Survey and safety assessment of Chemical substances in artificial nails and nail hardeners
6 Safety assessment
- 6.1 Safety assessment of substances in nail hardeners
- 6.2 Safety assessment of substances in artificial nails
Safety assessments were performed on formaldehyde found in nail hardeners, and 2-hydroxyethyl acrylate, 2-hydroxypropyl acrylate, 2-hydroxypropyl dimethacrylate and ethylene dimethacrylate found in artificial nail products. The toxicological effects of the substances are described, including the ability of the substances to induce allergy. This effect is considered to be the most critical effect due to the amount of literature describing contact allergy after use of nail hardeners and/or artificial nails.
When data were available, a NO(A)EL[2] for the critical effect of the substances has been established. The NO(A)EL value is applied in Chapter 7 on exposure scenarios and risk assessments of the products.
6.1 Safety assessment of substances in nail hardeners
6.1.1 Formaldehyde
Identification
Formaldehyde is a colourless, flammable, reactive and readily polymerising gas at normal temperature and pressure. It is a gas with a pungent, irritating odour (2).
Formaldehyde is a normal metabolite in mammalian organisms. It can be generated by the metabolism of certain xenobiotics or endogenous compounds, such as amino acids (3).
| Chemical name | Formaldehyde |
| Synonyms | Formic aldehyde, methanal, methylene oxide, methylaldehyde, oxymethylene, oxomethane |
| CAS-No. | 50-00-0 |
| EINECS No. | 200-001-8 |
| Molecular formula | CH2O |
| Molecular structure |  |
| Legislation: Classification in accordance with the list of hazardous substances (4) Cosmetics (1) |
T; R23/24/25: Toxic by inhalation, in contact with skin and if swallowed. C; R34: Causes burns. CARC3; R40: Limited evidence of a carcinogenic effect R43: May cause sensitization by skin contact. A maximum amount of 5% in nail hardeners allowed |
Physical-Chemical properties
| Physical state | Gas |
| Molecular weight (g/mol) | 30.03 |
| Melting point | -92° C (5) |
| Boiling point | -19.5° C (5) |
| Vapour pressure | 3890 mm Hg at 25° C (5) |
| Octanol/water partition coefficient (log Kow) | 0.35 (5) |
Acute toxicity
Systemic effects
The toxic effect observed after exposure of formaldehyde (by inhalation) may be, depending on dose, weakness, headache, abdominal pain, anaesthesia, anxiety, burning sensation in the nose and throat, thirst, clammy skin, central nervous system depression, cyanosis, diarrhoea, dizziness, irritation and necrosis of mucous membranes and gastrointestinal tract, vomiting, nausea, coma, and shock (6).
Ingestion of aqueous solutions of formaldehyde may cause renal injury and lead to an increase in formate levels in the urine (6).
Local effects
Skin irritation and sensitisation
Formaldehyde is irritating to eyes, skin and mucosal membranes (3). With standard patch test protocols, formaldehyde concentrations of 2% and higher is observed to produce skin irritation in non-sensitised individuals (7).
No significant pulmonary function decrements have been observed in adults with or without asthma after three hours of exposure to 0.5 to 3 ppm (0.6 - 3.6 mg/m³) formaldehyde. Most studies show no effect on lung function after formaldehyde exposure (3,8).
Induction of dermal sensitisation to formaldehyde has been observed after dermal exposure. A threshold for induction has not been clearly established, but it is estimated to be less than 5 % aqueous solution (3). Different studies has classified formaldehyde as a moderate to strong sensitizer (9,10,11).
In an guinea pig maximization test sensitisation was observed in 100% of the animals at a formaldehyde concentration of 2% (7).
An LLNA (Local Lymph Node Assay) test has been performed on formaldehyde showing that formaldehyde has a potential to induce sensitisation. Induction of sensitisation was observed at a concentration of 0.96% formaldehyde (12). In another LLNA test a formaldehyde concentration of 0.4 % induced sensitisation (9).
