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Substitution of Cobalt Driers and Methyl Ethyl Ketoxime

9 Environmental and health assessment

The environmental and health assessment of driers as well as anti-skinning agents will be done on groups of substances rather than single substances as specific information is very sparse. In some cases it has even been impossible to obtain information about the exact identity of the substances from manufacturers. In general, environmental and health information about specific substances is limited.

The groups of substances to be evaluated are selected based on the screening and on the results of the technical testing of the identified alternatives. Constituents of the most promising alternative driers and anti-skinning agents are included in the environmental and health assessment in order to assess the overall improvements of the environment and health profiles of air-drying products in connection with a substitution.

If substances are excluded on the basis of the screening, there is no need for a more thorough assessment. However, some exceptions are made: The existing driers (cobalt driers) and anti-skinning agents (methyl ethyl ketoxime and hydroquinone) are all included in the environment and health assessment in order to compare their environment and health effects with the alternatives.

The petroleum distillates are selected for evaluation as they are present in most of the drier products and the anti-skinning agents in considerable amounts and they are often classified due to health and environmental effects.

The groups to be evaluated are:

As far as specific information about the tested substances is available this information is included in the evaluation.

9.1 Driers

The driers to be evaluated are the existing cobalt driers, and the alternatives manganese and vanadium driers.

9.1.1 Cobalt driers

Cobalt paint driers are typically either

• Cobalt naphthenate (CAS-no. 61789-51-3) or
• Cobalt 2-ethyl hexanoate (CAS-no. 136-52-7).

Cobalt compounds in general are also included in the assessment of the ecotoxic and toxic effects of cobalt driers because the information on the specific cobalt driers is limited.

9.1.1.1 Cobalt naphthenate
Cobalt(II) naphthenate (CAS-no. 61789-51-3) is a cobalt salt of naphthenic acid, which is a mixture of cycloalkanic acids. Cobalt naphtenate is insoluble in water, but soluble in alcohol, ether and oils, /28/

A study has shown that the absorption of cobalt naphthenate after oral ingestion is limited in rats – up to 73% of the dose was excreted in the faeces. Similarly, experiments have shown that the skin absorption of cobalt napthenate in rats is minimal, /28/.

The acute toxicity of cobalt naphthenate is very low (oral LD₅₀ of 3900 mg/kg in rats), which may be because of the low solubility causing a low absorption, /28/.

Aerosols of cobalt naphthenate are irritating to the eyes and the respiratory tract. Repeated or prolonged contact may develop lung or skin allergy, /22/28/.

IARC (International Agency for Research on Cancer) classifies cobalt and cobalt compounds as a group 2B substance i.e. the substance is possibly carcinogenic to humans. A single Polish study has shown development of tumours in rabbits and mice following cobalt naphthenate exposure, but the study was found to be inadequate by IARC, /28/. IARC concludes that there is inadequate evidence for the carcinogenicity of cobalt naphthenate, /23/.

No data on ecotoxicity was found for this specific substance.

9.1.1.2 Cobalt 2-ethylhexanoate
The information about cobalt 2-ethylhexanoate is very limited. Most of the information refers to cobalt compounds in general.

Cobalt 2-ethylhexanoate may cause irritation of the skin. Prolonged or repeated contact may cause dermatitis of the allergic type, /22/. Furthermore, cobalt 2-ethylhexanoate is found to damage kidneys, /29/.

No data on environmental fate or toxicity was found for this specific substance.

9.1.1.3 Cobalt compounds
Cobalt is, as Vitamin B₁₂ (cyanocobalamin), an essential trace element in humans and animals. Vitamin B₁₂ acts as a coenzyme in many enzymatic reactions. Cobalt exists in the valence states –1, 0, +1, +2, +3, +4, and +5, where 0, +2 and +3 are the most common, and cobalt +2 the most stable. The two typical cobalt paint driers cobalt 2-ethyl hexanoate and cobalt naphthenate are both cobalt (II) compounds, /30/.

Results indicate that only a portion (probably less than 50%) of ingested cobalt will be absorbed. Insoluble cobalt compounds are in general absorbed much less than soluble cobalt compounds, /28/. Inhaled cobalt particles are deposited in the lungs and subsequently absorbed. Dermal absorption of cobalt compounds depends greatly on whether the skin is intact or damaged. Studies show that absorption through intact skin is very small (below 1%), while absorption through abraded skin can be as high as 80% three hours after exposure (measured for cobalt chloride). Absorbed cobalt is transported throughout the body in the blood, with largest levels found in liver, followed by the kidney, /30/.

