| Front page | | Contents | | Back | | Printing instructions |

Identification and assessment of alternatives to selected phthalates

Annex 4 Background data for the environmental and health assessment

Diethylene glycol dibenzoate, DEGD

Identification of the substance
CAS No.	120-55-8
EINECS No.	204-407-6	[1]
EINECS Name	Oxydiethylene dibenzoate	[1]
Synonyms	Diethylene glycol dibenzoate DEGD
Molecular Formula	C18H18O5	[1]
Structural Formula
Major Uses	Plasticizer	[3]
IUCLID	Is listed as a LPV chemical	[1]
EU classification	This substance is not classified in the Annex I of Directive 67/548/EEC as such, but it may be included in one of the group entries.	[1]
Physico-chemical Characteristics
Physical Form	Colourless liquid with mild ester odour	[3], [4]
Molecular Weight (g/mole)	314.4	[2]
Melting Point/range (°C)	28 ºC	[2]
	24 ºC	[4]
	33.5ºC	[6]
Boiling Point/range (°C)	236 ºC (at 0.7 kPa)	[2]
	225-227 ºC (at 3 mm Hg)	[3]
Decomposition Temperature (°C)	> 230 ºC	[4]
Vapour Pressure (mm Hg at °C)	1.3 x 10-7 mm Hg (at 25 ºC) [1.73 x 10-5Pa] 3.2 x 10-6 mm Hg (at 50 ºC) [4.26 x 10-4Pa] 5.1 x 10-4 mm Hg (at 100 ºC) [6.79 x 10-2Pa]	[4]
Density (g/cm3 at °C)	1.2 (at 20 ºC)	[2], [3]
Vapour Density (air=1)	9.4	[2]
Henry’s Law constant (atm/m³/mol at °C)	7.0 x 10-10	[4]
	3.0 x 10-12 at 25ºC	[3], [6]
Solubility (mg/l water at °C)	Soluble in water	[3]
	38.3 mg/l (at 30 ºC and pH 7)	[4]
Partition Coefficient (log Pow)	3.2	[4]
	3.04	[7]
pKa	-
Flammability	-
Explosivity	-
Oxidising Properties	-
Migration potential in polymer	-
Flash point (ºC)	232 ºC	[2]
Viscosity (mPas)	110 (at 20 ºC)	[3]
Atmospheric OH rate constant cm³/(molecule sec)	1.9 x 10-11 at 25ºC	[6]
Emission Data
During production
Exposure Data
Aquatic environment, incl. sediment	Diethylene glycol dibenzoate's production and use as a plasticizer may result in its release to the environment through various waste streams.	[3]
Terrestrial environment	Diethylene glycol dibenzoate's production and use as a plasticizer may result in its release to the environment through various waste streams.	[3]
Sewage treatment plant	-
Working environment	NIOSH (NOES Survey 1981-1983) has statistically estimated that 25,414 workers (10,937 of these are female) are potentially exposed to diethylene glycol dibenzoate in the USA. Occupational exposure may be through inhalation and dermal contact with this compound.	[3]
Consumer goods	-
Man exposed from environment	-
”Secondary poisoning”	-
Atmosphere	-
Dermal	-
Toxicological data
Observations in humans	Observed symptoms: Nausea, vomiting and headaches; with continued use obdominal pain, polyuria followed by oliguria, anuria and renal failure. Also drowsiness, coma, respiratory arrest and pulmonary edema. Range of toxicity: A) The average fatal dose is difficult to estimate. Much of the data is from historical sources or from epidemics that have occurred in patients in third world countries with limited access to medical care. Extrapolation from these sources must therefore be interpreted with caution. B) The average fatal dose in people who drank a sulfanilamide elixir with diethylene glycol as the vehicle was approximately 1 ml (72% concentration of DEG) per kilogram body weight. However, the actual reported fatal doses were highly variable. C) Adult 1) Three men died after consuming approximately 2 to 3 cups (473 – 709 ml) each of 100% diethylene glycol, as an ethanol substitute. 2) A 56-year-old man died after ingesting 8 ounces (236 ml) of 100% diethylene glycol in a suicide attempt. 3) Adults who ingested sulfanilamide contaminated with diethylene glycol survived doses of 1 to 240 milliliters (of a 72% solution). D) Pediatric 1) Median diethylene glycol dose that was fatal in 85 (98%) of 87 children was estimated to be 1.34 ml/kg (range 0.22 to 4.42 ml/kg). Twelve children ingested less than 1.0 ml/kg. 2) Forty-nine children survived ingestion of a median dose of 0.67 ml/kg (range of 0.05 - 2.48 ml/kg) diethylene glycol present in contaminated acetaminophen syrup.	[3]
Acute toxicity
Oral	LD50 = 4190 mg/kg body weight (rat, combined)	[4], [5]
	LD50 = 2830 mg/kg body weight (rat)	[6]
Dermal	LD50 > 2000 mg/kg body weight (rat, combined)	[4], [5]
	LD50 = 20 ml/kg body weight (rabbit)	[6]
Inhalation	LC50 (4 h, mist) > 200 mg/l (rat)	[5]
Other routes	-
Skin irritation	No dermal reaction was reported following a single semi-occlusive application of diethylene glycol dibenzoate to intact rabbit skin for 4 hours.	[5]
Eye irritation	A single instillation of diethylene glycol dibenzoate into the eye of the rabbit elicited transient very slight conjunctival irritation only. No allergic skin reaction was reported in guinea pigs after repeated skin contact (intradermal and topical) using the Magnusson and Kligman method.	[5]
Irritation of respiratory tract	-
Skin sensitisation	Not sensitising to Guinea pig	[4]
Subchronic and Chronic Toxicity
Oral	NOAEL = 1000 mg/kg/day (rat, 13 weeks) Diethylene glycol dibenzoate was administered to rats by dietary admixture to achieve dosages of 0, 250, 1000, 1750 or 2500 mg/kg/day over 13 weeks. Selected Control and Group 5 animals were subsequently maintained off dose for 4 weeks to assess reversibility of any treatment related changes. There were no findings of toxicological importance at a dosage of 1000 mg/kg/day or below. In animals receiving 1750 or 2500 mg/kg/day, there was an adverse effect on bodyweight gain, changes in clinical pathology parameters and an increased incidence/degree of haemosiderosis in the spleen. In addition, at 2500 mg/kg/day, a few treatment-related clinical signs were evident, minimal periportal hepatocyte hypertrophy was noted in both sexes. Plasma enzyme activities (transaminases and/or AP or OCT) were elevated at Week 13 in rats receiving 1750 or 2500 mg/kg/day with an associated minimal increase in liver weight, At necropsy, minimal periportal hepatocyte hypertrophy was detected only at 2500 mg/kg/day. The slight effects in the liver may be a physiological adaptation to treatment at the highest doses. Following 4-weeks recovery, most enzyme activities were normal, liver weights were unremarkable and there was no residual hepatic pathology. Epithelial hyperplasia was detected in the colon of males and the caecum of both sexes. In general, however, dosages of up to 2500 mg/kg/day of diethylene glycol dibenzoate were tolerated. When selected animals previously receiving 2500 mg/kg/day were maintained off-dose for 4-weeks, all treatment related changes showed evidence of, or complete, recovery.	[4], [5]
	No effects were reported in dogs administered up to 300 mg/kg/day of diethylene glycol dibenzoate in their diet for 90 days.	[5]
Inhalation	-
Dermal	-
Metabolism	Metabolism in the Rat. The metabolism of diethylene glycol dibenzoate was studied after both single oral low level (50 mg/kg) and high level (750 mg/kg) doses to groups of 4 male and 4 female rats. The tissue distribution of radioactivity was studied after low-level doses. The proportions and nature of metabolites were also investigated. Virtually all of single oral doses of 50 and 750 mg/kg of diethylene glycol dibenzoate administered to Sprague-Dawley CD rats were adsorbed, metabolized and excreted in the urine within 24 hours of administration. Diethylene glycol dibenzoate was metabolized via hydrolysis of the ester bonds to benzoic acid; this free acid was then conjugated with either glycine (major pathway) or glucuronic acid (minor pathway) prior to excretion.	[4]
Mutagenicity, Genotoxicity and Carcinogenicity
Mutagenicity	S.typhimurium and E.coli (metabolic activator Sprague-Dawley rat liver (S9)) Cytotoxic conc: No toxicity with or without metabolic activation Genotoxic conc: No genotoxic effects observed with or without metabolic activation No evidence of mutagenic activity in this bacterial system.	[4]
	Mouse lymphoma (metabolic activator Sprague-Dawley rat liver (S9)) Genotoxic Effects: In the absence of S9-increases in mutant frequency were observed 350 µg/ml on Test 1 and 200 and 325 µg/ml in Test 2. The increases were not 100 above the control level and were within the historical control range. It was concluded that diethylene glycol dibenzoate did not demonstrate mutagenic potential in the absence of S9 mix. There was no substantive increases in mutant frequency observed in the presence of S9 mix. It is concluded that diethylene glycol dibenzoate did not demonstrate mutagenic potential in this in vitro gene mutation assay	[4]
Chromosome Abnormalities	Chinese Hamster Lung (metabolic activator Sprague-Dawley rat liver (S9)) Genotoxic Effects: No statistically significant increases in the proportion of aberrant cells, when compared to the solvent control, were seen in either the presence or the absence of S9 mix. A small response seen in the first test, with S9 mix, was not reproduced in the repeat test or at the later harvest. This response was not considered to be indicative of clastogenic activity.	[4]
Other Genotoxic Effects	-
Estrogenic activity	Rat Diethylene glycol dibenzoate for Estrogenic Activity Using Vaginal Cornification and the Uterotrophic Response in the Ovariectomized Adult Rat as the Endpoints. Diethylene glycol dibenzoate did not induce vaginal cornification at doses of 500, 1000, 1500 or 2000 mg/kg/day for 7 days by oral gavage in ovariectomized adult Spraque-Dawley (CD) rats. Diethylene glycol dibenzoate did not stimulate a uterine weight increase or an increase in the uterine weight to final body weight ratio at doses of 500, 1000, 1500 or 2000 mg/kg/day for 7 days. When compared with the vehicle control (corn oil) and positive control (diethylstilbestrol), these data demonstrate that Diethylene glycol dibenzoate did not exhibit estrogenic activity up to and including the maximally tolerated dose.	[4]
Carcinogenicity	-
Reproductive Toxicity, Embryotoxicity and Teratogenicity
Reproductive Toxicity	Rat (38 weeks duration) The evidence from this study suggested that a dietary concentration of 10,000 ppm should be considered as the No-Observed-Adverse-Effect-Level (NOAEL) for the FO and Fl parent animals. The No-observed-Adverse-Effect-Level (NOAEL) for the developing offspring is considered to be 3300 ppm. The No-Observed-Effect-Level (NOEL) for reproductive parameters is considered to be 10000 ppm.	[4]
Teratogenicity	-