Over the last 30 years, a large number of human patch tests have been performed with aqueous formaldehyde solutions in concentrations up to 2% (7). Allergic reactions to formaldehyde concentrations of 1% has been observed in patients with skin problems (7).
In a serial dilution test 8/35 formaldehyde-sensitised subjects developed allergy to the lowest concentration tested (0.1%) (7). In another test, a few positive reactions were observed at concentrations below 0.1% formaldehyde. The following response frequencies were observed: 9/20 at 0.5%, 3/20 at 0.1%, 2/20 at 0.05%, and 1/20 at 0.025% (7).
Studies of concentration-response relationships for skin allergic reactions caused by occluded dermal exposures of formaldehyde in formaldehyde-sensitised subjects suggest that a elicitation of sensitisation to formaldehyde concentrations below about 0.025 – 0.05% is rare (7).
In conclusion, LLNA tests has shown that formaldehyde is able to induce sensitisation and indicated that formaldehyde concentrations as low as 0.4 – 0.96% may induce sensitisation in non-sensitised subjects. For formaldehyde-sensitised subjects, a large number of human patch tests have been performed. It is concluded that formaldehyde concentrations below 0.025 – 0.05% rarely elicitate sensitisation.
Furthermore, it has been reported that with standard patch test protocols, formaldehyde concentrations of 2% and higher may produce skin irritation in non-sensitised individuals demonstrating that concentrations that evoke a skin irritation response is similar to those evoking allergic skin responses.
Toxicity from repeated or prolonged exposure
Repeated formaldehyde exposure causes toxic effects only in the tissues of direct contact after inhalation, oral or dermal exposure characterized by local tissue destruction and subsequent repair of the damage. The typical locations of lesions in experimental animals are the nose after inhalation, the stomach after oral administration and the skin after dermal application. The nature of the lesions depends on the inherent abilities of the tissues involved to respond to the noxious event and on the local concentration of the substance (3).
In a 2 years chronic feeding study in rats a NOAEL of 15 mg/kg/day was obtained. The NOAEL was based on development of lesions of the gastric mucosa and histopathological changes in the kidneys after administration of formaldehyde via the drinking water (13).
An oral RfD[3] of 0.2 mg/kg bw/day is established based on this study on chronic toxicity in rats (13).
Genotoxicity
Formaldehyde is genotoxic in different in vitro systems (14,15,16).
Several in vivo studies are available on the mutagenic potential of formaldehyde. The conclusion of the studies is insufficient and there is conflicting evidence for genotoxic potential of formaldehyde in humans exposed to occupational levels (6).
Carcinogenicity
Formaldehyde is carcinogenic at the site of contact as a consequence of epithelial cell regenerative proliferation resulting from tissue destruction and mutation, based on studies in both animals and humans (14).
A TD50[4] has been reported for rats and mice. The lowest TD50 was found for rats at 1.35 mg/kg bw/day (17). Based on this value, an acceptable dose may be estimated to 2.7 × 10-6 mg/kg bw/day[5]. After exposure to this dose, there is a risk of cancer in 1 out of 1 million exposed persons. This level of risk is generally accepted.
Reproductive toxicity
There is no evidence that formaldehyde may induce teratogenicity or may affect reproduction by inhalation exposure (6).
Critical effect
The induction and elicitation of dermal sensitisation are considered as critical effect from dermal formaldehyde exposure. A threshold for induction has not been clearly established for humans. However, a concentration level of 0.4 – 0.96% formaldehyde has been established as the lower concentration for induction of skin sensitisation in LLNA tests. Furthermore, a large number of human patch tests have been performed. From these it is concluded that formaldehyde concentrations below 0.025 – 0.05% rarely elicitate sensitisation in formaldehyde-sensitised subject.