Oral LD₅₀ values for different cobalt compounds (cobalt chloride, cobalt oxide, cobalt sulphate, cobalt acetate, cobalt bromide) indicate that cobalt compounds are toxic by ingestion, /30/.

The primary targets following acute exposures to cobalt are in humans the respiratory system (inhalation exposure), the thymus (oral exposure), and the immunological system (dermal exposure). The effects of chronic occupational exposure to cobalt compounds on the respiratory system are well documented, and include effects like respiratory irritation, wheezing, asthma, and pneumonia. Furthermore, effects on the nervous system, including memory loss, nerve deafness, and a decreased visual activity, have been reported for occupational exposure to cobalt. Ingestion of cobalt can cause nausea, vomiting, and diarrhea, but has also resulted in e.g. respiratory, cardiovascular, muscoskeletal, haematological, and body weight effects, /29/30/.

Irritation of the skin is a common result of dermal exposure to cobalt in humans. This has been verified in a large number of studies. Contact allergy has been reported, as well as allergic dermatitis following oral exposure to cobalt. The studies indicate that cobalt is a sensitizer, /30/.

Soluble cobalt salts are shown to interfere adversely with cell division, to introduce chromosome aberrations in plants and to be mutagenic to some cultured animal cells. However, in other test systems cobalt compounds are non-mutagenic, co-mutagenic or anti-mutagenic. The conclusion is that cobalt salts are slightly genotoxic, /31/.

Jensen and Tüchsen, /31/, concluded that there seems to be sufficient evidence that cobalt, and soluble as well as insoluble cobalt compounds are carcinogens in animal experiments, and that data for evaluation of human cancer risk is insufficient, but indicates a carcinogenic potential in humans. The material available indicates that it is the cobalt metal itself, which is the problem with regard to cancer. The results of several studies suggest a relationship between occupational cobalt exposure and excess lung cancer mortality, /29/30/. On the basis of the available material IARC classifies cobalt and cobalt compounds as a group 2B substance i.e. the substance is possibly carcinogenic to humans, /23/. Cobalt compounds in general are also adapted on the Danish list of carcinogenic substances, /32/.

Inhalation and oral studies in male animals have demonstrated adverse effects on reproductive organs, /30/.

Cobalt released into water may absorb to particles in the water or sediment, or remain in the water in ionic form. Cobalt deposited on soil is often strongly attached to soil particles, and will not travel very far into the ground. The specific fate of cobalt will depend on different chemical factors; however, ultimately most cobalt ends up in soil or sediment, /30/.

The information on the environmental fate and toxicity of cobalt compounds in general is sparse. Data for cobalt suggest a low ability to bioconcentrate in aquatic organisms (BCF below 100). The very few LC₅₀ values found for cobalt indicate that cobalt is toxic or very toxic to aquatic organisms. (LC₅₀ (28 days) for rainbow trout found between 0.2 and 15.6 mg/l), /33/. The Nordic list of suggestions for environmental classification classifies cobalt as "may cause long-term adverse effects in the aquatic environment" (R53). Different cobalt compounds like cobalt chloride, cobalt sulphide, cobalt oxide, and cobalt sulphate are all classified by the Nordic Council of Ministers as "very toxic to aquatic organisms" and "may cause long-term adverse effects in the aquatic environment", /34/.

9.1.2 Manganese driers

Manganese driers used in this project as alternatives to cobalt driers are:

• Manganese 2-ethylhexanoate (CAS-no. 13434-24-7) - Xi R38 ^[2]
• Manganese salt (type and CAS-no. confidential) – classification not known
• Manganese salt of C6-19 branched fatty acid and naphthenic acid (not further specified, CAS-no. confidential) – Xi R38
• Manganese dipropionate (CAS-no. 21129-18-0) – Xi R38
• Manganese (II) isooctanoate (CAS-no. 37449-19-7) – Xi R38
• Manganese isononate (CAS-no. 29826-51-5) – Xi R38
• Manganese compound (confidential) – classification not known

No environmental or health information was found for these specific substances, therefore manganese compounds are described in general.

9.1.2.1 Manganese compounds
Manganese is an essential trace element in humans that plays a role e.g. in bone mineralization, protein and energy metabolism, and cellular protection from damaging free radical species. Manganese deficiency can lead to slowed blood clotting, skin problems, changes in hair colour, lowered cholesterol level, and other alterations in metabolism. However, exposure to high levels of manganese via inhalation or ingestion is toxic, and can cause adverse health effects, /35/36/.

