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Directorate-General for Health and Food Safety
Opinion on the results of the Risk Assessment of 2-Propenoic acid (ACRYLIC ACID) - CAS N°: 79-10-7 - EINECS N°: 201-177-9 - Report version : Draft, 05.01.2001 carried out in the framework of Council Regulation (EEC) 793/93 on the evaluation and control of the risks of existing substances1. Opinion expressed at the 24th CSTEE plenary meeting, Brussels, 12 June 2001
In the context of Regulation 793/93 (Existing Substances Regulation), and on the basis of the examination of the Risk Assessment Report, the CSTEE is invited to examine the following issues:
1. Does the CSTEE agree with the conclusions of the Risk Assessment Report
2. If the CSTEE disagrees with such conclusions, the CSTEE is invited to elaborate on the reasons for this divergence of opinion.
Introduction
Acrylic acid is an important intermediate for the polymer industry and is produced at 810 000 tonnes/year within Europe, 20 000 tonnes/year are imported. Acrylic acid is chiefly processed directly into a polyacrylate or polymerised via the intermediate stage of an acrylate ester. Acrylic acid is also used as an ingredient and occurs as residual monomer in consumer products such as adhesives, paints, binding agents and printing inks.
GENERAL COMMENTS
Environment
The environmental part of the RAR is of good quality. The CSTEE supports conclusions i) and ii) for the aquatic environment.
The CSTEE also agrees with the conclusion of no risk for sediments and for bioaccumulation and secondary poisoning.
However, the conclusions of no risk for the atmospheric and soil compartments are not well supported enough by the available information.
Acrylic acid shows specific toxicity on algae and therefore the toxicity on plants should be investigated, including exposures through air and atmospheric deposition. Conclusion i) for the atmosphere should be stated.
Similarly, the risk assessment for the soil is conducted using the equilibrium partitioning method. This method is not acceptable in this particular case. Conclusion i) should be considered and specific toxicity data on terrestrial organisms should be requested.
Human Health
The health part of the document is of good quality. The CSTEE agrees with the general conclusion that there is a need for limiting the risks of acrylic acid concerning acute and chronic respiratory tract irritation and systemic effects from inhalation exposure in working areas involving manufacture of adhesives and use of adhesives, and in skilled trades using adhesives.
SPECIFIC COMMENTS
Environment
Emissions
The major point sources are due to wet polymerisation, but there are huge differences in the site specific information on releases. Clocalwater varies between 0.004 and 10 000 m g/L, which must reflect more than different dilution situations. These differences could have been discussed in the report.
Exposure assessment
Due to the physical-chemical properties of acrylic acid and its emission patterns, the aquatic environment is the most likely to be exposed, even if volatility may occur to some extent.
Acrylic acid is readily biodegradable, therefore concentrations at regional level are not supposed to be relevant. Nevertheless, the high production volume, may allow to produce high concentrations at local level in production/processing and use sites.
Regional and local (general and site-specific) PECs are properly calculated. Nevertheless it must be highlighted that experimental data are not available for aquatic and terrestrial compartments. It is surprising that there are no measured data on environmental concentrations available for a compound which is produced at more than 800 000 tonnes/y in the EU. This leaves the assessor with only predicted exposure data, which is not a satisfactory situation.
Effects assessment
Aquatic environment
Effects assessment on the aquatic environment is based on a large enough number of reliable toxicity data on several organisms, including some long-term figures. Algae are the most sensitive organisms, while toxicity on fish and invertebrates is relatively low. PNECs for water and treatment plants are properly calculated.
Terrestrial environment
Acrylic acid showed a specific toxicity on algae. No information on terrestrial plants is available and therefore the CSTEE considers that this toxicity should be investigated, using both air and soil exposures.
Regarding the soil compartment, the information only covers soil micro-organisms, and the equilibrium partitioning method is applied. However, in this particular case the method extrapolates the toxicity observed to aquatic unicellular algae to terrestrial plants. The large physiological and exposure route (algae surface vs. plant roots) differences do not support this extrapolation.
Risk characterisation
In the aquatic environment, PEC/PNEC values substantially higher than 1 have been calculated for several processing and use scenarios. Therefore the CSTEE supports conclusions i) and ii).
The CSTEE also agrees with the conclusion of no risk for sediments and for bioaccumulation.
