A Effect concentration based on measured concentrations.
^B 95% confidence limits.
^C The ranges include tests with C₁₂, C₁₄, C₁₆, C₁₈, and C_20-22.

5.1.3 Effects on human health

Toxicokinetics and acute toxicity

The few available absorption studies conducted with cationic surfactants indicate that absorption occurs in small amounts through the skin (Bartnik and Wingen 1979; SFT 1991). Percutaneous absorption of radiolabelled C₁₂ ATMAB in 3% aqueous solution (applied to an 8 cm² area with occlusion) in the rat was low and corresponded to 0.6% of the applied ¹⁴C activity in 72 hours. Most of the absorbed surfactant was excreted in the urine, i.e. 0.35% of the applied ¹⁴C activity within the first 24 hours, whereas 13.2% remained on the skin after rinsing. Cutaneous application of the surfactant without rinsing resulted in a greater degree of percutaneous absorption (3.15%) in 48 hours. In the rat elimination after parenteral administration was rapid and was effected primarily via the urine, - more than 80% of the radioactivity was eliminated within 24 hours of application (Bartnik and Wingen 1979).

About 80% of the ¹⁴C activity was found in the gastrointestinal tract 8 hours after oral administration of ¹⁴C-labelled C₁₆ ATMAB . Only small amounts of the applied radioactivity were found in the urine and in the blood plasma. This indicates poor intestinal absorption. Similar small amounts of ¹⁴C were found in the liver, kidneys, spleen, heart, lungs and skeletal muscles. Within 3 days of ingestion, 92% of the administrated radioactivity had been excreted in the faeces and 1% in the urine. No appreciable enterohepatic circulation of the radioactivity was found (Isomaa 1975).

The acute oral toxicity of alkyltrimethylammonium salts (Table 5.4) is somewhat higher than the toxicity of anionic and nonionic surfactants. This may be due to the strongly irritating effect which cationic surfactants exhibit on the mucous membrane of the gastrointestinal tract (SFT 1991). Cationic surfactants are generally about 10 times more toxic when administrated by the intravenous route compared to oral administration (Falbe 1986; SFT 1991).

Table 5.4
Acute toxicity (LD50) after oral administration of alkyl trimethylammonium salts.

Skin and eye irritation

Skin irritation depends on surfactant concentration. Regardless of the structure, cationic surfactants lead to serious destruction of the skin at high concentrations. Solutions of approximately 0.1% are rarely irritating, whereas irritation is usually pronounced at concentrations between 1.0 and 10.0% surfactant (CIRP 1997). C₁₆ ATMAC was severely irritating to rabbit skin in a concentration of 2.5%. The surfactant was applied to intact and abraded sites and scored after 34 hours. Then the skin was rinsed and then scored again after 48 hours. The erythema and Eschar Index was 3.75 (maximum 4) and the edema Index was 2.0 (maximum 4) (CIRP 1997).

With regard to eye irritation, cationic surfactants are the most irritating of the surfactants (Bartnik and Wingen 1979; SFT 1991). The longer chained alkyltrimethylammonium salts are less irritating to the rabbit eye than the shorter alkyl chain homologues (CIRP 1997). C₁₀ ATMAB, C₁₂ ATMAB, and C₁₆ ATMAC were tested in concentrations between 0.1 and 1.0% in water and were found to be significantly irritating or injurious to the rabbit eye. A 5% solution of C₁₈ ATMAC was instilled into the eyes of guinea pigs, and this concentration was very irritating with a total PII (The Primary Irritation Index) score of 96 (maximum 110) (Bracher et al. 1987).

A homologous series of ATMAB produced very little swelling of the stratum corneum and some homologues produced a shrinkage of the stratum corneum after prolonged exposure (Jungerman 1970; Putterman 1977; Tupker 1990).