Manganese exists in different oxidation states from –3 to +7, the most common being +4, +3, and +2, both in the environment and in the workplace. In living systems, manganese is found in the +2 valence as an essential element. Most manganese compounds seem to cause the same effects, although it is unknown whether exposure to different manganese compounds results in slight differences in adverse effect. Mn2+ is in general considered to be more toxic than Mn3+, /29/36/37/.

The primary route of absorption of manganese in the human body is via inhalation. The dermal route does not appear to be of significant concern. Given comparable doses, more manganese reaches the brain following inhalation than following ingestion, and most health effects are associated with chronic inhalation exposure, /35/. Once absorbed, manganese is transported to organs like the liver and pancreas where it is rapidly concentrated. Accumulation of manganese in the central nervous system (CNS) occurs more slowly. Manganese does not undergo metabolism in the human body, /37/

For some organic manganese compounds irritation of skin may occur by contact with skin, and some organic manganese compounds have been found to cause allergic contact dermatitis, /36/.

Acute inhalation exposure to high concentration of manganese dust can cause an inflammatory response in the lung, which over time can result in impaired lung function. This lung toxicity results in symptoms like increased incidence of colds, bronchitis and pneumonia, /35/37/.

In chronic inhalation exposure to manganese, the main organ systems affected are the lungs, the CNS, and reproductive system, although effects on other organ systems also have been observed, /35/.

The primary effect of manganese toxicity from inhalation exposure in humans is symptoms of CNS toxicity. Prolonged inhalation of elevated manganese concentrations result in chronic manganese neurotoxicity – a Parkinsonism-like disease called manganism. Initial symptoms of manganism are usually general feelings of weakness, headache, muscle pain, insomnia, nervousness, irritability, speech disturbances and memory loss. Removal of the affected person from the manganese source usually results in reversal of most of the symptoms. However, a continued chronic exposure can result in motor difficulties, clumsiness, muscle cramps, tremors – symptoms similar to Parkinsons disease. The later stages of manganese toxicity are irreversible even though manganese concentrations in the tissues decrease to normal levels upon removal from the manganese source, /36/37/38/.

Manganese can result in reproductive effects, such as decreased libido, impotence, and decreased fertility in men by chronic inhalation exposure. No information is available on the reproductive effects in women, /35/.

In vitro studies show that some chemical forms of manganese (manganese chloride, manganese sulphate) have mutagenic potential. However, in vivo studies are inconsistent, therefore no overall conclusion can be made about the possible genotoxic hazard to humans, /35/. Equally, information about the carcinogenic potential of manganese is limited. U.S. EPA assesses manganese as not classifiable as to human carcinogenicity based on no evidence in humans and inadequate evidence in animals, /36/37/.

In 1995 a Danish occupational medicine clinic investigated the relationship between working with manganese and serious diseases at a steel rolling mill (Stålvalseværket) in Denmark. A clear connection between working with manganese and serious diseases as trembling and lapse of memory was found, and resulted in a strong suspicion that manganese can result in brain damage. The investigation showed that the group of people working with manganese dust was hit the hardest, /38/.

Today, about 50 people in Denmark have received financial compensation for their occupational injury because of working with manganese, and at least the same number of people is waiting for a decision in their occupational injury case. Most of them are not able to work because of their illness, /38/.

Other international investigations have shown that not all people working with manganese are getting sick. Experts agree on the fact that manganese is a hazardous substance, but knowledge of what makes the metal hazardous is lacking. Investigations suggest that inhaled manganese dust will enter the blood stream, enter the brain and cause serious damage. However, it may also be manganese in combination with another metal like lead that is problematic. More research on this field is necessary, /38/. A study that will investigate the mechanism for neurotoxic effect of manganese and the combination effects of manganese has been initiated in Denmark. No results are ready so far as the study is due during 2004.

In the external environment, the oxidation states +2, +3 and +4 are the most stable. Manganese +2 is the most stable oxidation state in water, while manganese +3 and +4 compounds are immobile solids that may be reduced to the soluble manganese +2 by organic matter. Manganese +2 compounds are relatively mobile, as they do not strongly complex to soil and organic matter, and may therefore potentially leach into surface and groundwater. Manganese compounds are not expected to volatilise from water or moist soil surfaces, /29/.