For the terrestrial environment, the RAR presents conclusion ii) for the atmosphere, when in reality the report considers that there is no information for assessing these risks.
In the soil compartment, the PEC/PNEC is very close to 1 (0.8) and therefore there is not margin for covering approximations due to extrapolation from algae to terrestrial plants. Toxicity data on terrestrial plants must be requested.
Human Health
Exposure assessment
Occupational
Acrylic acid is primarily used as a chemical intermediate that is further processed to acrylic esters, homopolymers and copolymers. Some of the processed products may contain residual monomer (less than 900 ppm). Occupational exposures via inhalation and the dermal route may occur during production and further processing in the large-scale chemical industry. This involves production and further processing as a chemical intermediate and manufacture of adhesives. Occupational exposure may also occur in the further processing industries, outside the chemical industry. These exposures involve manufacture of adhesives, use of adhesives in the further processing industry and decomposition of photoresistant materials during the production of integrated circuits. In the skilled trade sector exposure to acrylic acid may occur during use of adhesives and gas flame removal of paints. In addition to the exposure from adhesives, both occupational and consumer exposure may come from unreacted acrylic acid in surface coatings (110 000 tonnes/a) and paper coatings (23 000 tonnes/a). Thus, the residue of the monomer in such coatings is very important.
Consumers
Products containing acrylic acid are used as adhesive or glue and in adhesive substances on the basis of solvents. Furthermore, acrylic acid in sealing compounds is also used by consumers. Inhalation exposure may occur for instance during UV-hardening of adhesives. Dermal exposure to the monomer may occur when using sanitary towels, pantyliners or nappy pants where homopolymerisates of acrylic acid are used as superabsorbents. The exposure to a potentially dermal sensitising impurity in a residual monomer in such instances is expected to be very low.
Indirect
Exposure to humans via the environment may occur through food, drinking water and air due to releases from point sources.
Effects assessment
Acrylic acid is a reactive chemical that in concentrated form causes severe local corrosion after dermal contact and severe irritation in the respiratory tract. In 90-day inhalation studies in rats and mice results in degenerative changes in the respiratory tract, mostly in the olfactory epithelium, with mice being more sensitive than rats. Cytotoxic changes were seen at the lowest inhalation concentration, 5 ppm (approx. 15 m g/l) in especially female mice, establishing this as a LOAEC. There were very few indications of systemic toxicity in both rats and mice, a NOAEC for systemic toxicity was established at 5 ppm based on reduced body weight gain in mice. Repeated gavage administration of higher doses of acrylic acid to rats resulted in mortality, ulceration of the stomach and degeneration/necrosis of kidney tubules. Corresponding doses administered through the drinking water did not reveal the serious effects seen after gavage administration.
Computational fluid dynamics and physiologically-based toxicokinetics dosimetry indicated that the olfactory epithelium of the human nasal cavity is exposed to 2-3 fold lower tissue concentrations of acrylic acid than the olfactory epithelium of the rodent nasal cavity. Acrylic acid is rapidly taken up via the dermal route in rats, however, much of the applied amount volatilises. Dermal uptake is pH-dependent with lower uptake at pH 7.4 compared to pH 6.
Commercial acrylic acid is a strong sensitiser, whereas distilled acrylic acid is not. The sensitising effect of the commercial product is presumably due to diacryloxypropionic acid. There is no information available on the potential of acrylic acid to produce respiratory sensitisation.
Acrylic acid does not cause mutations in the Salmonella test, but increases the mutation frequency in the mouse lymphoma cell gene mutation assay and chromosomal aberrations in CHO cells. The effects were concentration-dependent and could not be related to severe cytotoxicity. Acrylic acid did not cause in vitro unscheduled DNA synthesis. A test for sex-linked recessive lethal mutations in Drosophila melanogaster was negative. Two in vivo bone marrow chromosomal aberration assays with rats were negative after drinking water exposure to acrylic acid. Also a dominant lethal assay with mice was negative after gavage administration of acrylic acid. Thus, acrylic acid does not fulfil criteria for classification as a mutagen.
A drinking water carcinogenicity study with rats conducted according to appropriate standards did not give evidence of carcinogenic effects. The highest dose of about 88 mg/kg bw/day led to a reduced water consumption without any other effects. Therefore, the MTD was not completely reached. However, application of higher doses may have resulted in further reduced water intake, which could have influenced the health of the animals severely. This study should be regarded as valid with the restriction mentioned. Two studies with mice and dermal application gave no evidence of local or systemic carcinogenic effects.