Many proteins in the skin are considerably more resistant to the denaturating effects of cationic surfactants compared to those of anionic surfactants. As cationic surfactants frequently have a lower critical micelle concentration than the anionic surfactants, a saturation of the surfactant/protein complex is prevented by the formation of micelles (SFT 1991). Compared to a representative anionic surfactant, the cooperative binding with subsequent protein denaturation requires about a tenfold higher concentration of a cationic surfactant. Contrary to the irreversible denaturating effect of sodium dodecyl sulfate (C₁₂ AS), the adverse effects of some cationic surfactants on proteins may be reversible (Falbe 1986). Cationic surfactants can interact with proteins or peptides by polar and hydrophobic binding. Polar interactions result in electrostatic bonds between the negatively charged groups of the protein molecule and the positively charged surfactant molecule. For example, the enzyme, glucose oxidase, is deactivated by C₁₆ ATMAB through the formation of an ion pair between the cationic surfactant and the anionic amino acid side-chain of the enzyme molecule (Falbe 1986).

Sensitization

A repeated insult patch test of C₁₆ ATMAC was conducted with 114 volunteers. Seventeen days after the last induction of 0.25% surfactant, a challenge patch of 0.25% was applied. No sensitization was observed (CIRP 1997).

Subchronic/Chronic toxicity

C₁₆ ATMAB was administered at concentrations of 10, 20, and 45 mg/kg/day via the drinking water to rats for one year. The only effect observed was a decrease in body weight gain in the 45 mg/day dose group (Isomaa et al. 1976).

Reproductuive toxicology

No embryo toxic effects were seen, when C₁₈ ATMAC was applied dermally to pregnant rats during the period of major organogenesis (day 6-15 of gestation). The concentrations of C₁₈ ATMAC were 0.9, 1.5 and 2.5%. There was no increase in the incidence of fetal malformations (Palmer et al. 1983). C₁₆ ATMAB was not teratogenic in rats after oral doses. Mild embryonic effects were observed with 50 mg/kg/day, but these effects were attributed to maternal toxicity rather than to a primary embryonic effect. Lower doses of C₁₆ ATMAB showed no embryo toxic or teratogenic effects (CIRP 1997).

Mutagenicity

C₁₆ ATMAC was studied in in vitro short-term tests to detect potential mutagenic effects. Cultures of Syrian golden hamster embryo cells were used for an in vitro bioassay. No in vitro transformation of hamster embryo cells was induced, and C₁₆ ATMAC was not mutagenic in Salmonella typhimurium (Inoue and Sunakawa 1980). No mutagenic effects or genetic damages were indicated in a survey of nine short-term genotoxicity tests with C₁₆ and C₁₈ ATMAC (Yam et al. 1984).

Classification

Most undiluted cationic surfactants satisfy the criteria for classification as Harmful (Xn) with R22 and as Irritant (Xi) for skin and eyes with R38 and R41. In addition, certain surfactants will satisfy the criteria for classification as Corrosive with R34 in addition to the acute toxicity (SFT 1991).

According to CESIO, C_8-18 ATMAC (i.e., lauryl, coco, soya, and tallow) are classified as Corrosive (C ) with the risk phrases R22 (Harmful if swallowed) and R34 (Causes burns). C₁₆ ATMAC is classified as Harmful (Xn) with the risk phrases R22 (Harmful if swallowed), R38 (Irritating to skin), and R41 (Risk of serious damage to eyes). C_20-22 ATMAC are classified as Irritant (Xi) with R36/38 (Irritating to eyes and skin) (CESIO 2000).

The maximum allowed concentration of C_12-22 alkyltrimethylammonium salts (bromide or chloride) in cosmetics is 0.1% (Cosmetic Directive 2000).

5.2 Dialkyldimethylammonium salts

Dialkyldimethylammonium chlorides (DADMAC) are used as antistatic agents in cosmetic products including hair conditioners and hair coloring preparations. Furthermore, DADMAC are used as biocides in industrial cleaning agents and, to a minor extent, all purpose household cleaning agents. The alkyl chains of DADMAC are normally linear, although DADMAC containing at least one branched alkyl chain are also used. The general structure of DADMAC is indicated below.

The alkyl chain, R, usually contains 10-16 carbon atoms. The length of the alkyl chains of specific structures is indicated by, e.g., C₍₁₂₎₂ for a DADMAC with two C₁₂ alkyl chains.