Therefore, a concentration of 0.01% formaldehyde may be considered as a safe concentration including both formaldehyde-sensitised subjects and the induction of non-sensitised subjects. A safety factor of 100 is included for the data from LLNA tests for extrapolation of data from animals to humans and including of particularly sensitive human individuals.
An oral Reference Dose (RfD) of 0.2 mg/kg bw/day is established for formaldehyde based on a NOAEL of 15 mg/kg bw/day in rats administrated formaldehyde by drinking water. The effects were reduced body weight gain and effects in the gastro-intestinal tract.
Formaldehyde has a carcinogenic potential. An acceptable dose for lifetime risk of cancer has been estimated to 2.7 × 10-6 mg/kg bw/day. After exposure to this dose, there is a risk of cancer in 1 out of 1 million exposed persons. This risk level is generally accepted.
Table 6.1 Summary of data for formaldehyde
| Toxicological data (animals) | |
| NOAEL, intake, rat | 15 mg/kg bw/day |
| Acceptable dose - lifetime risk, cancer | 2.7 × 10-6 mg/kg bw/day |
| Oral Reference Dose (RfD) | 0.2 mg/kg bw/day |
6.2 Safety assessment of substances in artificial nails
6.2.1 2-Hydroxyethyl acrylate
Identification
2-Hydroxyethyl acrylate is colourless liquid with a sweet pleasant odour (5).
2-Hydroxyethyl acrylate is included in the positive list of monomers and other starting substances for plastics and coatings intended to come into contact with foodstuffs. While there are no recommendations for a specific migration limit or residual level, the European Commission has suggested a group maximum total daily intake of 0.1 mg/kg body weight acrylates (measured as acrylic acid). (18).
| Chemical name | 2-Hydroxyethyl acrylate |
| Synonyms | Ethylene glycol, monoacrylate, hydroxyethyl acrylate, 2-propenoic acid, 2-hydroxyethyl ester |
| CAS-No. | 818-61-1 |
| EINECS No. | 212-454-9 |
| Molecular formula | C5H8O3 |
| Molecular structure |  |
| Legislation: Classification in accordance with the list of hazardous substances (4) |
T; R24: Toxic in contact with skin C; R34: Causes burns Xi; R36/38: Irritating to eyes and skin R43: May cause sensitisation by skin contact N; R50: Very toxic to aquatic organisms |
Physical-Chemical properties
| Physical state | Liquid |
| Molecular weight (g/mol) | 116.13 |
| Melting point | No information |
| Boiling point | 191° C (19) |
| Vapour pressure | 0.0523 mmHg at 25° C (19) |
| Octanol/water partition coefficient (log Kow) | -0.21 (5) |
Acute toxicity
Systemic effects
Studies on the acute toxicity of 2-hydroxyethyl acrylate indicate oral LD50 values of 540 – 1070 mg/kg bw. Clinical signs (following administration of a 10% aqueous solution) included hypoactivity, rough fur, muscle weakness, gastro-intestinal tract haemorrhage in animals that died. Neat material may have caused chemically burns in the tissues of the mouth, throat, and gastro-intestinal tract (18).
Acute dermal toxicity studies showed LD50 values of 154 (rabbits, undiluted material) and >1000 mg/kg bw (rats, vehicle olive oil). At high concentrations decreased eyelid tone, decreased corneal reflex, loss of righting reflex and muscle coordination were noted (18).
Acute inhalation data indicate that exposures of rats to 333 to 394 ppm (» 1580 - 1870 mg/m³) 2-hydroxyethyl acrylate for 4 or 8 hours caused irritation and were in the threshold area for lethality. Nearly 100% lethality was observed for rats at exposures of 500 ppm (2500 mg/m³) and above (18).
These data indicate that 2-hydroxyethyl acrylate is moderately acute toxic.
Local effects
Skin irritation and sensitisation
2-Hydroxyethyl acrylate is severely irritating to the skin (5,18). Several studies have shown that undiluted 2-hydroxyethyl acrylate is severely irritating to the skin if left in contact with the skin for a sufficient period of time (18). Upon eye contact, 2-hydroxyethyl acrylate may cause severe irritation with irreversible corneal injury (18).