As acrylic acid does not have an in vivo mutagenic potential in vitro or the overall assessment in the RAR "There is no evidence that acrylic acid administered orally to rats or applied dermally to mice is carcinogenic" is supported.
There is no inhalation carcinogenicity study. Due to the irritative properties of acrylic acid, a local tumour formation due to irritation and stimulation of cell proliferation might be possible. This hazard can be avoided by keeping the concentrations below the threshold above which irritation in the nasal epithelium is induced (see chapter 4.1.2.6). The level of this threshold is still under scientific debate, because it is not clear if the results obtained with rodents (LOAEC 5 ppm mouse, 90 day study) can be extrapolated directly to humans.
No effects on fertility were seen in a 2-generation reproduction toxicity study where acrylic acid was administered in drinking water to rats. A NOAEL for general toxicity (reduced body weight gain) of 53 mg/kg bw/day was established for the F1-generation. There was no prenatal developmental toxicity observed in rats or rabbits after inhalation. Signs of postnatal developmental toxicity (reduced body weight gain) were seen in the pups, but at dose levels that led to reduced food intake and weight gain in the dams. Thus, acrylic acid is not a reproductive/developmental toxicant.
Risk characterisation
Workers
The RAR documents shift average acrylic acid air levels of 7.5-37.5 mg/m3 during certain activities of manufacture and use of adhesives without local exhaust ventilation. These exposures result in Margin of Safety (MOS) values of 0.4-2 with respect to repeated dose toxicity (irritant effects in the upper respiratory tract). Although these MOS values do not take into account that the dosimetry of acrylic acid in the upper airways may be different in humans compared to mice, the CSTEE agrees with the conclusion of the RAR that these values are considered to be of concern (conclusion iii). The CSTEE also supports the conclusion iii) for systemic effects after inhalation exposure.
Consumers
The CSTEE agrees to the conclusion ii) of the RAR.
Indirect exposure
The CSTEE agress to the conclusion ii) of the RAR.
----------------------------------------
1 Regulation 793/93 provides a systematic framework for the evaluation of the risks to human health and the environment of those substances if they are produced or imported into the Community in volumes above 10 tonnes per year. The methods for carrying out an in-depth Risk Assessment at Community level are laid down in Commission Regulation (EC) 1488/94, which is supported by a technical guidance document.
Terms of reference
In the context of Regulation 793/93 (Existing Substances Regulation), and on the basis of the examination of the Risk Assessment Report, the CSTEE is invited to examine the following issues:
1. Does the CSTEE agree with the conclusions of the Risk Assessment Report
2. If the CSTEE disagrees with such conclusions, the CSTEE is invited to elaborate on the reasons for this divergence of opinion.
Introduction
Acrylic acid is an important intermediate for the polymer industry and is produced at 810 000 tonnes/year within Europe, 20 000 tonnes/year are imported. Acrylic acid is chiefly processed directly into a polyacrylate or polymerised via the intermediate stage of an acrylate ester. Acrylic acid is also used as an ingredient and occurs as residual monomer in consumer products such as adhesives, paints, binding agents and printing inks.
GENERAL COMMENTS
Environment
The environmental part of the RAR is of good quality. The CSTEE supports conclusions i) and ii) for the aquatic environment.
The CSTEE also agrees with the conclusion of no risk for sediments and for bioaccumulation and secondary poisoning.
However, the conclusions of no risk for the atmospheric and soil compartments are not well supported enough by the available information.
Acrylic acid shows specific toxicity on algae and therefore the toxicity on plants should be investigated, including exposures through air and atmospheric deposition. Conclusion i) for the atmosphere should be stated.
Similarly, the risk assessment for the soil is conducted using the equilibrium partitioning method. This method is not acceptable in this particular case. Conclusion i) should be considered and specific toxicity data on terrestrial organisms should be requested.
Human Health
The health part of the document is of good quality. The CSTEE agrees with the general conclusion that there is a need for limiting the risks of acrylic acid concerning acute and chronic respiratory tract irritation and systemic effects from inhalation exposure in working areas involving manufacture of adhesives and use of adhesives, and in skilled trades using adhesives.