Developmental toxicity	Rat (20 days duration from gestation) Maternal Toxicity NOEL : 1000 mg/kg/day Clinical Signs: The general condition of females at all dosages remained satisfactory throughout the study and there were no deaths. Salivation after dosing was observed at all dosages. The incidence was dosage related but this finding was not considered to be of toxicological importance. At 1000 mg/kg/day, there were no detectable signs of maternal toxicity; there were no maternal deaths and all females had a live litter at sacrifice. Litter Responses and Fetal Changes Prenatal development NOAEL: 500 mg/kg/day. Although a small number of fetuses with cervical ribs at 1000 mg/kg/day precludes defining this dosage as a NOEL for developmental anomalies, there were no findings at this dosage that were considered indicative of any substantial disturbance of morphological development. Fetal Growth and Development NOEL: 250 mg/kg/day Post-implantation loss was higher in all treated groups compared to the concurrent Control, differences attaining significance at 500 and 1000 mg/kg/day. However values were comparable with recent background control data and it is considered that the test groups were disadvantaged by a particularly high survival rate in the Control. It was concluded that in utero survival had not been adversely affected by treatment since live litter size was unaffected and was similar in all groups.	[4]
Toxicokinetics
Toxicokinetics
Ecotoxicity Data
Algae	EL50 (area under the curve 72h) = 5.2 mg/l EL50 (growth rate 0-72h) = 11 mg/l EL50 (area under the curve 96h) = 5.9 mg/l EL50 (growth rate 0-96h) = 15 mg/l	[4]
Daphnia magna	EL50 (48h) = 6.7 (Daphnia magna) No-observed effect loading rate = 1.0 mg/l (Daphnia magna)	[4]
Other aquatic organisms	-
Fish	LL50 (96h) = 3.9 mg/l (fathead minnow) No-observed effect = 1.5 mg/l (fathead minnow)	[4]
Bacteria	EC50: >10 mg/l, Bacteria (Pseudomonas putida) 10 mg/l was the highest attainable concentration that could be prepared due to the limited solubility to the test material in water and auxiliary solvent and the limitations imposed by the addition of nutrient solutions and bacterial suspension to the test material stock solution.	[5]
Terrestrial organisms	Acute toxicity LC50 > 1000ppm (earthworm, eisenia foetida) NOEL = 1000 ppm	[4]
Sludge	Diethylene glycol dibenzoate had no inhibitory effect on the respiration rate of activated sludge at concentrations up to 100 mg/l.	[5]
Environmental Fate
BCF	An estimated BCF value of 120 was calculated for diethylene glycol dibenzoate, using an estimated log Kow of 3.04 and a recommended regression-derived equation. According to a classification scheme, this BCF value suggests that bioconcentration in aquatic organisms is high.	[3]
Aerobic biodegradation	17% of TCO2 at 2 days 71% of TCO2 at 10 days 93% of TCO2 at 28 days Readily biodegradable	[4]
	Diethylene glycol dibenzoate is considered readily biodegradable in the CO2 evolution test (modified Sturm test). The mean CO2 production by mixtures of diethylene glycol dibenzoate was equivalent to 16% of the theoretical value (TCO2, 106.4 mg CO2) after 2 days of incubation and 63% after 10 days; a mean level of 83% degradation was achieved by the end of the test on Day 29. The mean BOD5 = 0.77 gO2/g Diethylene glycol dibenzoate (34% of it’s ThOD = 2.05 gO2/g) The mean COD = 2.22 gO2/g Diethylene glycol dibenzoate (109% of the ThOD) The BOD5 of Diethylene glycol dibenzoate was 32% of it’s COD. Substances are generally considered readily biodegradable in the Closed Bottle test if the ratio of BOD5:COD or ThOD is >50. Component 1 therefore cannot be considered readily biodegradable in this screening test.	[5]
Anaerobic biodegradation	Diethylene glycol dibenzoate is considered ultimately biodegradable under anaerobic conditions in the biogas production test. The level of anaerobic biodegradation, based on biogas measurements alone, was equivalent to 65% by Day 60 and the total level of biodegradation (dissolved inorganic carbon plus biogas) was calculated to be 70% of the theoretical level.	[5]
Abiotic degradation	The rate constant for the vapour-phase reaction of diethylene glycol dibenzoate with photochemically produced hydroxyl radicals has been estimated as 1.8 x 10-11 cm³/(molecule sec) at 25 ºC using a structure estimation method. This corresponds to an atmospheric half-life of about 20 hours at an atmospheric concentration of 5 x 10+5 hydroxyl radicals per cm³. Diethylene glycol dibenzoate has an estimated base-catalyzed hydrolysis rate of 0.16 l/mol-sec at a pH of 8, which corresponds to a half-life of 49 days at a pH of 8 and 1.3 years at a pH of 7	[3]
Metabolic pathway	-
Mobility	Using a structure estimation method based on molecular connectivity indices, the Koc for diethylene glycol dibenzoate can be estimated to be about 540. According to a recommended classification scheme, this estimated Koc value suggests that diethylene glycol dibenzoate has low mobility in soil.	[3]
Volatilization from water/soil	The Henry's Law constant for diethylene glycol dibenzoate is estimated as 3 x 10-12 atm/m³/mol using a fragment constant estimation method. This value indicates that diethylene glycol dibenzoate will be essentially nonvolatile from water surfaces. Diethylene glycol dibenzoate's estimated values for vapour pressure, 0.09 mm Hg and Henry's Law constant indicate that volatilization from dry and moist soil surfaces should not occur.	[3]
Terrestial fate	Based on a recommended classification scheme, an estimated Koc value of 540, determined from a structure estimation method, indicates that diethylene glycol dibenzoate will have low mobility in soil. Volatilization of diethylene glycol dibenzoate should not be important from moist soil surfaces given an estimated Henry's Law constant of 3 x 10-12 atm/m³/mol, using a recommended regression equation. Volatilization from dry soil surfaces is not expected based on an estimated vapour pressure of 0.09 mm Hg, determined from a fragment constant method. No data are available to determine the rate or importance of biodegradation of diethylene glycol dibenzoate in soil.	[3]
Aquatic fate	Based on a recommended classification scheme, an estimated Koc value of 540, determined from a structure estimation method, indicates that diethylene glycol dibenzoate should adsorb to suspended solids and sediment in the water. Diethylene glycol dibenzoate will be essentially non-volatile from water surfaces based on an estimated Henry's Law constant of 3 x 10-12 atm/m³/mole, developed using a fragment constant estimation method. According to a classification scheme, an estimated BCF value of 120, from an estimated log Kow, suggests that bioconcentration in aquatic organisms is high. Diethylene glycol dibenzoate has an estimated base-catalyzed hydrolysis rate of 0.16 l/mol-sec at a pH of 8, which corresponds to a half-life of 49 days at a pH of 8 and 1.3 years at a pH of 7. Insufficient data are available to determine the rate or importance of biodegradation of diethylene glycol dibenzoate in water.	[3]
Atmospheric fate	According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere, diethylene glycol dibenzoate, which has an estimated vapor pressure of 0.09 mm Hg at 25 ºC, will exist solely as a vapour in the ambient atmosphere. Vapour-phase diethylene glycol dibenzoate is degraded in the atmosphere by reaction with photochemically produced hydroxyl radicals; the half-life for this reaction in air is estimated to be about 20 hours. Particulate-phase diethylene glycol dibenzoate may be physically removed from the air by wet and dry deposition.	[3]
Conclusion
Physical-chemical	-
Emission	-
Exposure	-
Health	-
Environment	-
References
1	ESIS
2	InChem, WHO IPCS
3	HSDB, Toxnet
4	EPA HPV
5	MSDS, Genovique
6	ChemId
7	SRC physprop database

Dipropylene glycol dibenzoate, DGD

Identification of the substance
CAS No.	27138-31-4
EINECS No.	248-258-5	[1]
EINECS Name	oxydipropyl dibenzoate	[1]
Synonyms	Dipropylene glycol dibenzoate DGD
Molecular Formula	C20H22O5	[1]
Structural Formula
Major Uses	-
IUCLID	Is listed as a LPV chemical	[1]
	OECD. Listed as a High Production Volume Chemical.	[4]
EU classification	This substance is not classified in the Annex I of Directive 67/548/EEC as such, but it may be included in one of the group entries.	[1]
	N, R51/53 (self classification)	[4]
Physico-chemical Characteristics
Physical Form	Clear colourless liquid with a mild esterlike odour	[2]
Molecular Weight (g/mole)	342.4	[3]
Melting Point/range (°C)	-30ºC	[7]
Boiling Point/range (°C)	Decomposes above 270ºC without boiling at 762 mm Hg	[2]
	232ºC at 5 mm Hg	[3]
	197 ºC at 1 mm Hg	[7]
Decomposition Temperature (°C)	Decomposes above 270ºC without boiling at 762 mm Hg	[2]
Vapour Pressure (mm Hg at °C)	1.2 x 10-6 mm Hg at 25ºC [1.59 x 10-4 Pa] 1.1 x 10-5 mm Hg at 50ºC [1.46 x 10-3 Pa] 3.8 x 10-4 mm Hg at 100ºC [0.0506 Pa]	[2]
Density (g/cm3 at °C)	1.12	[3]
	1.129 at 25ºC	[7]
Vapour Density (air=1)	11.8	[4]
Henry’s Law constant (atm/m³/mol at °C)	3.8 x 10-8	[2]
	1.38 x 10-8 at 25ºC	[5], [6], [7]
Solubility (mg/l water at °C)	8.69 mg/l at 30ºC, pH = 7.0	[2]
	15 mg/l at 25ºC	[5], [6]
Partition Coefficient (log Pow)	3.9	[2]
	3.88	[5], [6]
pKa	-
Flammability	Combustible. Very slightly to slightly flammable in presence of open flames and sparks.	[4]
Explosivity	Not considered to present risk of explosion	[4]
Oxidising Properties	-
Migration potential in polymer	-
Flash point (ºC)	192	[2]
Viscosity	110 cP at 25ºC	[4]
Atmospheric OH rate constant cm³/(molecule sec)	3.44 x 10-11	[5], [6]
Emission Data
During production	-
Exposure Data
Aquatic environment, incl. sediment	-
Terrestrial environment	-
Sewage treatment plant	-
Working environment	Inhalation and skin contact are expected to be the primary routes of occupational exposure to dipropylene glycol dibenzoate. This material is not expected to cause significant adverse human health effects when used in accordance with good industrial hygiene and safety practices are followed.	[4]
Consumer goods	-
Man exposed from environment	-
”Secondary poisoning”	-
Atmosphere	-
Dermal	-
Toxicological data
Observations in humans	-
Acute toxicity
Oral	LD50 = 3914 mg/kg (rat, combined)	[2]
	LD50 = 5313 mg/kg (rat)	[4]
Dermal	LD50 > 2000 mg/kg (rat)	[2]
	LD50 > 2000 mg/kg (rat)	[4]
Inhalation	LC50 (mist) > 200 mg/l	[4]
Other routes
Skin irritation	A single semi-occlusive application of dipropylene glycol dibenzoate to intact rabbit skin for four hours elicited no dermal irritation.	[2]
Eye irritation	None of the treated animals showed a positive response. No corneal damage or iridial inflammation was observed. Transient hyperemia of blood vessels only was observed in all animals. These reactions had resolved in all instances by one or two days after instillation.	[2]
Irritation of respiratory tract	-
Skin sensitisation	Dipropylene glycol dibenzoate did not produce evidence of skin sensitization (delayed contact hypersensitivity) in any of twenty test animals. Evidence of skin sensitization was produced by hexyl cinnamic aldehyde (HCA) in all ten positive controls thus confirming the sensitivity of the method.	[2]
Subchronic and Chronic Toxicity