Skin sensitization studies in animals and humans indicate that 2-hydroxyethyl acrylate is a sensitizer and may cross-react with other acrylates in some exposed individuals. 2-Hydroxyethyl acrylate has been found to be a sensitizer in both local Lymph Node Assays (LLNA), Buehler tests and maximization tests in guinea pigs; however some of the studies being of older date (1970 – 1995) (18). Twelve acrylate-sensitised patients were tested with various substances including 2-hydroxyethyl acrylate in a patch test. Ten out of twelve patients had a positive reaction to 2-hydroxyethyl acrylate when tested at a concentration of 0.1% (20). In another human patch test with acrylate-sensitised subjects 8% of the test persons reacted positive to 2-hydroxyethyl acrylate in a 0.1% concentration (21).
Based on these studies 2-hydroxyethyl acrylate is evaluated to have a moderate potential to elicitate sensitisation in acrylate-sensitised subjects.
Toxicity from repeated or prolonged exposure
Repeated exposures to vapours of 2-hydroxyethyl acrylate (0, 5, 10, 25 ppm » 0, 24, 48, 119 mg/m³) to rats via inhalation (7 hr/day, 5 days/week for four weeks) caused severe nasal irritation, resulting in death due to respiratory failure at higher concentrations. The LOAEC was estimated to 5 ppm (25 mg/m³) for 2-hydroxyethyl acrylate based on corneal irritation (18). In another study the effects observed following 18 months exposure of laboratory rats to 5 ppm of 2-hydroxyethyl acrylate were related to irritation of the respiratory tract, without significant evidence of systemic toxicity (18).
Dietary studies with rats and dogs have shown that 2-hydroxyethyl acrylate has a low toxicity after repeated dosing via this route. No effects were observed in the highest tested dose up to 131 mg/kg bw/day. A NOAEL of 131 mg/kg bw/day was established in dogs fed up to 131 mg/kg bw in their diet (18).
Genotoxicity
2-Hydroxyethyl acrylate was not mutagenic to S. typhimurium (bacterial reverse mutation assay) in vitro with or without metabolic activation but was positive with metabolic activation when tested with two E. coli strains. No evidence of chromosomal damage was seen in an 18-month inhalation study. Four rats pr. sex pr. group were killed after 12-months exposure and the bone marrow cells examined for chromosomal damage. No effects were observed (18). Overall, 2-hydroxyethyl acrylate did not show evidence of mutagenic potential in vivo by the inhalation route of exposure (18).
Carcinogenicity
No evidence of a carcinogenic effect was observed in a chronic toxicity/oncogenicity study conducted by the inhalation route of exposure (18).
Reproductive toxicity
Histopathological examination of the reproductive organs of rats from an 18-month inhalation study revealed an increase in age-related lesion (fibrinoid degeneration in the vascular channels of the testes) and uterine inflammation (without any other associated histopathological effects). Neither effects were considered treatment-related or adverse to reproduction (18).
Dietary administration of 2-hydroxyethyl acrylate to rats or dogs did not result in treatment-related effects on testicular weight or histopathology of the testes or uterus (18).
Critical effect
The critical effect of 2-hydroxyethyl acrylate is its potential to induce and elicitate irritation and sensitisation. No lower dose has been established for sensitisation, but elicitation of allergy was observed at a concentration of 0.1%. Based on the available studies on 2-hydroxyethyl acrylate it is evaluated that the substance has a moderate potential to induce sensitisation.
Table 6.2 Summary of data for 2-hydroxethyl acrylate
| Toxicological data (animals) | |
| NOEL, (mg/kg bw), oral, dog | 131 mg/kg bw/day |
6.2.2 2-Hydroxypropyl acrylate
Identification
2-Hydroxypropyl acrylate (HPA) is a clear to light yellow liquid with a sweet odour (22).