SPECIFIC COMMENTS
Environment
Emissions
The major point sources are due to wet polymerisation, but there are huge differences in the site specific information on releases. Clocalwater varies between 0.004 and 10 000 m g/L, which must reflect more than different dilution situations. These differences could have been discussed in the report.
Exposure assessment
Due to the physical-chemical properties of acrylic acid and its emission patterns, the aquatic environment is the most likely to be exposed, even if volatility may occur to some extent.
Acrylic acid is readily biodegradable, therefore concentrations at regional level are not supposed to be relevant. Nevertheless, the high production volume, may allow to produce high concentrations at local level in production/processing and use sites.
Regional and local (general and site-specific) PECs are properly calculated. Nevertheless it must be highlighted that experimental data are not available for aquatic and terrestrial compartments. It is surprising that there are no measured data on environmental concentrations available for a compound which is produced at more than 800 000 tonnes/y in the EU. This leaves the assessor with only predicted exposure data, which is not a satisfactory situation.
Effects assessment
Aquatic environment
Effects assessment on the aquatic environment is based on a large enough number of reliable toxicity data on several organisms, including some long-term figures. Algae are the most sensitive organisms, while toxicity on fish and invertebrates is relatively low. PNECs for water and treatment plants are properly calculated.
Terrestrial environment
Acrylic acid showed a specific toxicity on algae. No information on terrestrial plants is available and therefore the CSTEE considers that this toxicity should be investigated, using both air and soil exposures.
Regarding the soil compartment, the information only covers soil micro-organisms, and the equilibrium partitioning method is applied. However, in this particular case the method extrapolates the toxicity observed to aquatic unicellular algae to terrestrial plants. The large physiological and exposure route (algae surface vs. plant roots) differences do not support this extrapolation.
Risk characterisation
In the aquatic environment, PEC/PNEC values substantially higher than 1 have been calculated for several processing and use scenarios. Therefore the CSTEE supports conclusions i) and ii).
The CSTEE also agrees with the conclusion of no risk for sediments and for bioaccumulation.
For the terrestrial environment, the RAR presents conclusion ii) for the atmosphere, when in reality the report considers that there is no information for assessing these risks.
In the soil compartment, the PEC/PNEC is very close to 1 (0.8) and therefore there is not margin for covering approximations due to extrapolation from algae to terrestrial plants. Toxicity data on terrestrial plants must be requested.
Human Health
Exposure assessment
Occupational
Acrylic acid is primarily used as a chemical intermediate that is further processed to acrylic esters, homopolymers and copolymers. Some of the processed products may contain residual monomer (less than 900 ppm). Occupational exposures via inhalation and the dermal route may occur during production and further processing in the large-scale chemical industry. This involves production and further processing as a chemical intermediate and manufacture of adhesives. Occupational exposure may also occur in the further processing industries, outside the chemical industry. These exposures involve manufacture of adhesives, use of adhesives in the further processing industry and decomposition of photoresistant materials during the production of integrated circuits. In the skilled trade sector exposure to acrylic acid may occur during use of adhesives and gas flame removal of paints. In addition to the exposure from adhesives, both occupational and consumer exposure may come from unreacted acrylic acid in surface coatings (110 000 tonnes/a) and paper coatings (23 000 tonnes/a). Thus, the residue of the monomer in such coatings is very important.
Consumers
Products containing acrylic acid are used as adhesive or glue and in adhesive substances on the basis of solvents. Furthermore, acrylic acid in sealing compounds is also used by consumers. Inhalation exposure may occur for instance during UV-hardening of adhesives. Dermal exposure to the monomer may occur when using sanitary towels, pantyliners or nappy pants where homopolymerisates of acrylic acid are used as superabsorbents. The exposure to a potentially dermal sensitising impurity in a residual monomer in such instances is expected to be very low.
Indirect
Exposure to humans via the environment may occur through food, drinking water and air due to releases from point sources.
Effects assessment
Acrylic acid is a reactive chemical that in concentrated form causes severe local corrosion after dermal contact and severe irritation in the respiratory tract. In 90-day inhalation studies in rats and mice results in degenerative changes in the respiratory tract, mostly in the olfactory epithelium, with mice being more sensitive than rats. Cytotoxic changes were seen at the lowest inhalation concentration, 5 ppm (approx. 15 m g/l) in especially female mice, establishing this as a LOAEC. There were very few indications of systemic toxicity in both rats and mice, a NOAEC for systemic toxicity was established at 5 ppm based on reduced body weight gain in mice. Repeated gavage administration of higher doses of acrylic acid to rats resulted in mortality, ulceration of the stomach and degeneration/necrosis of kidney tubules. Corresponding doses administered through the drinking water did not reveal the serious effects seen after gavage administration.