5.2.1 Environmental fate

Aerobic biodegradability

The ultimate biodegradability of DADMAC has been examined in several standard biodegradation tests. As for ATMAC, the recalcitrance of DADMAC in screening tests increases with increasing alkyl chain length. This is particularly evident from the studies of Masuda et al. (1976; cited in Ginkel 1995) which indicated that the biodegradability in the MITI test of various DADMAC was 50% of ThOD for C₍₁₀₎₂ and 0% for alkyl chain lengths in the range of C₍₁₂₎₂ to C₍₁₈₎₂. The duration of these tests was 10 days. As also noted for ATMAC, the description of the studies of Masuda et al. does not include information on the inoculum used in the tests. DADMAC with branched alkyl chain(s) like, e.g., decylisononyldimethylammonium chloride are expected to degrade more slowly than similar homologous with linear alkyl chains. Studies by Ginkel et al. (2000) show that DADMAC were transformed in laboratory column experiments in which a slow release of the test compounds were ensured by pre-sorption of the quaternary ammonium salts onto a silica gel. Complete removal of C₍₁₀₎₂ DADMAC, as indicated by HPLC analyses of column effluents, were obtained within 4 days after inoculation of the columns with a pure culture of a bacterium which was able to utilize C₍₁₀₎₂ DADMAC for growth (Table 5.5). In a similar experiment, the same pure culture transformed C₍₁₈₎₂ DADMAC completely after approximately 8 days. A C_(16-18)2 DADMAC (ditallow hydrogenated) was transformed in columns inoculated with river water which indicates that microorganisms capable of a primary degradation of DADMAC are common (Ginkel et al. 2000). These results indicate that the poor biodegradability in standard screening tests is not necessarily due to an inherent recalcitrance of DADMAC as other factors like, e.g., toxicity and a slow desorption of the cationic surfactant from surfaces may limit biodegradation. Studies in which ¹⁴C-labelled C_(16-18)2 DADMAC (ditallow) was added to semi-batch reactors at 2.1 mg/l as a complex with LAS confirm that the entire DADMAC molecule can be ultimately biodegraded. In the reactors, the ¹⁴CO₂ recovered from mineralization of three radiolabelled forms of C_(16-18)2 DADMAC, i.e. [¹⁴C]methyl-, [¹⁴C]C₁-alkyl-, and [¹⁴C]uniform-C-labelled, corresponded to between 22 and 53% of the added ¹⁴C after 39 days, whereas the primary biodegradation in the same period was somewhat higher, i.e. 59-81% of the initial level (Sullivan 1983). The data in Table 5.5 show that the methyl groups bound to the quaternary nitrogen were more susceptible to biodegradation than the carbons in the alkyl chains. A comparison between the biodegradation of DADMAC (Sullivan 1983) with the C₁₈ ATMAC degradation in the studies of Games et al. (1982) indicates that DADMAC are degraded at a considerably slower rate than ATMAC.

Table 5.5
Ultimate and primary biodegradability of dialkyldimethylammonium chlorides under aerobic conditions.

A short-chained C₍₈₎₂ DADMAC was ultimately biodegraded at a concentration of 0.5 mg/l in acclimated river water. The half-lives calculated from the carbon dioxide produced were 4.9 days in the presence of sediment and 13.8 days without sediment (Larson 1983; Larson and Vashon 1983; both cited in Ginkel 1995).

Anaerobic biodegradability

The information on the biodegradability of cationic surfactants under anoxic conditions is scarce. One study has demonstrated that the concentration of quaternary ammonium salts did not decrease, or only slightly decreased, in an anaerobic digester (Janicke and Hilge 1979, cited in Ginkel 1995).

Bioaccumulation

The bioconcentration of DADMAC has been investigated in studies with bluegill sunfish (Lepomis macrochirus) and fathead minnow (Pimephales promelas). As described for ATMAC in Section 5.1.1 the term CR was used to indicate the bioconcentration which was determined by use of ¹⁴C-labelled model compounds. The CR was determined to 32 for C_(16-18)2 DADMAC (Lepomis macrochirus) and 104 for C₍₁₈₎₂ DADMAC (Pimephales promelas) (Tolls et al. 1994).

5.2.2 Effects on the aquatic environment

Algae

Algae are very sensitive to dialkyldimethylammonium salts as also noted for the alkyltrimethylammonium salts. The toxicity of DADMAC and DADMAMS to algae is characterized by EC50 values below 1 mg/l (Table 5.6).

Table 5.6
Effects of dialkyldimethylammonium salts to algae.