Only limited data has been identified on 2-hydroxypropyl acrylate. However, data was found on hydroxypropyl acrylate (CAS no. 25584-83-2). A typical commercial product of hydroxypropyl acrylate contains approximately 75-80% 2-hydroxypropyl acrylate and 20-25% 1-methyl-2-hydroxyethyl acrylate. Below, data on toxicology for this commercial product is also used to describe the toxicity of 2-hydroxypropyl acrylate.
| Chemical name | 2-hydroxypropyl acrylate |
| Synonyms | 1,2-Propanediol, 1-acrylate, propylene glycol monoacrylate, beta-hydroxypropyl acrylate |
| CAS-No. | 999-61-1 |
| EINECS No. | 213-663-8 |
| Molecular formula | C6H10O3 |
| Molecular structure |  |
| Legislation: Classification in accordance with the list of hazardous substances (4) |
T; R23/24/25: Toxic by inhalation, in contact with skin and if swallowed. C; R34: Causes burns. R43: May cause sensitisation by skin contact |
Physical-Chemical properties
| Physical state | Liquid |
| Molecular weight (g/mol) | 130.14 (22) |
| Melting point | No information |
| Boiling point | 77° C (22) |
| Vapour pressure | 0.174 mmHg at 25° C (19) |
| Octanol/water partition coefficient (log Kow) | 0.35 (19) |
Acute toxicity
Systemic effects
2-Hydroxypropyl acrylate is of moderate to low toxicity after oral exposure. The rat oral LD50 was 250 to 500 mg/kg bw with reports of values as high as 590 to 1300 mg/kg bw. The mouse oral LD50 value was 1060 mg/kg bw (22).
LD50 values in rabbits after topical application range from 170 mg/kg bw to 250 mg/kg bw. The animals that survived developed moderate oedema, moderate to severe necrosis, and local evidence of irritation at the application site (22).
Local effects
Skin irritation and sensitisation
2-Hydroxypropyl acrylate is irritating to the eyes, nasal and respiratory organs (22). Hydroxypropyl acrylate is highly irritating to the skin (23).
Skin sensitization studies in animals and humans indicate that hydroxypropyl acrylate is likely to be a sensitizer and will cross-react with other acrylates in some exposed individuals. 2-Hydroxypropyl acrylate is among the more potent sensitisers in guinea pigs (22). Nine acrylate-sensitised patients were tested with various substances including 2-hydroxypropyl acrylate in a patch test. Seven out of nine patients had a positive reaction to 2-hydroxypropyl acrylate tested in a concentration of 0.1% indicating a sensitisation potential (20).
It is evaluated based on human and animal data that 2-hydroxypropyl acrylate has a moderate potential to elicitate and induce allergy.
Toxicity from repeated or prolonged exposure
Repeated exposure to vapours of hydroxypropyl acrylate (6 hr/day, 5 days/week for 21 or 20 exposures to rats and mice and rabbits and dogs, respectively) did result in severe irritation of the upper respiratory tract, resulting in death due to respiratory failure at higher concentrations and concentration-related local irritation at sub-lethal exposures. The LOAEC, based on irritation, was 5 ppm (27 mg/m³) for hydroxypropyl acrylate. No systemic toxicity was observed (23).
Genotoxicity
2-Hydroxypropyl acrylate was not mutagenic in an in vivo mouse micronucleus study (23).
Hydroxypropyl acrylate was not mutagenic to S. typhimurium (bacterial reverse mutation assay) in vitro with or without metabolic activation but was positive with metabolic activation when tested with two E. coli strains. In mammalian cells in vitro, hydroxypropyl acrylate was negative in a gene mutation assay but had clastogenic activity in cytogenetic and chromosomal aberration assays. In these mammalian cell assays, positive results occurred only at concentrations that resulted in significant cell death. Thus, the positive results are considered equivocal. Hydroxypropyl acrylate was not mutagenic in an in vivo mouse micronucleus study (23).