Oral	NOAEL = 1000 mg/kg/day (rat, 13 weeks) Dipropylene glycol dibenzoate was administered to rats by dietary admixture to achieve dosages of 0, 250, 1000, 1750 or 2500 mg/kg/day over 13 weeks. Selected Control and Group 5 animals were subsequently maintained off dose for 4 weeks to assess reversibility of any treatment related changes. Dosages of 1000 mg/kg/day or below are considered to represent a No Observable Adverse Effect Level (NOAEL) of Dipropylene glycol dibenzoate in rats by oral administration over 13 weeks. A few minor intergroup differences were noted at 1000 mg/kg/day but were insufficient to be of toxicological importance. Higher dosages of 1750 or 2500 mg/kg/day were tolerated but the adverse effect on bodyweight was more pronounced, there were increases in circulating enzyme activities, low grade hepatocyte hypertrophy and an increased incidence and degree of hemosiderosis in the spleen in one or both sexes. At 2500 mg/kg/day, an increased incidence of minimal epithelial hyperplasia was noted in the caecum. When selected animals previously receiving 2500 mg/kg/day were maintained off dose for 4 weeks, all treatment related effects showed evidence of, or complete, recovery.	[2]
Inhalation	-
Dermal	-
Metabolism	Studies conducted show dipropylene glycol dibenzoate is rapidly metabolized and excreted from the body. It does not accumulate in rats and this behavior is expected in other mammalian systems as well. This conclusion is supported through the test where oral doses of 14C-labeled Dipropylene glycol dibenzoate were rapidly absorbed through the gut in rats. Seventy percent of the administered dose was excreted through the urine within 48 hours as hippuric acid, and about 10% was observed in the feces. The half-life of radiocarbon in the blood was 3 hours and for other organs 2-15 hours.	[2]
Mutagenicity, Genotoxicity and Carcinogenicity
Mutagenicity	S.typhimurium and E.coli (metabolic activator Sprague-Dawley rat liver (S9)) Genotoxic conc: No genotoxic effects observed with or without metabolic activation No evidence of mutagenic activity in this bacterial system.	[2]
	Mouse lymphoma (metabolic activator Sprague-Dawley rat liver (S9)) Genotoxic effects: No effects observed with or without metabolic activation. No evidence of mutagenicity in this in vitro gene mutation assay.	[2]
Chromosome Abnormalities	Chinese hamster lung (metabolic activator Sprague-Dawley rat liver (S9)) Genotoxic effects: No statistically significant increases in the proportion of aberrant cells, when compared to the solvent control, were seen in either the presence or the absence of S9 mix. A small response seen in the first test, with S9 mix, was not reproduced in the repeat test or at the later harvest. This response was not considered to be indicative of clastogenic activity.	[2]
Other Genotoxic Effects	-
Estrogenic activity	Dipropylene glycol dibenzoate did not induce vaginal cornification at doses of 500, 1000, 1500 or 2000 mg/kg/day for 7 days by oral gavage in ovariectomized adult Spraque-Dawley (CD) rats. Dipropylene glycol dibenzoate did not stimulate a uterine weight increase or an increase in the uterine weight to final body weight ratio at doses of 500, 1000, 1500 or 2000 mg/kg/day for 7 days. When compared with the vehicle control (corn oil) and positive control (diethylstilbestrol), these data demonstrate that dipropylene glycol dibenzoate did not exhibit estrogenic activity up to and including the maximally tolerated dose.	[2]
Carcinogenicity	-
Reproductive Toxicity, Embryotoxicity and Teratogenicity
Reproductive Toxicity	Rat (38 weeks duration) The NOEL is 10,000 ppm for F0 and F1 parent animals and the NOAEL for survival and growth of offspring is considered to be 10,000 ppm.	[2]
Teratogenicity	-
Developmental toxicity	Rat (20 days duration from gestation) Maternal Toxicity NOEL : 1000 mg/kg/day Clinical Signs: The general condition of females at all dosages remained satisfactory throughout the study and there were no deaths. Salivation after dosing was observed at all dosages. The incidence was dosage related but this finding was not considered to be of toxicological importance. At 1000 mg/kg/day, there were no detectable signs of maternal toxicity; there were no maternal deaths and all females had a live litter at sacrifice. Litter Responses and Fetal Changes Prenatal development NOAEL: 500 mg/kg/day. A small number of fetuses with cervical ribs at 1000 mg/kg/day precludes defining this dosage as a NOEL for developmental anomalies, in all other respects the NOAEL for pre-natal development is concluded to be 1000 mg/kg/day. Fetal Growth and Development NOEL: 250 mg/kg/day There were no effects of treatment on pre-natal survival or growth. At 1000 mg/kg/day, treatment was associated with a small but definite increase in the number of fetuses with cervical ribs. At 1000 and 500 mg/kg/day, there were a greater number of fetuses with incomplete ossification of the 5th and 6th sternebrae compared with Controls, but this finding was not considered to be of any long term toxicological significance.	[2]
Toxicokinetics
Toxicokinetics
Ecotoxicity Data
Algae	EL50 (area under the curve 72h) = 1.1 mg/l EL50 (growth rate 0-72h) = 4.9 mg/l EL50 (area under the curve 96h) = 0.96 mg/l EL50 (growth rate 0-96h) = 3.6 mg/l NOEL (area under the curve 72h) = 0.22 mg/l NOEL (growth rate 0-72h) = 1.0 mg/l NOEL (area under the curve 96h) = not observed NOEL (growth rate 0-96h) = 0.46 mg/l	[2]
Daphnia magna	EL50 (24h) = 43.2 mg/l (Daphnia magna) EL50 (48h) = 19.31 mg/l (Daphnia magna) No-observed effect loading rate = 2.2 mg/l (Daphnia magna)	[2]
Other aquatic organisms	-
Fish	LC50 (0.25-48h) > 4.9 mg/l (fathead minnow) LC50 (72h) = 4.7 mg/l (fathead minnow) LC50 (96h) = 3.7 mg/l (fathead minnow) No-observed effect concentration = 1.2 mg/l (fathead minnow)	[2]
Bacteria	EC50 > 10 mg/l (pseudomonas putida)	[4]
Terrestrial organisms	Under the conditions of this study, the LC50 of dipropylene glycol dibenzoate to the earthworm was found to be in excess of 1000 ppm. The NOEL was considered to be 1000 ppm.	[2]
Sludge	No inhibitory effect on the respiration rate of activated sludge at concentrations up to 100 mg/l.	[4]
Environmental Fate
BCF	-
Aerobic biodegradation	6% of TCO2 at 2 days 62% of TCO2 at 12 days 85% of TCO2 at 28 days Readily biodegradable	[2]
	The BOD5 of dipropylene glycol dibenzoate was 0.65 gO2/g (30% of its ThOD; 2.15 gO2/g) based on results obtained at a nominal concentration of 2 mg/l. The mean COD of dipropylene glycol dibenzoate (2.33 gO2/g) was 104% of its ThOD which confirmed that the material was completely oxidized in the COD test. The mean BOD5 of dipropylene glycol dibenzoate was 29% of its COD. For screening purposes, substances are generally considered readily biodegradable in this test if the ratio of BOD5:COD or ThOD ≥ 50%. Dipropylene glycol dibenzoate cannot therefore be considered to be readily biodegradable under the conditions of this test. Because this type of BOD test employs both a weak microbial inoculum and a relatively short incubation time, it can be considered to be a particularly stringent test of biodegradability.	[2]
Anaerobic biodegradation	Dipropylene glycol dibenzoate was degraded to 46% after 60 days of incubation and 75% after 120 days of incubation, based on a nominal level of carbon in the culture at the start of the test (12 mgC). At Day 120 of the test, dipropylene glycol dibenzoate was degraded to 90% based on the theoretical carbon level (10 mgC) remaining in cultures following removal of samples for DIC analysis. The precise distribution of dipropylene glycol dibenzoate in test mixtures was not determined in this test so the level of carbon remaining in test mixtures after samples were removed for DIC analysis cannot be accurately determined. However, since the octanol:water partition coefficient for dipropylene glycol dibenzoate is relatively high (log Pow 3.9), it is likely that the material will adsorb onto sewage solids. Although the level of biodegradation calculated using the nominal level of carbon at the start of the test (12 mgC) gives the worst case estimate, it is likely to be the most accurate. Substances are considered to be ultimately degraded under anaerobic conditions in this test if the level of degradation is equal to or greater than 60%. Dipropylene glycol dibenzoate can therefore be considered ultimately biodegradable under anaerobic conditions.	[2]
Abiotic biodegradation	-
Metabolic pathway	-
Mobility	-
Photodegradation		[2]
Stability in water	-
Transport (fugacity)	-
Conclusion
Physical-chemical	-
Emission	-
Exposure	-
Health	-
Environment	-
References
1	ESIS
2	EPA HPV challenge programme
3	Sigma Aldrich MSDS
4	Genovique MSDS for Benzoflex 9-88
5	ChemID
6	SRC PhysProp database
7	MITI

Di-isononyl-cyclohexane-1,2dicarboxylate, DINCH

Identification of the substance
CAS No.	166412-78-8 (EU) 474919-59-0 (USA and Canada)	[4]
EINECS No.	431-890-2	[1]
EINECS Name	1,2-Cyclohexanedicarboxylic acid, 1,2-diisononyl ester	[2]
Synonyms	Di-isononyl-cyclohexane-1,2-dicarboxylate DINCH Hexamoll DINCH 1,2-Cyclohexanedicarboxylic acid, diisononyl ester (9CI) 1,2-Cyclohexanedicarboxylic acid, diisononyl ester, branched and linear
Molecular Formula	C26H48O4
Structural Formula
Major Uses	The major applications for the notified chemical will use it as a plasticiser and impact modifier in food packaging, but also in general applications such as wire and cable, automotive, plastisols and other similar applications.	[2]
IUCLID	-
EU classification	-
Physico-chemical Characteristics
Physical Form	Clear colourless liquid at 20ºC and 101.3 kPa Almost odourless	[2], [3]
Molecular Weight (g/mole)	424.6	[2]
Melting Point/range (°C)	No freezing point Glass point < -90ºC Pour point = -54ºC	[2]
Boiling Point/range (°C)	> 351ºC at 101.3 kPa	[2]
	240 – 250ºC at 7 mbar	[3]
Decomposition Temperature (°C)	> 351ºC at 101.3 kPa, decomposes before boiling	[2]
Vapour Pressure (mm Hg at °C)	2.2 x 10-8 kPa at 25ºC [2.2 x 10-5 Pa, 1.65 x 10-7 mmgHg] 8.9 x 10-7 kPa at 50ºC [8.9 x 10-4 Pa, 6.67 x 10-6 mmgHg]	[2]
Density (g/cm3 at °C)	0.947 at 20ºC	[2]
Vapour Density (air=1)	-
Henry’s Law constant (atm/m³/mol at °C)	-
Solubility (mg/l water at °C)	< 0.00002 g/l at 25ºC [< 0.02 mg/l]	[2]
Partition Coefficient (log Pow)	> 6.2 at 25ºC	[2]
pKa	-
Flammability	Not highly flammable	[2]
Explosivity	Not explosive	[2]
Oxidising Properties	-
Migration potential in polymer	-
Viscosity	44-60 mPa.s at 20ºC	[2]
Absorption/Desorption (log Koc)	> 5.6 at 23ºC	[2]
log Kow	10	[4]
Autoignition temperature	330ºC	[2], [3]
Flash point	224ºC	[2], [3]
Emission Data
During production	-
Exposure Data
Aquatic environment, incl. sediment	-
Terrestrial environment	-
Sewage treatment plant	-
Working environment
	Transport and storage The notified chemical will be transported by road to a warehouse and then to the compounding facility. Exposure of receivers and transport personnel should only occur in the event of an accidental spillage.	[2]