With regard to the aquatic toxicity of manganese, the LC₅₀ (96 h) values for manganese and manganese +2 that are found, leads to a classification of harmful to aquatic organisms or no environmental classification. (Manganese: crayfish 28-51 mg/l; manganese (II) sulphate: fathead minnow 24-37 mg/l, longfin dace 100-169 mg/l), /33/. The Nordic list of suggestions for environmental classification classify manganese (II) sulphate as toxic to aquatic organisms, and may cause long-term adverse effects in the aquatic environment (N, R51, R53), /34/.

Manganese accumulates (up to a factor 40.000) in different kinds of plants, and in some mussels and other marine invertebrates. However, manganese compounds do not bioconcentrate in humans and animals, /29/. A bioconcentration factor (BCF) for different manganese compounds is found between 3 and 61 for different fish (starfish: BCF = 3-61, fathead minnow: BCF = 23, and brown trout: BCF = 18), /33/.

9.1.3 Vanadium driers

Vanadium driers used in this project as alternatives to cobalt driers are:

• Vanadium organophosphate (CAS-no. confidential) - Xn R22 ^[3]
• Vanadium compound (confidential) – classification?
• Vanadium neodecanoate (CAS-no. 60451-07-2) – Xi R38 ^[4]

No environmental or health information was found for these specific substances, therefore vanadium compounds are described in general.

9.1.3.1 Vanadium compounds
In general little information about vanadium compounds exists. The information is primarily on the vanadium metal or inorganic compounds – primarily vanadium pentaoxide.

Vanadium metal has a low toxicity, and does not seem to be dangerous for human health. Pentavalent vanadium and vanadates are the most toxic vanadium substances, /29/39/

Vanadium compounds are in general poorly absorbed when ingested, but are more easily absorbed through the lungs, /40/. The toxic effects are therefore to some extent limited to the respiratory system. Effects like coughing, difficulty in breathing, pneumonia and bronchitis are observed by exposure in industry, /40/41/. Vanadium compounds may cause CNS-toxicity. Effects, like tremors, headaches, tinnitus and changes in the mental status, have been observed, /29/41/.

Vanadium is skin irritant, and vanadium dust (usually vanadium pentaoxide) is severely irritating to eyes, nose, throat and respiratory tract, /29/42/. Still, no clear information is available from animal studies with regard to the potential of vanadium compounds to produce skin or eye irritation or skin sensitisation, /42/.

Some vanadium compounds (primarily inorganic vanadium compounds, e.g. vanadium pentaoxide) have long-term effects and are carcinogenic, mutagenic and have reproductive effects, /39/. Inhalation studies of vanadium pentaoxide in rats and mice show some evidence of carcinogenic activity in rats, and clear evidence of carcinogenic activity in mice, /43/. Furthermore, there is evidence that tetravalent vanadium has the ability to cross the placental barrier to the foetus, /42/, and studies with female rats indicate a possible teratogenic effect. Vanadium pentooxide has to be classified as mutagenic (Mut3) and reprotoxic (Rep3) according to the list of dangerous substances, /24/.

The environmental fate of vanadium is characterised by the fact that a large part is absorbed by organic material, e.g. the sediment. Dissolved in water vanadium will oxidise to the pentavalent state. Vanadium pentaoxide is classified as toxic for aquatic organisms. /39/. Acute LC₅₀ values for aquatic organisms range from 0.2 to about 120 mg/litre, with the majority lying between 1 and 12 mg/litre, /42/. The Nordic list of suggestions for environmental classification classify vanadium pentaoxide as toxic to aquatic organisms, and may cause long-term adverse effects in the aquatic environment (N, R51, R53) as the substance is assessed not to be readily biodegradable, /34/.

A few bioconcentration factors are found: 50 to 600 for fish, and factors 400 and 1900 for phyto- and zooplankton, indicating an ability to accumulate, /29/. However, there is no evidence of accumulation in food chains in marine organisms, /42/.

A recent study by the Danish EPA, /39/, has investigated the present knowledge of a number of "second rank" elements – including vanadium - with regard to use pattern and consumption in Denmark, dispersal into and behaviour in the environment, hazards to human health and potential effects in the environment. The conclusion of the study – with regard to vanadium – is that if the inherent toxicological and ecotoxicological properties of the investigated elements are combined with consumption, use pattern and risk of dispersal into the environment, vanadium is one of the elements that are assessed to be the most critical among the second rank elements at present.

The study concludes that vanadium can be described as a substance that is toxic for aquatic organisms. However, in Denmark, concentrations of vanadium in the environment are primarily found in solid waste, and will therefore not have a significant effect on the aquatic environment. If vanadium driers are to substitute cobalt driers in paints, the vanadium discharged to the aquatic environment will increase, because of discharge of paint residues to the aquatic environment.