Overall, hydroxypropyl acrylate is considered not to have mutagenic potential in vivo based on available data.
Carcinogenicity
No data found
Reproductive toxicity
Based on results from animal studies evaluating exposure to hydroxypropyl acrylate and 2-hydroxyethyl acrylate vapours, no reproductive toxicity is anticipated for 2-hydroxypropyl acrylate. Hydroxypropyl acrylate is not selectively toxic to the embryo or foetus and is not teratogenic via inhalation exposure (23).
Critical effect
The critical effect of 2-hydroxypropyl acrylate is its potential to elicitate and induce allergic reactions and to irritate the skin. No clearly threshold dose has been established for this moderate potential for sensitisation effects, but elicitation of allergic reactions was observed at a concentration of 0.1% 2-hydroxypropyl acrylate in humans.
Table 6.3 Summary of data for 2-hydroxpropyll acrylate
| Toxicological data (animals) | |
| LOAEC, (mg/m³), inhalation, rat | 27 mg/m³ » 7 mg/kg bw/day |
6.2.3 2-Hydroxypropyl methacrylate
Identification
2-Hydroxypropyl methacrylate is a dear liquid with a slightly acrylic odour (5).
| Chemical name | 2-hydroxypropyl methacrylate |
| Synonyms | 1,2-Propanediol, 2-methyl, monomethacrylate, Hydroxypropyl methacrylate, Propylene glycol monomethacrylate |
| CAS-No. | 27813-02-1 |
| EINECS No. | 248-666-3 |
| Molecular formula | C7H12O3 |
| Molecular structure |  |
| Legislation: Classification in accordance with the list of hazardous substances (4) |
Not classified |
Physical-Chemical properties
| Physical state | Liquid |
| Molecular weight (g/mol) | 144.18 (5) |
| Melting point | -89° C (19) |
| Boiling point | 87° C (24) |
| Vapour pressure | 0.022 mmHg at 25° C (24) |
| Octanol/water partition coefficient (log Kow) | 0.48 (24) |
Acute toxicity
Systemic effects
2-Hydroxypropyl methacrylate has a low oral acute toxicity. LD50 in rats is 11200 mg/kg bw after oral exposure (19,24).
Local effects
Skin irritation and sensitisation
2-Hydroxypropyl methacrylate vapour is irritating to eyes and respiratory system. The liquid is irritating to eyes (5).
In guinea pigs 2-hydroxypropyl methacrylate had a weak potential to induce sensitisation in a maximisation test (24).
2-Hydroxypropyl methacrylate is observed to elicitate allergic reactions in patch tests. 17.5% of the tested acrylate-sensitised patients were reacting to 2-hydroxypropyl methacrylate in a concentration of 2% (21). In another patch test eleven acrylate-sensitised patients were tested with various substances including 2-hydroxypropyl methacrylate. Six out of eleven patients had a positive reaction to 2-hydroxypropyl methacrylate tested in a concentration of 2% indicating a weak potential for elicitation of allergic reactions (20).
Toxicity from repeated or prolonged exposure
No data found
Genotoxicity
2-Hydroxypropyl methacrylate induced clastogenicity at 0.35 mg/ml with and without activation in an in vitro assay (24). No other studies have been found on the mutagenic effects of 2-hydroxypropyl methacrylate.
Carcinogenicity
No data found
Reproductive toxicity
In a rat study a NOAEL of 1000 mg/kg bw/day was established for reproductive and developmental effects indicating that 2-hydroxypropyl methacrylate has a low potential to cause reproductive toxicity (24).
Critical effect
The critical effects of 2-hydroxypropyl methacrylate are its potential to elicitate and induce allergic reactions. No clearly threshold dose has been established for this effect, but elicitation of allergic reactions was observed at a concentration of 2% 2-hydroxypropyl methacrylate in humans.
A NOAEL was established in a reproductive toxicity study in rats.
