EXECUTIVE SUMMARY
Hydroxycitronellal, a fragrance ingredient used to impart a pleasant floral odour to numerous consumer products, has been chosen for a full risk assessment principally because of its known skin sensitising properties. While this risk assessment attempts to address all possible endpoints, the low volumes of use of hydroxycitronellal and low levels of inclusion in these consumer products have led to this risk assessment giving a preponderant emphasis to dermal sensitisation.
Hydroxycitronellal (3,7-dimethyl -7 hydroxyoctanal) CAS 107-75-5, EINECS 203-518-7 is low molecular weight (172) substance that is generally a viscous liquid although it congeals at temperatures below 23°C. It has considerable water solubility (23.8 g/l) and low lipophilicity (log Pow: 1.5-2.2). It has a low estimated vapour pressure of 0.76 Pa at 25°C and a low calculated Henry's constant (log H: -2.26).
Hydroxycitronellal is used as an ingredient in fragrances and is found in a wide variety of consumer products. These include cosmetics like soaps, shampoos, detergents, cosmetics and perfumes and household cleaning and maintenance products. Maximum levels of use in these latter products are 70 ppm in laundry detergents, 70 ppm in fabric conditioners, 90 ppm in dish-washing products and less than 10 ppm in toilet cleaners and hard surface cleaners.
Hydroxycitronellal used in Europe is produced primarily inside the European Union in quantities estimated to be 88,000 kg/year. It is estimated that 35% of this (35,000 kg/year) is used in household cleaning and maintenance products.
Environmental Assessment
Exposure: The current risk assessment is made according to the "HERA detergent scenario" and the EUSES regional methodology. Highest regional levels were calculated to be c. 1.6 x 10-5 mg /kg in sediments, 8 x 10-6 mg/l in surface water and 1.4 x 10-10 mg/m3 in air.
Hazards: Hydroxycitronellal is readily biodegradable. Acute toxicity studies showed that it was harmful to algae (96h- EC50: 68 mg/l) but not to daphnids (48h-EC50: 410 mg/l).
Possible no effect levels: In the absence of test data, assessment factors and QSARs have been used to give PNECS of 7.8 µg/l for aquatic organisms, 9.6 µg/kg bw for terrestrial organisms and 17 µg/kg bw for sediment-dwelling organisms.
Risk characterisation: Margins of exposure are well below 1 for all environmental compartments (1 x 10-3 for aquatic organisms in regional water, 1.2 x 10-6 for terrestrial organisms and 9 x 10-4 for organisms in sediments. Even if the total usage volume of 88 tonnes/year (i.e. including use in cosmetics), these regional risk characterisation ratios are all less than 1 x 10-3.
Conclusion: Current use levels and volumes of hydroxycitronellall in household cleaning products does not concern with regard to possible effects on the environment.
Human Health Assessment
Consumer exposure: This risk assessment has been restricted to direct or indirect exposure to consumers arising from the use of laundry detergents, fabric conditioners, hard surface cleaners, toilet cleaners, cleaning sprays and dish-washing products. In addition to considering exposure in terms of the quantities potentially entering the body, this assessment has focused on exposure in terms of the quantity likely to be deposited on the skin surface as this is the exposure factor that is critical to the induction of allergic contact dermatitis.
Highest exposures: Accidental exposure from splashes of spills (0.9 µg/cm2), represent the highest potential skin exposure doses likely to induce or elicit allergic contact sensitization. Hand washing using laundry pre-treatment liquids is estimated to give the highest levels of direct or indirect exposure in terms of quantities penetrating the skin (0.14 µg/kg bw/day). Total aggregate systemic exposure from all routes and all exposure scenarios is estimated to not exceed 0.17 µg/kg bw/day.
Hazards: Studies on animals and humans demonstrate that hydroxycitronellal is a skin sensitiser. This is substantiated by clinical data that show widespread under-lying allergy to hydroxycitronellal although very few cases of allergy are clearly attributable to the presence of hydroxycitronelal in any specific consumer products.
Hydroxycitronellal has a low order of acute toxicity by the oral and dermal routes. Inhalation is not considered a significant route of exposure. Systemic toxicity studies have shown that levels of 400 mg/kg/day are well tolerated by rats over two years although these studies do not meet modern testing requirements. Hydroxycitronellal is negative in bacterial and mammalian genotoxicity screens and was not tumorigenic in the above-mentioned 24-month feeding study.
Hydroxycitronellal shows low to moderate skin and eye irritancy while a limited inhalation study has shown some irritancy by this route too.
Critical end-points and threshold levels: Skin sensitisation and systemic toxicity were considered to be the critical end-points. A No Expected Sensitization Level (NESL) of 2.95 mg/cm2 has been determined using a weight of evidence approach from a large number of predictive tests carried out on human and animal subjects. There is evidence to show that although the threshold for elicitation of allergic responses in prior-sensitised individuals may be as low as 1 µg/cm2, these endpoints cannot be used in risk assessment as they are neither reliable nor unique determinants of elicitation.
In the absence of a reliable NOAEL for systemic toxicity, two measures were taken as a basis for risk assessment. One was a NOEL estimated by JECFA to be 250 mg/kg bw/day. The other was the Threshold of Toxicological Concern (TTC) of 30 µg/kg bw/day based on a large data set NOAELs of substances that have been similarly classified chemical structures.
Risk characterisation: Margins of exposure for skin sensitization induction from different exposure scenarios were found to vary between over a million and 3,000. Aggregate margins of exposure for systemic effects from all products combined were over one million based on the NOEL and above 170 based on the TTC (which already incorporates other safety factors).
Conclusion: The use of hydroxycitronellal at current levels in household cleaning products does not raise any safety concerns with regard to its potential to cause allergic contact dermatitis and adverse systemic effects. |