9.1.4 Evaluation of the driers

The driers included in the environmental and health assessment are the existing cobalt driers (cobalt naphtenate and cobalt 2-ethylhexanoate) and different manganese and vanadium driers as alternatives. Examples of manganese and vanadium driers are listed above (see the sections "Manganese driers" and "Vanadium driers"). However, some of the alternative driers are confidential, and for all alternatives apply that no specific environmental or health information was found. Therefore, the environmental and health assessment of the driers is carried out on the basis of the group of substances.

Cobalt, manganese and vanadium compounds have in common that the oral and dermal absorption of the substances is low – absorption is more or less limited to absorption by inhalation. Cobalt, manganese and vanadium compounds therefore show some of the same effects, e.g. pneumonia-like symptoms and CNS-damage. Manganese exposure may lead to Parkinsonism-like disease.

Cobalt compounds may lead to allergic contact dermatitis, and the same effect has been seen for some organic manganese compounds. However, for vanadium compounds no clear information is available.

Cobalt compounds are in general found to be possibly carcinogenic to humans (group 2B). For manganese compounds no evidence of carcinogenic effects exists for humans, and the evidence in animals is inadequate. For vanadium carcinogenic effects have been shown, but vanadium compounds are not classified due to its carcinogenicity to humans.

Mutagenic and reprotoxic effects are seen for all three metal compounds. However, mutagenic studies for manganese compounds are inconsistent, and the mutagenic and reprotoxic effects for vanadium are primarily seen for vanadium pentaoxide.

The health profile for air-drying products will be less negative, if cobalt driers are substituted with manganese or vanadium driers, as only cobalt compounds are classified with regard to the carcinogenic effects to humans. The effect is not very obvious because both manganese and vanadium compounds have shown adverse health effects. The adverse effects for vanadium compounds are, though, primarily found for vanadium pentaoxide. Health effects of other vanadium compounds are very sparse. The history of occupational manganese exposure indicates that the adverse health effects primarily are associated with intense exposure over a long period of time.

With regard to ecotoxicity of the driers, the environmental profile will also be less negative, if cobalt driers are substituted with manganese or vanadium driers. Cobalt driers are in general regarded as very toxic or toxic to aquatic organisms, whereas vanadium compounds (vanadium pentaoxide) are toxic and manganese compounds are regarded as harmful to aquatic organisms.

Overall, the environment and health profile of air-drying products will become less negative if cobalt driers are substituted with manganese or vanadium driers, especially as the driers are combined with the same secondary driers as cobalt driers and in approximately the same concentrations. However, this evaluation is based on information about the group of substances alone, as no specific information was found on the alternative manganese or vanadium driers.

9.2 Anti-skinning agents / antioxidants

The anti-skinning agents to be evaluated are the existing anti-skinning agents – methyl ethyl ketoxime and hydroquinone, and the alternatives amino/amido anti-skinning agents and vitamin E.

9.2.1 Methyl ethyl ketoxime

Methyl ethyl ketoxime (CAS-no. 96-29-7) is hazardous by ingestion, and is also harmful by inhalation and in contact with skin, as the substance is readily absorbed through the skin. The substance is a severe eye irritant and is also irritating to the skin, /44/.

Methyl ethyl ketoxime may cause sensitization by skin contact, and is capable of causing allergic skin reactions. The substance has to be labelled with the risk phrases R41 "Risk of serious damage to the eyes" and R43 "May cause sensitisation by skin contact", /24/.

Mutagenic effects have been observed for methyl ethyl ketoxime as well as tumorigenic effects. Methyl ethyl ketoxime is considered to be carcinogenic according to the criteria set by RTECS, /44/. Methyl ethyl ketoxime must be labelled with "Carc Cat. 3" and the risk phrase R40 "Limited evidence of a carcinogenic effect", /24/.

Methyl ethyl ketoxime is not found to be toxic for aquatic organisms. (LC₅₀ 96 h values for fathead minnow are found between 777 and 914 mg/l), /33/. According to the Nordic list of suggestions for environmental classification methyl ethyl ketoxime is not likely to bioconcentrate in aquatic organisms (Log PO_W = 0.65 and BCF = 6), /34/. No data on the biodegradability of methyl ethyl ketoxime was found.

9.2.2 Hydroquinone

Hydroquinone (CAS-no. 123-31-9) is rapidly and extensively absorbed from the gut and trachea of animals. Absorption via skin is slower. Hydroquinone is distributed rapidly and widely among tissues, but hydroquinone and its metabolites are excreted rapid – primarily via the urine. Hydroquinone and its derivatives react with different biological compounds and have effects on cellular metabolism, /45/.