Table 6.4 Summary of data for 2-hydroxypropyl methacrylate
| Toxicological data (animals) | |
| NOAEL, (mg/kg bw/day), reprotoxicity, rat | 1000 |
6.2.4 Ethylene dimethacrylate
Identification
Biologically, methacylates resemble acrylates, except for lower reactivity and thus decreased toxicity. This is probably due to steric hindrance by its methyl group (5).
| Chemical name | Ethylene dimethacrylate |
| Synonyms | Ethylene glycol dimethacrylate, ethyldiol metacrylate, glycol dimethacrylate |
| CAS-No. | 97-90-5 |
| EINECS No. | 202-617-2 |
| Molecular formula | C10H14O4 |
| Molecular structure |  |
| Legislation: Classification in accordance with the list of hazardous substances (Gov. order 923 of 2005) (4) |
Xi;R37: Irritating to respiratory system R43: May cause sensitisation by skin contact |
Physical-Chemical properties
| Physical state | Liquid |
| Molecular weight (g/mol) | 198.22 (5) |
| Melting point | -40° C (5) |
| Boiling point | 80.7° C (19) |
| Vapour pressure | 0.188 mmHg at 25° C (19) |
| Octanol/water partition coefficient (log Kow) | 2.2 (5) |
Acute toxicity
Systemic effects
Ethylene dimethacrylate has a low acute toxicity. LD50 orally in mice is 2,000 mg/kg bw, while in rats the value is 3,300 mg/kg bw (19).
Local effects
Skin irritation and sensitisation
Ethylene dimethacrylate is irritating to eyes and respiratory tract (5).
Twenty six acrylate-sensitised patients were tested with various substances including ethylene dimethacrylate in a patch test. Twenty out of twenty six patients had a positive reaction to ethylene dimethacrylate tested in a concentration of 2% indicating a potential for eliciting allergic reactions (20). In another human patch test 13% of the acrylate-sensitised subjects reacted positive to ethylene dimethacrylate in a 2% concentration (21). Based on a Local Lymph Node Assay (LLNA) ethylene dimethacrylate was classified with an extremely weak potency for sensitisation. The concentration inducing sensitisation was 35% ethylene dimethacrylate (25).
Based on these animal and human studies it is evaluated that ethylene dimetacrylate have a weak potential as a sensitiser.
Toxicity from repeated or prolonged exposure
Repeated exposure to ethylene dimethacrylate (6 hr/day, for 13 exposures to rats) in a concentration of 1 mg/m³ produced slightly lethargy. Body weights and urine parameters were unchanged (26).
Carcinogenicity
No data found.
Genotoxicity
Ethylene dimethacrylate was not mutagenic in Ames test (S. typhimurium) with or without activation (26). The substance did induce mutations at the TK gene locus in L5178Y mouse lymphoma cells with metabolic activation in concentrations from 400 to 700 nl/ml. Without metabolic activation, concentrations up to 800 nl/ml caused high cytotoxicity without increasing mutation frequency (5).
Based on these studies the mutagenic potential of ethylene dimethacrylate is not fully verified.
Reproductive toxicity
No data found.
Critical effect
The critical effects of ethylene dimethacrylate are its potential to elicitate and induce allergic reactions. No clearly threshold dose has been established for this effect but elicitation of allergic reactions was observed at a concentration of 2% ethylene dimethacrylate in humans.
No NOAEL for systemic effects were found.
Table 6.5 Summary of data for ethylene dimethacrylate
| Toxicological data (animals) | |
| - | - |
Footnotes
[2] No Observed (Adverse) Effect Level
[3] RfD: Reference Dose; calculated from NOAEL and an safety factor of normally 100
[4] TD50: The lifetime dose rate (mg/kg bw/day) to induce tumours in half of test animals that would have remained tumour free at zero dose.
[5] Acceptable dose: (TD50 x 2) x 10-6
Version 1.0 July 2008, © Danish Environmental Protection Agency