	Compounding Incidental skin contact with the notified chemical may occur when the storemen insert the drum lance into the 200 L drum, or during connection of an IBC or isotank to the weighing vessel. Inhalation exposure to vapours may also occur during the transfer process. After mixing, intermittent skin contact may occur during the packaging process, from powdered blend or liquid plastisol. Quality control samples may also be taken at this stage, as technical personnel will make up small-scale compounds by hand in the laboratory. During the subsequent compounding of dry blend into pellets, closed systems are used, and any exposure will be incidental. However, manual operations during this process may include opening of packages, connection/insertion of lines/hoses, pumping liquid products, and eventual removal of connections and closing the containers. In addition, maintenance workers may experience skin contact with the notified chemical. For the specific formulation sites in Australia, a pproximately one third of the production time for the operators will be dedicated to running compound. During production runs (which can be up to 5 days long), the operators will work two 12-hour shifts, 5 days per week, and 48 weeks per year. Workers will prepare approximately 8 batches per day. Given the time that it takes to connect up and transfer product, the estimated period of direct contact with the notified chemical is less than 30 minutes per day for one person per shift. Local exhaust ventilation will be employed at all workplace areas where natural ventilation is considered inadequate. Workers, particularly for those operators involved in any open transfer operations, wear personal protective equipment (PPE) including overalls, safety glasses/goggles and face splash shields, protective gloves, and are assumed to operate using appropriateindustrial hygiene practices.	[2]
	Product manufacture Exposure to the notified chemical may occur during the processing of PVC compound or plastisol to manufacture the end-use product. Once compounded with PVC, the notified chemical is bound within the PVC matrix and exposure is unlikely. However, during product manufacture by processes such as extrusion, calendering and injection moulding, the elevated temperatures required may result in inhalation exposure to the notified chemical, whether from vapours or aerosols. The methods for product manufacture from plastisols include spread coating, under-body coating, sealing, rotational coating, dipping and slush moulding. Although the processes are largely automated and enclosed, incidental skin contact with the notified chemical may occur during transfer of plastisol from drums to the moulding equipment. Workers are expected to wear PPE including overalls, gloves and eye protection.	[2]
	End-use of products Under normal circumstances, dermal exposure to the notified chemical is not expected during handling of PVC products, as it is expected to be physically bound within the PVC matrix. Exudation may occur during any heating of plastics, leading to possible skin and inhalation exposure to low levels of the notified chemical.	[2]
	Occupational exposure estimation For dermal exposure of workers involved in handling of the notified chemical during compounding and/or product manufacture, assuming non-dispersive use with some intermittent direct contact, EASE exposure modelling estimates the dermal exposure to the notified chemical to be 0-0.1 mg/cm²/day (EC, 2003). However, the use of EASE for accurately predicting dermal exposures is thought to be limited in accuracy (EC, 2003). The RISKOFDERM project, based on measurements of industrial exposures, describes exposure levels to the hands fo r the addition of liquids into "large containers (or mixers) with large amounts (many litres) of liquids" (Marquart et al, 2006). In this study, a typical case exposure was described as 0.5 mg/cm²/scenario, though a reasonable worst-case exposure was described as 14 mg/cm²/scenario. Therefore, based on a reasonable exposure frequency of once daily and a whole-hand exposure (420 cm²) to a 60 kg adult, a typical dermal exposure of 3.5 mg/kg bw/day is assumed. Worst-case, infrequent (whole-hand) exposures may be as high as 98 mg/kg bw/scenario. Assuming a closed system with LEV, a highest-probable process temperature of 220ºC (and excluding the possibility of aerosol formation), EASE estimates that the gas/vapour exposure to the notified chemical is likely to be 0-1.8 mg/m³ (0-0.1 ppm) (EC, 2003). The same value is estimated for an identical system at 25ºC. Therefore as a worst-case estimate, a 60 kg adult male worker exposed to vapours with an inhalation rate of 25.5 m³/12-hour shift during medium activity (EC, 2003), might experience inhalation exposure to the no tified chemical of 0-0.77 mg/kg bw/day.	[2]
	Therefore, excluding oral exposure and assuming 10% dermal and 100% inhalation absorption (EC, 2003), the typical exposure during handling of the notified chemical is estimated to be 0.35-1.12 mg/kg bw/day.	[2]
Consumer goods	The notified chemical has undergone assessment by the European Food Safety Authority in September 2006 (EFSA, 2006). For this assessment, the specific migration of the notified chemical was measured using various food simulants and representative foodstuffs, under different storage conditions. The specific migration of 10-17.8% notified chemical in plasticised PVC cling film into food simulants and foodstuffs was determined using a validated Gas Chromatography/Mass Spectrometry (GC/MS) method (Otter, 2007):	[2]
	The notified chemical was found to migrate into foods with high fat content (e.g. .29 mg/dm² into sunflower oil, and .27.5 mg/dm² into high fat cheese). The migration of the notified chemical into food like fresh meat and low fat cheese was lower than that of foods containing higher fat levels (<2.4 mg/dm²). The level of notified chemical in fresh meat at equilibrium was found to be proportional to the starting concentration in the cling film and relative to the fat content of the foods. In fatty foods, migration to equilibrium was achieved after 6 hours of contact. Likewise, extraction studies from bottle closures using isooctane (in which the notified chemical is very soluble) show that it is able to extract an equilibrium concentration of the notified chemical after 5.3 hours. For the use of the notified chemical in bottle sealing gaskets, artificial wine corks and beverage tubes, migration of the notified chemical into mineral water, grapefruit juice, soft drink or 15% ethanol was found to be very low (generally less than 0.11 mg/L, its solubility in 15% ethanol). This level of migration of the notified chemical is expected to apply for all aqueous foods (except alcoholic drinks with high ethanol content) as the low aqueous solubility of the notified chemical would limit its migration. Migration of the notified chemical from polystyrene (at the proposed use concentration) is expected to be lower than that from PVC. A test study using notified chemical-containing polystyrene sticks showed no migration of the notified chemical into olive oil or aqueous 10% ethanol (after 10 days at 40ºC) above the detection limit of the analytical method (unpublished study provided by the notifier). Very low levels of migration of the notified chemical from polystyrene into aqueous 50% ethanol were observed. For conveyor belts, migration into solid or semi-solid foods is expected to be limited by contact area and short contact times. Computer modelling of fatty food with .30 minutes contact time on a conveyor belt containing 12% notified chemical estimates specific migration rates of 12.4 mg/dm² at 20ºC and 6.6 mg/dm² at 10ºC (Otter, 2007). Therefore, assuming that migration into most foods will be considerably less than migration into oil, and that only the bottom of food is in contact with the conveyor belt (1 dm²/kg), the migration of the notified chemical is expected to be <5 mg/kg food for 0.30 minutes contact time.	[2]
Man exposed from environment	-
”Secondary poisoning”	-
Atmosphere	-
Dermal	Members of the public are likely to make limited dermal contact with food packaging, wires, cables and/or automotive parts containing the notified chemical. Significant exposure to the notified chemical in plastic products as a result of casual contact during handling is not expected, as it is expected to be sufficiently bound within the plastic matrix. However, as the notified chemical will not be chemically bound, it may be released from products in low levels over time (e.g. volatilisation from car upholstery). The expected dermal exposure from prolonged contact with plastics containing the notified chemical cannot be accurately estimated, but may be significant as the notified chemical may partition from the plastic into the skin over time.
Toxicological data
Observations in humans	-
Acute toxicity
Oral	LD50 > 5000 mg/kg (rat)	[2]
Dermal	LD50 > 2000 mg/kg (rat)	[2]
Inhalation	-
Other routes	-
Skin irritation	Slightly irritating (rabbit)	[2]
Eye irritation	Not irritating (rabbit)	[2]
Irritation of respiratory tract	-
Skin sensitisation	No evidence of skin sensitisation	[2]
Subchronic and Chronic Toxicity
Oral	Rat, 28-day oral repeat dose NOAEL = 318 mg/kg (male) NOAEL = 342 mg/kg (female)	[2]
	Rat, 90-day oral repeat dose NOAEL = 107.1 mg/kg (male) NOAEL = 389.4 mg/kg (female)	[2]
	Rat, 2-year chronic toxicity/carcinogenicity NOAEL = 40 mg/kg (male) NOAEL = 200 mg/kg (female)	[2]
Inhalation	-
Dermal	-
Metabolism	After oral administration DINCH showed rapid but saturable absorption and extensive elimination 24 hours after dosing approximately 80% of the radioactivity is excreted, after 48 hours more than 90 % is excreted via urine and mainly via feces.Based on the amounts of radioactivity excreted in the bile and urine, the bioavailability of 14C-1,2-yclohexanedicarboxylic acid di(isononyl)ester is estimated to be 5-6% at the high dose and 40-49 % at the low dose. There is no indication of bioaccumulation. The characterisation of metabolites after oral and intravenous administration of DINCH indicates two main pathways: the partial hydrolysis of DINCH to the mono-isonyl ester followed by conjugation to glucuronic acid, which is the most ab Undant metabolite in bile, or the hydrolysis of the remaining ester bond to yield free cyclohexane dicarboxylic acid, the predominant urinary metabolite.	[4]
Mutagenicity, Genotoxicity and Carcinogenicity
Mutagenicity	S.typhimurium and E.coli (metabolic activator Aroclor 1254-induced rat liver (S9)) Not mutagenic to bacteria under the conditions of the test.	[2]
	Chinese hamster (CHO cells) (metabolic activator Aroclor 1254-induced rat liver (S9)) Not observed to induce mutations in CHO cells treated in vitro under the conditions of the test.	[2]
Chromosome Abnormalities	Chinese hamster (V79 cells) (Phenobabital/3-naphthoflavone-induced rat liver S9 mix) Not clastogenic to V79 cells treated in vitro under the conditions of the test.	[2]
	Mouse Not found to be clastogenic or aneuploidogenic under the conditions of this in vivo mouse micronucleus test.