Hydroquinone is hazardous by ingestion, and may actually be fatal if swallowed, /44/. The major signs of hydroquinone poisoning are dark urine, vomiting, abdominal pain, tremors, convulsions and coma, /45/. The substance is harmful if inhaled, and is toxic to lungs, the central nervous system and the mucous membranes. Acute high-level exposure to hydroquinone causes severe effects on the CNS including, tremor, coma, convulsions and death, /45/. Repeated or prolonged exposure to the substance can produce target organ damage.

Hydroquinone is hazardous in case of skin contact, as the substance can be absorbed through the skin. The substance causes severe skin and eye irritation, and may cause allergic skin reactions. The substance is reported to be an active allergen, /29/44/. Hydroquinone must be labelled with the risk phrases R41 "Risk of serious damage to the eyes" and R43 "May cause sensitisation by skin contact", /24/.

Based on animal studies hydroquinone may cause cancer /29/. However, these findings are limited and IARC (International Agency for Research on Cancer) classifies hydroquinone in group 3 i.e. not classifiable as to its carcinogenicity to humans, because of inadequate evidence in humans for the carcinogenicity, /46/. Hydroquinone must be labelled with "Carc Cat. 3" and the risk phrases R40 "Limited evidence of a carcinogenic effect" and R68 "Possible risk of irreversible effects", as well as "Mut Cat. 3" as it is suspected to be a human mutagen, /24/. Gene mutations and DNA damages have been demonstrated in test tube experiments, /45/.

Hydroquinone is highly soluble in water, and will mainly be distributed to the water compartment when released into the environment /45/. Hydroquinone is very toxic to aquatic organisms (LC₅₀ 96 h for fathead minnow 0.05 – 0.4 mg/l) /33/, but may be readily biodegrade and is not likely to bioconcentrate (Log PO_W = 0.59 and BCF = 40), /34/45/. However, the products of degradation are as toxic as the original products. Hydroquinone must be labelled with the risk phrase R50 "Very toxic to aquatic organisms", /24/.

9.2.3 Organic amino compound

Two anti-skinning agents (trial products) with an organic amino and amido compound as the active ingredients have been tested. The test product received contained both an organic amido compound and an organic amino compound. However, the formulation of these anti-skinning agents has been changed since the testing, resulting in the amido compound being excluded from the formulation.

The identity of the compounds is confidential. However, the project group was told the identity of the compounds in return for keeping the identity as a secret. This is the reason why no exact references will be given in this section, as the references may reveal the identity of the substance. Only the amino compound will be described in this section, as the amido compound is no longer relevant after exclusion from the formulation.

The data on the toxicity and ecotoxicity of the amino compound is found in several MSDS's found by use of the Internet, and databases like TOXNET, /47/, and RTECS. However, toxicity and ecotoxicity information about the specific substance is limited.

A couple of MSDS's found by use of the Internet classify the pure organic amino compound in different ways, either as Xn R20/21, Xn R10-20/21-36, Xn R10-20/21-36/37/38-40 or as Xn R10-20/21-36/37/38-40-65 ^[5].

The organic amino compound is not on the list of hazardous substances, /24/. However, the amino compound is adopted on the advisory list for self-classification of dangerous substances, that the Danish EPA has prepared on the basis of predictions by computer models (QSAR models - Quantitative Structure-Activity Relationship). On this list of self-classification the organic amino compound is given the recommended classification Xn R22 (Harmful if swallowed), /27/.

The MSDS's denote an oral LD₅₀ value in rats of about 2200 mg/kg, indicating that the amino compound is slightly toxic to rats. RTECS (The Registry of Toxic Effects of Chemical Substances) lists that the lowest published lethal dose by oral intake for rats is about 1600 mg/kg.

Use of QSAR models indicates that the amino compound have moderate skin penetrability, and that the vapour pressure of the amino compound may cause concern, /26/.

Two of the MSDS's indicate that the amino compound may be a possible sensitiser. An early study has shown an allergic skin reaction in guinea pigs following repeated skin application, but in a more recent study no skin allergy was observed. Use of QSAR models confirms that the amino compound may cause skin allergic reactions, /26/.

One of the MSDS's states that the amino compound may possibly be a mutagen. Information about mutagenicity studies found on TOXNET, /47/, and in RTECS for the substance shows a positive test for gene mutation and DNA effects. However, a number of other mutation tests are negative or show no conclusion.