Computational fluid dynamics and physiologically-based toxicokinetics dosimetry indicated that the olfactory epithelium of the human nasal cavity is exposed to 2-3 fold lower tissue concentrations of acrylic acid than the olfactory epithelium of the rodent nasal cavity. Acrylic acid is rapidly taken up via the dermal route in rats, however, much of the applied amount volatilises. Dermal uptake is pH-dependent with lower uptake at pH 7.4 compared to pH 6.
Commercial acrylic acid is a strong sensitiser, whereas distilled acrylic acid is not. The sensitising effect of the commercial product is presumably due to diacryloxypropionic acid. There is no information available on the potential of acrylic acid to produce respiratory sensitisation.
Acrylic acid does not cause mutations in the Salmonella test, but increases the mutation frequency in the mouse lymphoma cell gene mutation assay and chromosomal aberrations in CHO cells. The effects were concentration-dependent and could not be related to severe cytotoxicity. Acrylic acid did not cause in vitro unscheduled DNA synthesis. A test for sex-linked recessive lethal mutations in Drosophila melanogaster was negative. Two in vivo bone marrow chromosomal aberration assays with rats were negative after drinking water exposure to acrylic acid. Also a dominant lethal assay with mice was negative after gavage administration of acrylic acid. Thus, acrylic acid does not fulfil criteria for classification as a mutagen.
A drinking water carcinogenicity study with rats conducted according to appropriate standards did not give evidence of carcinogenic effects. The highest dose of about 88 mg/kg bw/day led to a reduced water consumption without any other effects. Therefore, the MTD was not completely reached. However, application of higher doses may have resulted in further reduced water intake, which could have influenced the health of the animals severely. This study should be regarded as valid with the restriction mentioned. Two studies with mice and dermal application gave no evidence of local or systemic carcinogenic effects.
As acrylic acid does not have an in vivo mutagenic potential in vitro or the overall assessment in the RAR "There is no evidence that acrylic acid administered orally to rats or applied dermally to mice is carcinogenic" is supported.
There is no inhalation carcinogenicity study. Due to the irritative properties of acrylic acid, a local tumour formation due to irritation and stimulation of cell proliferation might be possible. This hazard can be avoided by keeping the concentrations below the threshold above which irritation in the nasal epithelium is induced (see chapter 4.1.2.6). The level of this threshold is still under scientific debate, because it is not clear if the results obtained with rodents (LOAEC 5 ppm mouse, 90 day study) can be extrapolated directly to humans.
No effects on fertility were seen in a 2-generation reproduction toxicity study where acrylic acid was administered in drinking water to rats. A NOAEL for general toxicity (reduced body weight gain) of 53 mg/kg bw/day was established for the F1-generation. There was no prenatal developmental toxicity observed in rats or rabbits after inhalation. Signs of postnatal developmental toxicity (reduced body weight gain) were seen in the pups, but at dose levels that led to reduced food intake and weight gain in the dams. Thus, acrylic acid is not a reproductive/developmental toxicant.
Risk characterisation
Workers
The RAR documents shift average acrylic acid air levels of 7.5-37.5 mg/m3 during certain activities of manufacture and use of adhesives without local exhaust ventilation. These exposures result in Margin of Safety (MOS) values of 0.4-2 with respect to repeated dose toxicity (irritant effects in the upper respiratory tract). Although these MOS values do not take into account that the dosimetry of acrylic acid in the upper airways may be different in humans compared to mice, the CSTEE agrees with the conclusion of the RAR that these values are considered to be of concern (conclusion iii). The CSTEE also supports the conclusion iii) for systemic effects after inhalation exposure.
Consumers
The CSTEE agrees to the conclusion ii) of the RAR.
Indirect exposure
The CSTEE agress to the conclusion ii) of the RAR.
----------------------------------------
1 Regulation 793/93 provides a systematic framework for the evaluation of the risks to human health and the environment of those substances if they are produced or imported into the Community in volumes above 10 tonnes per year. The methods for carrying out an in-depth Risk Assessment at Community level are laid down in Commission Regulation (EC) 1488/94, which is supported by a technical guidance document.