Other Genotoxic Effects	-
Carcinogenicity	Rat, 2-year chronic toxicity/carcinogenicity NOAEL = 40 mg/kg (male) NOAEL = 200 mg/kg (female)	[2]
Reproductive Toxicity, Embryotoxicity and Teratogenicity
Reproductive Toxicity	Rat, two-generation study (37 weeks) Under the conditions of this two-generation reproduction study, the NOAEL for fertility and reproductive performance is 1000 mg/kg bw/day for F0 and F1 generation rats of both genders. The NOAEL for general toxicity is 1000 mg/kg bw/day (F0 rats of both genders) and 100 mg/kg bw/day for the F1 male and female rats (based on tubular vacuolisation and flaky thyroid follicular colloid). The NOAEL for developmental toxicity (growth and development of offspring) was 1000 mg/kg bw/day for the F1 and F2 pups.	[2]
Teratogenicity	-
Developmental toxicity	Rabbit (exposure day 6 to day 29 post insemination) NOAEL = 1000 mg/kg, based on maternal and prenatal developmental toxicity.	[2]
	Rat (exposure day 6 to day 19 post coitum) NOAEL = 1200 mg/kg, based on maternal and prenatal developmental toxicity.	[2]
Pre-/Postnatal developmental toxicity	Rat (exposure day 6 to day 20 post partum) Based on the conditions of this study, the No Observed Adverse Effect Level (NOAEL) for reproductive performance and systemic toxicity of the parental female rats is 1000 mg/kg bw/day. The NOAEL for developmental toxicity (based on the growth and development of the offspring, including sexual organ morphology and sexual maturation) is also 1000 mg/kg bw/day for F1 progeny.	[2]
Toxicokinetics
Toxicokinetics	Rat, toxicokinetics and metabolism Distribution to all organs and tissues was observed after rapid absorption. The oral bioavailability was calculated to be ~5-6% of a high dose and ~40-49% of a low dose, indicating saturation of gastrointestinal absorption. Accumulation was not observed in rats, and excretion was rapid, mainly via the faeces. Metabolism to several major metabolites: cyclohexanedicarboxylic acid (urine), monoisononyl cyclohexanedicarboxylate (faeces) & the glucuronide of monoisononyl cyclohexanedicarboxylate (bile)	[2]
Ecotoxicity Data
Algae	Scenedesmus subspicatus Biomass EC50 > 100 mg/l WAF (72h) NOEC ≥ 100 mg/l WAF Growth EC50 > 100 mg/l WAF (72h) NOEC ≥ 100 mg/l WAF	[2]
Daphnia magna (acute)	LC50 > 100 mg/l WAF (48h, daphnia magna) ("Water Accommodated Fraction" (WAF) NOEC = 100 mg/l WAF (48h)	[2]
Daphnia magna (chronic)	Daphnia magna (21 days) NOEC ≥ 0.021 mg/l LOEC ≥ 0.021 mg/l LCD ≥ 0.021 mg/l	[2]
Other aquatic organisms	-
Fish	LC50 > 100 mg/l (96h, zebra fish) NOEC = 100 mg/l (96h)	[2]
Bacteria	-
Terrestrial organisms	LC0 > 1000 mg/kg (earth worm, 14 day) LC50 > 1000 mg/kg (earth worm, 14 day) LC100 > 1000 mg/kg (earth worm, 14 day)
Sludge	EC50 >1000 mg/L (nominal) The oxygen concentration decreased more significantly for the test substance than for the blank controls. The oxygen consumption rate did not differ between the test substance and the controls. The oxygen consumption rate of the reference substance is significantly lower than both the rate of the test substance and the blank samples and the reference met the validity criteria (EC50 = 6.5 mg/L).	[2]
Higher plants	The EC50 test results, relating to dry mass of the soil, for all three species (Avena sativa, Brassica napus and Vicia sativa) are as follows: EC50 (emergence rate) >1000 mg/kg (nominal) EC50 (dry matter) >1000 mg/kg (nominal) EC50 (fresh matter) >1000 mg/kg (nominal) EC50 (shoot length) >1000 mg/kg (nominal) The NOEC/LOEC tests results relating to the dry mass of the soil for all the three species (Avena sativa, Brassica napus and Vicia sativa) are as follows: NOEC/LOEC (emergence rate) .1000 mg/kg (nominal) NOEC/LOEC (dry matter) .1000 mg/kg (nominal) NOEC/LOEC (fresh matter) .1000 mg/kg (nominal) NOEC/LOEC (shoot length) .1000 mg/kg (nominal)	[2]
Environmental Fate
BCF	BCF = 189.3 DT50 = 0.5 (low conc) DT50 = 0.6 (high conc) Not likely to bioaccumulate	[2]
Aerobic biodegradation	BILLEDE The substance is not readily biodegradable.	[2]
Anaerobic biodegradation	-
Metabolic pathway	-
Mobility	-
Conclusion
Physical-chemical	-
Emission	-
Exposure	-
Health	-
Environment	-
References
1	ESIS
2	NICNAS
3	BASF MSDS
4	SCENIHR

Di (2-ethyl-hexyl) terephthalate, DEHT, DOTP

Identification of the substance
CAS No.	6422-86-2
EINECS No.	229-176-9	[1]
EINECS Name	bis(2-ethylhexyl) terephthalate	[1]
Synonyms	Di-(2-ethyl-hexyl)-terephthalate DEHT DOTP
Molecular Formula	C24H38O4	[1]
Structural Formula
Major Uses	Softeners	[2]
IUCLID	Not listed	[1]
EU classification	This substance is not classified in the Annex I of Directive 67/548/EEC as such, but it may be included in one of the group entries.	[1]
Physico-chemical Characteristics
Physical Form	Liquid	[2]
	Colourless, mobile and highly volatile liquid with a pleasant odour.	[3]
Molecular Weight (g/mole)	390.557	[3]
Melting Point/range (°C)	-48ºC	[2], [3]
Boiling Point/range (°C)	383ºC at 1015 hPa	[2], [3]
	400ºC	[7]
Decomposition Temperature (°C)	-
Vapour Pressure (mm Hg at °C)	0.0000285 hPa at 25ºC [2.85 x 10-3 Pa, 2.13 x 10-5 mmgHg] 1013 hPa at 398ºC [1.013 x 105 Pa, 757.8 mmgHg]	[2]
	2.14 x 10-5 mm Hg at 25ºC [2.85 x 10-3 Pa]
	1.33 mbar at 217ºC [133 Pa , 0.99 mmHg] 5.56 x 10-10 mbar at 25ºC [5.56 x 10-8 Pa , 4.17 x 10-10 mmHg]	[7]
Density (g/cm3 at °C)	0.984 at 20ºC	[2]
	0.9825 at 20ºC	[3]
Vapour Density (air=1)	13.5	[3]
Henry’s Law constant (atm/m³/mol at °C)	1.18 x 10-5	[2]
	1.02 x 10-5  25ºC	[3]
Solubility (mg/l water at °C)	0.4µg/l at 22.5ºC [GLP study from 2002] The aqueous solubility of DOTP has been recently determined to be 0.0004 mg/L (0.4 ppb) at 22.5 C using the slow-stir method. Results of earlier solubility studies have been reported that are significantly higher: values of 0.35 mg/L in well water, 0.61 mg/L in sea-water, and 1.5 mg/L in de-ionized water, all at 25 C. However, these earlier studies were performed using the shake-flask technique, which is no longer considered appropriate for oily hydrophobic substances such as DOTP.	[2]
Partition Coefficient (log Pow)	8.39	[2]
pKa	-
Flammability	-
Explosivity	-
Oxidising Properties	-
Migration potential in polymer	-
Flash point	238ºC open cup	[2]
Auto flammability	399ºC	[2]
Atmospheric OH rate constant cm³/(molecule sec)	21.9554 x 10-12	[2]
	2.2 x 10-11 at 25ºC	[4]
Log Kow	8.39	[3]
Emission Data
During production	Minimal potential for air pollution. Material has a very low volatility.	[2]
Exposure Data
Aquatic environment, incl. sediment	Bis(2-ethylhexyl) terephthalate's production and subsequent use as a plasticizer may result in its release to the environment through various waste streams	[3]
Terrestrial environment	-
Sewage treatment plant	-
Working environment	Production uses a closed system. Exposure could occur when chemical is put into drums or during quality control.	[2]
	Occupational exposure to bis(2-ethylhexyl) terephthalate may occur through inhalation of aerosols and dermal contact with this compound at workplaces where bis(2-ethylhexyl) terephthalate is produced or used. Use data indicate that the general population may be exposed to bis(2-ethylhexyl) terephthalate via dermal contact from products containing this compound.	[3]
Consumer goods	Minimal consumer exposure expected based on limited use in consumer products and low migration of the substance out of the polymer matrix in it's major use as a plasticizer.	[2]
Man exposed from environment	-
”Secondary poisoning”	-
Atmosphere	-
Dermal	-
Toxicological data
Observations in humans	Primary dermal irritation There was one adverse event reported during the course of the study that was not related to test-substance exposure. Overall irritation scores ranged from 0.00 to 0.11. Since the irritation did not occur in a concentration-dependent manner, it was not considered to be related to test substance exposure.	[2]
	Skin sensitization Under the conditions of this study, DOTP was found to be non-irritating and did not elicit evidence of sensitization. There were nine adverse events which occurred during the study, one of them severe. One of the events (soreness at the test site location) was clearly related to test substance exposure. However, this reaction was to another material being tested, not DOTP. Another event, (papular rash) was possibly related to test substance exposure. The rest of the events were unrelated to test substance exposure. Slight erythema was observed for one to seven subjects at any given time during the induction phase of the study, and for only one subject during the challenge phase of the study.	[2]
Acute toxicity
Oral	LC50 > 5000 mg/kg (rat, combined)	[2]
	LC50 > 3200 mg/kg (rat, male)	[2]
	LC50 > 3200 mg/kg (mouse, male)	[2]
	LDL0 = 20,000 mg/kg (mouse)	[5]
Dermal	LC50 > 19670 mg/kg (guinea pig, male)	[2]
Inhalation	Acute Exposure/ No deaths occured following inhalation exposure of mice for 4 hr to "saturated" vapors; however, mucosal irritation, loss of coordination and decreased mobility were noted. Recovery occured in 24 hours.	[3]
Other routes	-
Skin irritation	Slightly irritating (guinea pig, 24h)	[2]
	Not irritating (human)	[7]
Eye irritation	Slightly irritating (rabbit)	[2]
Irritation of respiratory tract	-
Skin sensitisation	Not sensitizing (guinea pig)	[2]
Subchronic and Chronic Toxicity
Oral	Rat, 90-day repeat dose NOEL = 277 mg/kg (male) NOEL = 309 mg/kg (female)	[2], [3]
	Di(2-ethylhexyl) terphthalate was evaluated for subchronic toxicity in Charles River rats (17-20/sex/group) fed diets containing concentrations of 0, 0.1, 0.5, or 1.0% for 90 days. There were statistically significant differences between treated and control animals in the following: decreased mean corpuscular hemoglobin (1% animals, 0.5% females), mean corpuscular volume (0.5% and 1% animals), hemoglobin (1% and 0.1% males), hematocrit (1% males), and serum glucose (0.1% females), and increased relative liver weight (1% animals). Variations in red blood cell morphology were observed in all groups (and therefore not considered to be treatment-related) including microcytosis, anisocytosis, poikilocytosis, and spherocytosis. No treatment-related gross or microscopic abnormalities were observed. There were no consistent, significant, exposure-related differences between treated and control animals in the following: mortality, body weight gain, food consumption, clinical signs of toxicity, clinical chemistry (except serum glucose), and absolute and relative organs weights (except relative liver weight)	[3]