According to one of the MSDS's there is limited evidence of carcinogenic effects of the amino compound. The National Toxicology Program, /44/, has nominated the substance for toxicological evaluation for carcinogenic effects, because of lack of carcinogenicity data. Use of QSAR models shows a possible indication of carcinogenic effect in female rats, /26/. However, no information about the carcinogenic effect is available at present.

Studies on reproductive effects are negative. No birth defects were observed in rats following oral exposure and in mice after inhalation during pregnancy, even at dosages, which produced adverse effects on the mothers.

Only very sparse information is available on the environmental toxicity of the amino compound and the results regarding biodegradability are inconclusive.

With regard to aquatic toxicity LC₅₀ values of 130 and 150 mg/l (for guppies) are found for the substance, i.e. a fairly low aquatic toxicity, resulting in no environmental classification. Use of QSAR models does not indicate that the amino compound is toxic to aquatic organisms, /26/.

9.2.4 Vitamin E

Vitamin E (CAS-no. 59-02-9) is a yellow viscous fat-soluble oil that exists in eight different forms. Alpha-tocopherol, which is the form used in this project as alternative anti-skinning agent, is the most active form of vitamin E in humans, and is a PO_Werful biological antioxidant.

Vitamin E is an essential vitamin, which we daily get via food (e.g. nuts and green leafy vegetables). Vitamin E is vital for protecting the nerve and muscle cell function. Vitamin E deficiency is rare in humans, but can cause symptoms like dry skin, eczema, decreased clotting time and easy bruising, /48/.

Vitamin E is usually non-toxic. Daily intake of vitamin E supplements (e.g. 200 to 600 mg vitamin E) is considered to be safe and unlikely to cause adverse side effects. However, intakes of large doses have been known to cause effects like nausea, diarrhea, fatigue, headache, rash and abdominal pain, but is rare, /29/48/.

A Canadian experiment with mice showed that vitamin E might reduce the average mutation frequency in tumour cells by up to 84%. The experiment suggests that vitamin E acts to protect cells against the effects of free radicals (potentially damaging by-product of metabolism). Free radicals can cause cell damage that may lead to the development of cancer. In summary the results suggest that vitamin E may exert antimutagenic/anticancer properties, /49/.

Other studies show that vitamin E protects against prostate, stomach and colon cancer, /50/51/, reduce skin tumour incidence, /52/, and that Vitamin E may protect the liver and the rest of the body against environmental pollutants such as ozone and other constituents of smog, /48/.

A few animal experiments on reproduction and teratogenicity have been carried out, and vitamin E shows no effect, /29/52/.

An experiment with mice indicates that the skin sensitivity commonly associated with UVB induced sunburn ise significantly reduced by topical application of tocopherol acetate, even after the exposure has occurred. Vitamin E has therefore been prescribed for therapeutic use on inflammatory skin disorders. In contrast, topical application of vitamin E on human skin has caused inflammation of the surface of the skin (contact dermatitis), and allergic reactions to creams containing vitamin E have been seen in patch tests, /29/. Furthermore, adults have developed skin rashes when given a high dose of Vitamin E (2 to 3 g/day) over a period. However, the reported effects of vitamin E on human skin are very rare, /29/.

No information on environmental fate and toxicity was found for vitamin E.

9.2.5 Evaluation of the anti-skinning agents/antioxidants

The anti-skinning agents included in the environmental and health assessment are the existing substances methyl ethyl ketoxime and hydroquinone and the alternatives vitamin E and a confidential organic amino compound. The evaluation has been carried out for the specific substances as the confidential identity of the organic amino compound was revealed to the project group. However, specific information was sparse.

The existing anti-skinning agents (methyl ethyl ketoxime and hydroquinone) are both hazardous substances by ingestion and harmful by inhalation. Both substances are severe eye and skin irritants and may produce allergic effects. They should both be labelled carcinogenic cat.3, i.e. limited evidence of carcinogenic effects. Hydroquinone is furthermore a suspected mutagen, whereas mutagenic effects have been observed for methyl ethyl ketoxime.

The health profile of air-drying products will not necessarily be improved if the existing agents are substituted with the organic amino compound. The organic amino compound is less toxic (harmful by ingestion and inhalation) and less irritating than the existing anti-skinning agents, and studies on skin allergy are mixed (positive and negative results). However, some of the MSDS's found for the amino compound, classify the amino compound as "limited evidence for carcinogenic effect", and information available from RTECS suggests that the organic amino compound may be genotoxic.

