrapolation                             1

Intraspecies and interspecies variability  1/5

0.9 m³g/m³x 1/5 = 0.18 mg/m³

 

Rounding off accordingly results in a value of 0.2 mg/m³ or 0.09 ppm

 

Taken into account on the human lid closure reflex NOAEL (Weber-Tschopp, 1977) of 0.4 mg/m³(or 0.17 ppm), a momentary value of 0.4 mg/m³ or 0.2 ppm can be derived for acrolein (Factor 2).

 

Since the EU-Risk Assessment has been published in the year 2003 and the derivation of the German Occupational Exposure Limit by the BAUA has been revised in the year 2007 the available data base did not change substantially. In fact, the carried out assumption based on a sub chronic LOAEC of 0.9 mg/m3 for local effects on the most sensitive species (rats) have been confirmed by the newly find sub chronic NOAEC of 0.458 mg/m3 within the study of DORMAN et al.(2008). In which a NOAEL of 0.2 ppm (0,458 mg/m3) has been derivated. The documented irritation effects at a concentration > 0.2 ppm, correspond to the findings in earlier studies (FERRON et al.,1978). Therefore, the study of DORMAN et al. (2008) confirms the results and assumption of the German TRGS completely. The tested dosages (NOAEL 0.458, mg/m3(0.2 ppm) , LOAEL1.374 mg/m³ (0.6 ppm) lies below and above the LOAEL of the FERRON study (1978) with 0.9; 3.2 und 11.2 mg/m3.

 

Finally, it can be assumed, that during the derivation of the German OEL by the BAUA all relevant facts (including the HBORV) have been taken into account. Since the study of DORMAN et al. (2008) verifies this derivation, no further reflections are necessary. 

In conclusion, the DNEL for the inhalative route is 0.2 mg/m3.

Dermal route

A LOAEL of 7 mg/kg bw/day based on local and systemic findings was assessed from a 21-day dermal study in rabbits.

-Applied assessment factors:

Interspecies:

- Allometric scaling: 2.4 (for rabbit)

- Remaining differences: 1 (cf ECETOC Guidance on Assessment Factors to Derive DNELs (Draft, CEFIC, March, 2010)

Intraspecies (worker): 3 (cf ECETOC Guidance on Assessment Factors to Derive DNELs (Draft, CEFIC, March, 2010)

Exposure duration: Subacute to chronic: 6

Dose-response curve: 2 (for use of a LOAEL instead of a NOAEL)

Quality of whole database: 1

Total: 86.4

Thus, the DNELlong term systemic dermal of 0.081mg/kg bw/day is also considered to be protective for local symptoms. 

 

Reproductive toxicity:

In the reproductive toxicity studies performed with acrolein in rats no treatment related developmental effects or effects on reproduction parameters were observed in the animals up to and including the respective high dose groups. Thus, DNELs for reproductive toxicity were not calculated.

It is concluded that there is no risk for any potential reproductive toxic effect of acrolein.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Only workers in the chemical industry could be potentially exposed to acroelin by accident from industrial sources. The general population might be exposed from natural sources as acrolein is formed, e.g. in thermal processing of food in the household. However, a possible exposure from natural sources is outside the scope of teh REACH regulation and therfore not covered within this risk assessment. Therefore, DNELs for general population need not to be derived.