	Rat, 21-day repeat dose NOEL = 505 mg/kg (male) NOEL = 487 mg/kg (female)	[2]
	Rat, 14-day repeat dose NOEL = 885 mg/kg	[2]
Inhalation	Rat, 10-day exposure 6h per day NOEL = 46.3 mg/m³	[2]
Dermal	-
Metabolism	Rat Approximately 25% of DEHT was hydrolyzed to 2EH- after about 10 minutes. The rest of the compound remained unchanged, and there was no evidence to suggest that 2EH was metabolized further. After 30 minutes, the stoichiometry indicated 2 moles of 2EH had been formed per mole of DEHT, indicating complete hydrolysis. The half-life of DEHT was calculated to be 53.3 minutes.	[2]
	Rat The results obtained with DEHT are in contrast to DEHP, which is hydrolyzed to 2-ethylhexanol and the monoester MEHP. The mean total recovery of 14C was 93.0 +/- 2.2%. Most of the radioactivity was eliminated in the feces (56.5 +/- 12.1%) and urine (31.9 +/- 10.9%), with smaller amounts in expired air (3.6 +/- 0.9%). Approximately 1.4 +/- 0.6% of the dose remained in the carcass. Of the approximately one half of the material that was absorbed, 73% was excreted in the urine and 8.3% was completely metabolized to 14CO2. About half (50.5%)of the total dose (77% of the absorbed dose) was detected as unlabelled terephthalic acid (TPA) in the urine, indicating that complete hydrolysis of the diester had taken place. Almost one-third of the radioactivity in the urine (10 % of the dose) was present as glucuronide and sulphate conjugates. Several oxidation products of mono(2-ethylhexyl) phthalate (MEHT) and 2-ethylhexanol (2-EH)were identified as minor components. Between 90-95 % of the total activity in the feces was unchanged [14C]DEHT (36.6% of the total dose). MEHT (2.5% of total dose) and the glucuronide conjugate of 2-ethyl5-hydroxyhexanoic acid were also identified. Several other minor uncharacterized radiolabelled metabolites were detected that were more polar than DEHT. The mean total amount of material recovered in the urine (as unlabeled TPA) and fecal fractions (as unmetabolized DEHT) was 87.1%, indicating that a major portion of the dose passed directly through the GI tract without hydrolysis or was completely hydrolyzed to TPA and 2-EH before or after absorption. The rates of excretion of radioactivity in urine and feces revealed that more than 95 and 99% of the total radioactivity was excreted by 24 and 48 hours, respectively. The time course for expired 14CO2 was complex, with peaks at 1.3, 2.8, and 5.0 hours after dosing. Approximately 68% of the total radioactivity in expired air was eliminated after 4 hours and the remaining 32% was eliminated after 40 hours. The excretion of radioactivity in the feces, urine and expired air from animals given food 4 hours after dosing was comparable to the levels seen for animals given food immediately after dosing.	[2], [3]
Absorption	Rats readily excreted (14)C EHT given in a single dose at 100 mg/kg. 57.9%, 28.6%, and 3.6% of the (14)C was recovered in the feces, urine an expired air, respectively, within 144 hr after admin. Only 2.1% remained in the carcass	[3]
Absorption, distribution and excretion	The hydrolysis of di(2-ethylhexyl) terephthalate and di(2-ethylhexyl) phthalate were studied using rat gut homogenate fractions in vitro. Both isomers were hydrolysed by the intestinal fraction; however di(2-ethylhexyl) phthalate was hydrolysed to 2-ethylhexanol and mono(2-ethylhexyl) phthalate in about equal proportions whereas di(2-ethylhexyl) terephthalate was hydrolysed to 2-ethylhexanol and terephthalic acid. The half-lives for disappearance of the diesters were determined to be 12.6 min for di-(2-ethylhexyl) phthalate and 53.3 min for di(2-ethylhexyl) terephthalate. 2. The absorption and metabolism of di(2-ethylhexyl) terephthalate were studied by administering (hexyl-(14)C)di(2-ethylhexyl) terephthalate (in corn oil) by oral gavage at a dose level of 100 mg/kg to 10 adult male Sprague Dawley rats. Urine feces and expired air were collected for 144 hr and analysed for thepresence of radioactivity and feces and urine were analysed for unlabelled metabolites. 3. Radioactivity was eliminated in feces (56.5 +/- 12.1% of dose) primarily as unchanged di(2-ethylhexyl) terephthalate, small amounts of mono(2-ethylhexyl) phthalate and polar metabolites; excreted in urine (31.9 +/- 10.9% of dose) principally as mono(2-ethylhexyl) phthalate and metabolic products of 2-ethylhexanol; and expired as (14)C02 (3.6 +/-0.9% of dose). Less than 2% of the administered radioactivity was found in the carcass. Small amounts of (14)C were found in the tissues with the highest amounts found in liver and fat. 4. Metabolites identified in urine included terephthalic acid (equivalent to 51% of dose), oxidized metabolites of 2-ethylhexanol and mono(2-ethylhexyl) phthalate, and glucuronic and sulfuric acid conjugates (equivalent to about 10% of dose). 5. These findings indicate that di(2-ethylhexyl) terephthalate was hydrolysed more extensively than di(2-ethylhexyl) phthalate and consequently the urinary metabolite profiles for these two isomeric plasticizers were very different. The hydrolysis and metabolism of di(2-ethylhexyl) terephthalate were found to be similar to those of di(2-ethylhexyl) adipate in that hydrolysis of both ester bonds occurs.	[3]
Mutagenicity, Genotoxicity and Carcinogenicity
Mutagenicity	Salmonella typhimurium (metabolic activator induced rat liver (S9)) There was no increase in the number of revertants for any of the five strains either in the presence or absence of metabolic activation up to dose levels of 10,000 µg/plate.	[2], [3], [6]
	Chinese hamster (CHO cells) (metabolic activator induced rat liver (S9)) In the cultures treated with DOTP, no statistically significant increases in aberrations were observed at any dose level.	[2]
	Chinese hamster (CHO cells) (metabolic activator induced rat liver (S9)) DOTP is negative in the CHO/HGPRT mammalian cell mutation assay at dose levels up to 20 nl/ml (the limit of the test).	[2]
	Salmonella typhimurium (metabolic activator induced rat liver (S9) No mutagenic activity was detected with unmetabolized DEHT, and there was no evidence that mutagenic substances were excreted in the urine from rats dosed with DEHT.	[2], [3]
Chromosome Abnormalities	-
Other Genotoxic Effects	-
Estrogenic activity	NOAEL = 2000 mg/kg (rat, female)	[2]
Carcinogenicity	Bis(2-ethylhexyl) terephthalate was evaluated for combined chronic toxicity and carcinogenicity. The test substance was administered in the diets of male and female Fischer-344 inbred rats at concentrations of 20, 142, and 1000 mg/kg/day. Clinical evaluations revealed no treatment-related signs, however, eye opacities (cataracts) occurred frequently in all groups. At 1000 mg/kg/day, body weights and female liver weights were reduced. There were no consistent reductions in food consumption. There were no treatment-related effects evident from the gross and histopathologic examinations conducted at 6 and 12 months. At 18 months, two basic lesions of the females in the 1000 mg/kg/day level appear to be associated with treatment. These were hyperplasia and/or transitional cell adenomas of the urinary bladder and adenomas or adenocarcinomas of the uterus.	[3]
Reproductive Toxicity, Embryotoxicity and Teratogenicity
Reproductive Toxicity	Rat, two-generation study NOAEL = 3000 ppm (Parental) NOAEL = 3000 ppm (F1 offspring) NOAEL = 3000 ppm (F2 offspring)	[2]
Teratogenicity	Rat (exposure day 0 to 20 gestation) NOEL = 6000 ppm (maternal) NOEL = 10000 ppm (teratogenicity)	[2]
	Rat (exposure day 14 to postnatal day 3) NOEL = 750 mg/kg (maternal) NOEL = 750 mg/kg (teratogenicity)	[2]
Other Toxicity Studies	Skin absorption (in vitro) Dematomed human cadaver skin specimen The absorption rate of DEHT through dermatomed human skin was found to be 0.103 +/- 0.052 µg/cm²/hr. According to the criteria set forth by Marzulli (1969), DEHT would be considered an "extremely slow" penetrant relative to other chemical species. The mean damage ratio for skin treated with DEHT was determined to be 1.14 +/- 0.23. This value is within the range of damage ratios for skin exposed to physiological saline (Dugard et al 1884). Therefore, under the conditions of this study, DEHT did not cause significant damage to the skin.	[2]
	Male development NOEL > 750 mg/kg No effect on male organ development	[7]
	Uterotrophic assay NOEL > 2,000 mg/kg No estrogenic activity Results of several robust studies following established guidelines to assess both reproductive and developmental toxicity potential have been conducted on Eastman 168 Plasticizer. The results of these studies indicate there is no evidence of such toxicities when tested in the diet at very high levels 1.0% (rats) and 0.7% (mice). Experimental studies have been conducted to evaluate the potential of DEHT to alter normal postnatal development in males and act as an estrogen agonist in females (uterotrophic assay). DEHT had no “endocrine”-like effects in either study.	[7]
Toxicokinetics
Toxicokinetics	-
Ecotoxicity Data
Algae	EC50 > 0.86 mg/l (selenastrum capricornutum, 3h) NOEC ≥ 0.86 mg/l (selenastrum capricornutum, 3h)	[2]
Daphnia magna (acute)	EC50 > 1.4 µg/l (daphnia magna, 48h) NOEC ≥ 1.4 µg/l (daphnia magna, 48h)	[2]
	EC50 > 984 mg/l (planorid snail, 96h) NOEC ≥ 984 mg/l (planorid snail, 96h)	[2]
	EC50 > 624 µg/l (eastern oyster, 96h) NOEC ≥ 624 µg/l (eastern oyster, 96h)	[2]
Daphnia magna(chronic)	EC50 > 0.76 µg/l (daphnia magna, 21 day) NOEC ≥ 0.76 µg/l (daphnia magna, 21 day) LOEC > 0.76 µg/l (daphnia magna, 21 day) MATC > 0.76 µg/l (daphnia magna, 21 day)	[2]
Other aquatic organisms	-
Fish (acute)	LC50 > 984 mg/l (fresh water fish, 96h) NOEC ≥ 984 mg/l (fresh water fish, 96h)	[2]
	EC50 > 1000µg/l (Fathead minnow, 96h) NOEC ≥ 1000µg/l (Fathead minnow, 96h)	[2]
	LC50 > 0.25 mg/l (Salmo gairdneri, 7 day) NOEC ≥ 0.25 mg/l (Salmo gairdneri, 7 day)	[2]
Fish (chronic)	LLC ≥ 0.28 mg/l (salmo gairdneri, 71 days) NOEC ≥ 0.28 mg/l (salmo gairdneri, 71 days)	[2]
Bacteria	-
Terrestrial organisms	-
Sludge	EC50 > 10 mg/l (3h) NOEC ≥ 10 mg/l (3h)	[2]