The health profile will be improved if the existing anti-skinning agents are substituted with vitamin E. Vitamin E is basically non-toxic, has shown both anti-mutagenic and anti-carcinogenic effects, and has been used for therapeutic use on inflammatory skin disorders – even though allergic reactions have been seen.

With regard to ecotoxicity hydroquinone is a problem. Hydroquinone is very toxic to aquatic organisms, whereas methyl ethyl ketoxime is not. Of the alternatives, the organic amino compound has a better environmental profile than hydroquinone. The amino compound has a low aquatic toxicity. No information about the ecotoxicity of vitamin E was found.

9.3 Petroleum distillates

The petroleum distillates are present in most of the drier products and the anti-skinning agents in considerable amounts. The petroleum distillates used are different types of white spirit, se Table 9.1.

According to the "European list of dangerous substances", /24/, most of the petroleum distillates are classified as carc2; R45 Xn (Harmful: may cause cancer); R65 (Harmful: may cause lung damage if swallowed).

Table 9.1
The petroleum distillates used in the drying and anti-skin alternatives

1 Classification according to the list of dangerous substances, /24/.

Xn Harmful.

R45 May cause cancer.

R48/20 Harmful: danger of serious damage to health by prolonged exposure through inhalation.

R65 Harmful: may cause lung damage if swallowed.

The primary route of exposure to white spirit is by inhalation of vapours. White spirit vapour is readily absorbed by inhalation and distributed from the blood to other tissues and fat in the human body. Sparse information on the elimination of white spirit exists, but the elimination rate seems to be slow.

In general, white spirit has a low acute toxicity by inhalation, ingestion and by absorption through skin. Studies show that the central nervous system (CNS), respiratory system, liver and kidney generally are the targets for white spirit toxicity.

Acute CNS symptoms such as headache, "drunkenness", dizziness and fatigue have been reported in several cases of occupational exposure. The effects of long-term exposure to white spirit are shown by painter's syndrome. Memory impairment, fatigue, irritability, dizziness, impaired concentration, headache, anxiety and apathy have been the long-term effect of white spirit.

White spirit is a slight to moderate skin irritant, and eye irritation has been reported in connection with acute exposure to white spirit, /53/.

IARC (International Agency for Research on Cancer) evaluates residual (heavy) fuel oil as "possibly carcinogenic to humans (group 2B)" because there is found sufficient evidence for the carcinogenicity in experimental animals of residual (heavy) fuel oils, /54/. For painters, evidence has been found of increased cancer risks, particular in the lung and bladder, /53/.

No conclusive findings exist on the reproductive effects in humans for white spirit. Still, studies suggest that parental exposure to solvents may have an unwanted effect on the offspring. However, there is no adequately reported information directly related to white spirit, /53/.

When released in the environment, the lower molecule weight alkanes and aromatics of the white spirit will evaporate and undergo photodegradation in the atmosphere. The higher molecule weight alkanes tends to be sorbed to organic matter in soil and water, /53/.

Biodegradation of white spirit is expected to be fairly quick (90% reduction in soil concentration over a four month period), /53/.

Only few studies on aquatic toxicity of white spirit are available. These findings indicate that white spirit is moderately toxic to aquatic organisms (LC₅₀ (96-h) values range from 0.5 to 5 mg/litre), /53/. However, because of the volatility and the low bioavailability of its constituents following sorption to soil/sediment, white spirit, although it is moderately toxic to aquatic organisms, is unlikely to present significant hazards to the environment.

9.3.1 Evaluation of petroleum distillates

The petroleum distillates are used in both driers and anti-skinning agents in considerable amounts. The petroleum distillates have, as described above, several adverse effects on human health – the worst being possibly carcinogenic, and are moderately toxic to aquatic organisms.

To improve the overall profile of the driers and anti-skinning agents, it is therefore necessary to use other organic solvents, with a better health profile, for dissolving the driers and the anti-skinning agents, or at least to use as low a content of the petroleum distillates as possible.

Footnotes

[2] Xi – Irritating substances, R38 – Irritating to skin.

[3] Xn – Harmful substances, R22 – Harmful if swallowed.

[4] Xi – Irritating substances, R38 – Irritating to skin.

[5] R10 – Flammable. R20/21 – Harmful by inhalation and in contact with skin. R36 – Irritating to eyes. R36/37/38 – Irritating to eyes, respiratory system and skin. R40 - Limited evidence of carcinogenic effect. R65 – Harmful: may cause lung damage if swallowed.

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Version 1.0 December 2003, © Danish Environmental Protection Agency