Terrestrial plants	EC50 > 1400 µg/l (lolium perenne, 14 days) NOEC ≥ 1400 µg/l (lolium perenne, 14 days)	[2]
	EC50 > 1500 µg/l (Williams 82 soybean, 14 days) NOEC ≥ 1500 µg/l (Williams 82 soybean, 14 days)	[2]
	EC50 > 1400 µg/l (Raphanus sativus, 14 days) NOEC ≥ 1400 µg/l (Raphanus sativus, 14 days)	[2]
Environmental Fate
BCF	BCF = 393	[2]
	An estimated BCF of 25 was calculated in fish for bis(2-ethylhexyl) terephthalate, using an estimated log Kow of 8.39 and a regression-derived equation. According to a classification scheme, this BCF suggests the potential for bioconcentration in aquatic organisms is low	[3]
Aerobic biodegradation	40.2 % (28 days) Biodegradable	[2]
	BOD20 = 0.15 g/g COD = 2.7 g/g ThOD = 2.58 g/g	[2]
	56% in 28 days	[7]
Anaerobic biodegradation	-
Metabolic pathway	-
Mobility	The Koc of bis(2-ethylhexyl) terephthalate is estimated as 2,000, using a water solubility of 4 mg/l and a regression-derived equation. According to a classification scheme, this estimated Koc value suggests that bis(2-ethylhexyl)terephthalate is expected to have slight mobility in soil.	[3]
Abiotic degradation	The rate constant for the vapor-phase reaction of bis(2-ethylhexyl) terephthalate with photochemically-produced hydroxyl radicals has been estimated as 2.2 x10-11 cm³/molecule-sec at 25ºC using a structure estimation method. This corresponds to an atmospheric half-life of about 18 hours at an atmospheric concentration of 5 x 10+5 hydroxyl radicals per cm³. A base-catalyzed second-order hydrolysis rate constant of 0.16 L/mole-sec was estimated using a structure estimation method; this corresponds to half-lives of 1.4 years and 51 days at pH values of 7 and 8, respectively. Bis(2-ethylhexyl) terephthalate does contain chromophores that absorb at wavelengths > 290 nm and therefore may be susceptible to direct photolysis by sunlight.	[3]
Volatilization	The Henry's Law constant for bis(2-ethylhexyl) terephthalate is estimated as 1.0 x10-5 atm m³/mole using a fragment constant estimation method. This Henry's Law constant indicates that bis(2-ethylhexyl) terephthalate is expected to volatilize from water surfaces. Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec) is estimated as 7.3 days. The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec) is estimated as 59 days. Bis(2-ethylhexyl) terephthalate's Henry's Law constant indicates that volatilization from moist soil surfaces may occur. Bis(2-ethylhexyl) terephthalate is not expected to volatilize from dry soil surfaces based upon an estimated vapor pressure of 2.1 x10-5 mm Hg, determined from a fragment constant method.
Conclusion
Physical-chemical	-
Emission	-
Exposure	-
Health	-
Environment	-
References
1	ESIS
2	SIDS Dossier. OECD HPV Chemical programme
3	HSDB
4	SRC physprod database
5	ChemID
6	CCRIS
7	EASTMANN

Sulfonic acids, C10 – C18-alkane, phenylesters, ASE

Glycerol Triacetate, GTA

Identification of the substance
CAS No.	102-76-1
EINECS No.	203-051-9	[1]
EINECS Name	triacetin	[1]
Synonyms	Glycerol triacetate GTA
Molecular Formula	C9H14O6	[1]
Structural Formula
Major Uses	Since triacetin has a variety of applications including as a plasticizer for cigarette filters and cellulose nitrate, solvent for the manufacture of celluloid, photographic films, fungicide in cosmetics, fixative in perfumery, component in binders for solid rocket fuels and a general purpose food additive, release of triacetin to the environment may occur at the production sites, specific industrial sites and consumers depending on the conditions of use in Japan	[2]
IUCLID	HPV	[1]
EU classification	This substance is not classified in the Annex I of Directive 67/548/EEC as such, but it may be included in one of the group entries.	[1]
Physico-chemical Characteristics
Physical Form	Liquid	[2]
	Colourless liquid with a fruity or fatty odour and a mild sweet tast that becomes bitter in cons. above 0.05%	[3]
Molecular Weight (g/mole)	218,21	[2]
pH	7	[2]
Melting Point/range (°C)	3ºC	[2]
Boiling Point/range (°C)	258ºC at 1,013 hPa	[2], [3]
Decomposition Temperature (°C)	-
Vapour Pressure (mm Hg at °C)	0.00248 mmHg at 25ºC [0.33 Pa] 0.003306hPa at 25ºC	[2]
	< 0.01 hPa at 20ºC [1 Pa, 0.0075 mmHg]	[4]
Density (g/cm3 at °C)	1.1562 at 25ºC	[2], [4]
Vapour Density (air=1)	7.52	[3]
Henry’s Law constant (atm/m³/mol at °C)	1.23 x 10-8	[2]
	1.2 x 10-8 at 25ºC	[3]
Solubility (mg/l water at °C)	70 g/l at 25ºC [70,000 mg/l]	[2], [4]
	58 g/l at 25ºC [58,000 mg/l]	[2], [4]
Partition Coefficient (log Pow)	0.21 at 25ºC	[2]
pKa	None	[2]
Flammability	Not flammable	[2], [4]
Auto flammability	432ºC	[2], [4]
Explosivity	Not explosive	[2], [4]
Oxidising Properties	Stable at normal temperatures and pressures under fire exposure conditions	[2]
Migration potential in polymer	-
Flash point	> 145ºC	[2], [4]
	138ºC	[3], [4]
Koc	10.5	[2]
logKow	0.36	[3]
Atmospheric OH rate constant cm³/(molecule sec)	7.810 x 10-12	[2]
	8.5 x 10-12 at 25ºC	[3]
Explosion limits	Lower: 1.05% Upper: 7.73%	[6]
Emission Data
During production	The production process consists of the batchwise controlled reaction of glycerol, acetic acid and acetic anhydride in a closed reaction system with adequate cooling facilities. This is followed by purification using vacuum distillation. The pungent nature of the raw materials demands a totally enclosed plant.	[4]
Exposure Data
Aquatic environment, incl. sediment	Environmental exposure: emission to aquatic compartment from waste water and evaporative emissions associated with its use in the perfume and cosmetic industries and its use as a solvent and CO2 remover from natural gas, and disposal of consumer products containing triacetin.	[2]
	SURFACE WATER: Triacetin was detected in a sample of Tennessee River water collected in Apr 1973 (concn not reported).	[3], [4]
	RAIN/SNOW: Triacetin was found in 1 out of 10 snow samples collected early March, 1998 from Finland, Russia and Siberia. The sample that contained 0.8 µg/kg of triacetin was from Moscow State University, Russia.	[3]
Terrestrial environment	-
Sewage treatment plant	Triacetin's production and use as a topical antifungal, fixative in perfumery, plasticizer, specialty solvent, as well as its use in the manufacture of cosmetics and removal of carbon dioxide from natural gas may result in its release to the environment through various waste streams.	[3]
	EFFLUENT CONCENTRATIONS: Triacetin was detected in secondary effluent samples from a rapid infiltration site in Fort Polk, LA sampled November 4-5, 1980 at concentrations of 0.024 and 0.51 µg/l.	[3]
Working environment	Occupational exposure: inhalation and dermal route in the industries.	[2]
	NIOSH has statistically estimated that 18,436 workers (4,103 are female) are potentially exposed to triacetin in the USA. Occupational exposure to triacetin may occur through inhalation and dermal contact with this compound at workplaces where triacetin is produced or used. The general population may be exposed to triacetin via inhalation and dermal contact from use of consumer products containing this compound.	[3]
Consumer goods	Consumer exposure: intake and dermal/inhalation route through the use as a food additive and topical antifungal and perfume fixative or cigarette filter, respectively.	[2]
	Due to its uses triacetin soon becomes diffused into small quanties and there is little possibility of large scale human contact or environmental effect after it leaves the manufacturers first line customers' premises. Its use is adhesive may give skin contact. As a carrier and solvent for food soft drinks flavouring materals ingestion will occur. Very small amounts can be found in cigarette smoke through a filter tip using triacetin as the plasticizer.	[4]
Man exposed from environment	-
”Secondary poisoning”	-
Atmosphere	-
Dermal	-
Toxicological data
Observations in humans	Very mild skin reaction One case report of contact eczema	[2]
	Ingestion: 7.8 mg/day/adult	[2]
	Commercial triacetin may contain diacetin, as well as monoacetin, and when applied to human eyes causes severe burning, pain and much redness of the conjunctiva, but no injury. Diacetin causes considerably more discomfort than pure triacetin.	[2], [4]
	Glycerol triacetate appears to be innocuous when swallowed, inhaled or in contact with the skin, but may cause slight irritation to sensitive individuals.	[2], [4]
	A case of allergic contact eczema in a 29 year-old patient in a cigarette factory is reported, which was based on sensitisation towards the triacetin used for the production of cigarette filters. The allergy was demonstrated in a patch test. In addition to triacetin, the di- and mono acetate of glycerol also produced positive tests. It seems reasonable to regard the reaction as an expression of a group sensitisation towards glycerol acetate.	[2]
	A Duhring-chamber test was conducted on 20 healthy volunteers The test substance was applied as 50% dilution for 24 hours. Result: Only very mild skin reactions were observed. The substance has good skin compatibility.	[2], [4]
	No skin reactions occurred in 33 volunteers treated with 20% triacetin in petrolatum in an attempt to induce skin sensitisation using the maximization test.	[2]
	Triacetin (20 % in petrolatum) did not irritate the skin of 33 volunteers when tested in a 48-hr covered patch test.	[2]
Acute toxicity
Oral	LD50 > 2,000 mg/kg (rat, combined)	[2], [4]
	LD50 = 3,000 mg/kg (rat)	[2], [4]
	LD50 = 6,400-12,800 mg/kg (rat)	[2], [4]
	LD50 = 12,700 mg/kg (rat)	[2]
	LD50 = 9,300 mg/kg (mouse, male)	[2], [4]
	LD50 = 1,800 mg/kg (mouse, male) LD50 = 1,100 mg/kg (mouse, female)	[2]
	LD50 = 3,200-6,400 mg/kg (mouse)	[2], [4]
	LD50 = 1,100 mg/kg (mouse)	[4]
	LD50 = 3,000 mg/kg (mouse)	[4]
	LD50 > 2,000 mg/kg (rabbit)	[4]
	LDL0 = 150 mg/kg (frog)	[4]
Dermal	LD50 > 2,000 mg/kg (rabbit)	[2], [4]
	LD50 > 5,000 mg/kg (rabbit)	[2], [4]
	LD50 > 20 ml/kg (guinea pig)	[2], [4]
Inhalation	LD50 > 1,721 mg/m³ (rat, combined, 4h) No lethal effects observed	[2], [4]
	NOAEL = 73,700 mg/m³ (5 days)	[2]
Other routes	-
Skin irritation	Not irritating (rabbit)	[2], [4]
Eye irritation	Not irritating (rabbit)	[2], [4]
Irritation of respiratory tract	-
Skin sensitisation	Not sensitising (guinea pig)	[2]
Subchronic and Chronic Toxicity
Oral	NOAEL = 1,000 mg/kg (rat, male) NOAEL = 1,000 mg/kg (rat, female)	[2]
	NOAEL = 10 g/kg per day (rat, 20% of diet)	[2]
Inhalation	NOAEL = 2,220 mg/m³ (rat, 90 day)	[2]
	NOAEL = 250 ppm (rat, 64 day)	[4]
	NOAEL = 8271 ppm (rat, 64 day)	[4]
Dermal	-
Metabolism	Triacetin has been administered iv to mongrel dogs. The majority of infused triacetin underwent intravascular hydrolysis, and the majority of the resulting acetate is oxidized. Triacetin was found to be hydrolyzed by human intestinal lipase.	[3]
	Triacetin is rapidly hydrolysed in vitro by all tissues of the organism including the gastrointestinal tract.	[3]
	Groups of female mongrel dogs to study the metabolic effects of isocaloric and hypercaloric infusions of 5% v/v aqueous triacetin. A primed, continuous infusion of 5 µmol/kg (0.3 µCi/kg/min) [13C]-acetoacetate and 1.0 µCi/kg (0.01 µCi/kg/min) [3H]-glucose was continued for 6 hr. Three hours after the start of the isotope infusion, dosing with triacetin was started. Six animals were infused at a rate of 47 µmol/kg/min and seven were infused at a rate of 70 µmol/kg/min triacetin for 3 hr. Blood and breath samples were taken at 15 to 30-min intervals. A group of four animals was infused with 70 µmol/kg/min glycerol and used as the control for the hypercaloric infusion. During isocaloric infusion of triacetin, plasma acetate and free fatty acid concentrations were significantly increased at 30 and 60 min, respectively, and remained elevated. During hypercaloric infusion, plasma acetate concentration increased progressively throughout the study, whereas the plasma free fatty acid concentration did not change. Plasma pyruvate and lactate concentrations were significantly decreased after 30 and 90 min, respectively, and throughout the study with both isocaloric and hypercaloric infusion. The plasma insulin concentrations were modestly increased during both infusions. Plasma glucose concentration was significantly decreased during isocaloric triacetin infusion; a slight but significant increase was observed with hypercaloric infusion. Glucose clearance decreased significantly in both groups during the last hour of triacetin infusion. Plasma ketone body concentrations increased significantly by 60 min, and they remained elevated with isocaloric infusion and increased progressively with hypercaloric infusion of triacetin; the increased concentrations were due to increased ketone body production. During the last hour of infusion, resting energy expenditure was significantly increased with isocaloric triacetin.	[3]
Absorption	Triacetin is more rapidly absorbed from the gastrointestinal tract in 3 hours than the other fats tested. Triacetin has been shown to be a source of liver glycogen and when fed in amounts equal in caloric value to 15% glucose it was utilized as efficiently as was glucose.	[3]
	Mongrel dogs were used to determine the systemic, hindlimb, gut, hepatic, and renal uptake of acetate during infusion of a 5% v/v aqueous solution of triacetin. A primed, continuous infusion of [1-14C]-acetate was continued for 7 hr with 10 animals. Three hours after the start of the tracer infusion, the animals were infused with triacetin at a rate of 47 µmol/kg/min for 4 hr. Blood and breath samples were taken at 15-min intervals for the last 30 min. Steady-state conditions were achieved in plasma acetate concentrations and specific activity and in expired [14-C02]. Plasma acetate concentrations were 1180, 935, 817, 752, and 473 µmol/L (all values approximate) in the aorta, renal vein, portal vein, femoral vein, and hepatic vein, respectively. The acetate turnover rate during triacetin infusion was 2214 µmol/min; systemic acetate turnover accounted for 68% of triacetin-derived acetate.	[3]
Mutagenicity, Genotoxicity and Carcinogenicity
Mutagenicity	S.typhimurium and E.coli (metabolic activator Sprague-Dawley rat liver (S9)) Cytotoxic conc: No toxicity with or without metabolic activation up to 5,000µg/plate (five strains) Genotoxic conc: No genotoxic effects observed with or without metabolic activation	[2]
	S.typhimurium and E.coli (metabolic activator Sprague-Dawley rat liver (S9)) Cytotoxic conc: No toxicity with or without metabolic activation up to 5,000µg/plate (four strains) Genotoxic conc: No genotoxic effects observed with or without metabolic activation	[2], [4]
Chromosome Abnormalities	Chinese Hamster Lung (metabolic activator Sprague-Dawley rat liver (S9)) Triacetin induced structural chromosome aberrations on shortterm treatment with an exogenous metabolic activation system at the maximum concentration of 2.2 mg/ml (10 mM). However, triacetin decreased pH of the medium at 2.2 mg/ml on short-term treatment with an exogenous metabolic activation system. Therefore, chromosome aberrations induced with triacetin were likely to be caused by lowering pH of the medium rather than by damaging DNA per se. It is, however, recognized that changes in pH of the medium caused by triacetin can induce such artifacts in this assay. Polyploidy was not induced under any of the conditions on continuous and short-term treatment with and without an exogenous metabolic activation system. With metabolic activation: Not observed up to 1.2 mg/ml for 6h exposure. The 50 % inhibition of cell proliferation was calculated to be 1.8 mg/ml. Without metabolic activation: Not observed up to 2.2 mg/ml for 24- and 48-h exposure. Genotoxic effects: Equivocal.	[2]
Other Genotoxic Effects	-
Carcinogenicity	-
Reproductive Toxicity, Embryotoxicity and Teratogenicity
Reproductive Toxicity	NOAEL = 1,000 mg/kg per day (rat m/f, reproduction) F1 NOAEL = 1,000 mg/kg per day (rat, offspring) Triacetin did not exert any toxic effects on reproductive parameters including the mating index, fertility index, gestation length, number of corpora lutea or implantations, implantation index, gestation index, delivery index and parturition or maternal behaviour at delivery and lactation. General parental toxicity: Triacetin had no effects on clinical signs, body weight, food consumption, and organ weight or necropsy findings. No histopathological changes ascribable to the compound were observed in either sex. There were no haematological or blood chemical parameters in males. The NOAEL for reproductive toxicity is thus considered to be 1,000 mg/kg bw/day for both sexes.	[2]
Teratogenicity	NOAEL = 1,000 mg/kg per day (maternal toxicity) NOAEL = 1,000 mg/kg per day (teratogenicity) No teratological or other developmental effects were observed at any dose. General parental toxicity: Triacetin had no effects on clinical signs, body weight, food consumption, and organ weight or necropsy findings. No histopathological changes ascribable to the compound were observed in either sex. There were no haematological or blood chemical parameters in males. Pregnancy/litter data: Triacetin did not exert any toxic effects on reproductive parameters including the mating index, fertility index, gestation length, number of corpora lutea or implantations, implantation index, gestation index, delivery index and parturition or maternal behaviour at delivery and lactation Toxicity to offspring: On examination of neonates, there were no significant differences in numbers of offspring or live offspring, the sex ratio, the live birth index, the viability index or body weight. No abnormal findings ascribable to the compound were found for external features, clinical signs or necropsy of the offspring. The NOAEL for reproductive and developmental toxicity is considered to be 1,000 mg/kg bw/day for parental animals and offspring.	[2]
Other Toxicity Studies	Sheep, 175 days (male and female) Each of two basal diets (pelleted, ground hay (H), and a pelleted mixture of the same hay and corn meal (HC) was supplemented singly with triacetin (Ac3) and glycerol (G). A given animal was fed continuously one of the four diets at one of two levels of intake (approximately, 1 or 2.2 times the maintenance level) during the 175-day feeding period. The mean rates with which the metabolizable energy (ME) ingested above the maintenance level of intake was utilized for body-energy gain, were: (in %) H + Ac3, 59.9; HC + G, 59.5; HC + Ac3, 63.7; and HC + G, 61.8(p > 0.3). Ignoring the kind of basal diet, utilization rates were 62.0 and 61.2 % for the ME provided by the diets containing triacetin and glycerol, respectively. The mean pooled net utilization of ME for body-energy gain by females (65.5%) was markedly greater (P<0.01) than that by males (57.6 %). In a series of respiration-calorimetric experiments, the net utilization of ME provided by the acetic acid moiety of triacetin was 76.4%, between days 50 and 70 of continuous feeding. Conclusion: In a 175 day feeding study with sheep, 62 % of metabolic energy was utilized. Concentration of triacetin in food was 10 %. No data on toxicity are reported.	[2], [4]
Toxicokinetics
Toxicokinetics	Dog Significant acetate uptake was demonstrated in all tissues (liver, 559 ± 68; intestine, 342 ± 23; hindlimb, 89 ± 7; and kidney, 330 ± 37 µmol/min). Conclusion: During intravenous administration in dogs, the majority of infused triacetin undergoes intravascular hydrolysis, and the majority of the resulting acetate is oxidized. Thus, energy in the form of short-chain fatty acids can be delivered to a resting gut via intravenous infusion of a short-chain triglyceride.	[2]
	Dog There were no changes in serum P or Ca. The serum Mg concentration decreased from 0.7 ± 0.03 to 0.57 ± 0.03 mmol/L (p < 0.001) by 90 min and remained at this level for the remainder of the study. The triacetin infusion did not influence fractional urinary Mg excretion; thus, the decrease in serum Mg was likely because of an increase in cellular transport of this cation. Conclusion: An isocaloric infusion of the short-chain triglyceride triacetin in dogs resulted in modest increases in plasma acetate but did not significantly affect serum Ca or P concentrations. Serum Mg decreased by approximately 20 %, probably because of cellular uptake rather than accelerated excretion. Triacetin administered to dogs at a rate approximating resting energy expenditure has no demonstrable adverse effects on mineral metabolism.	[2]
	Rat Triacetin caused no overt toxic effects at any point during the study. As the proportion of triacetin in the diet increased from 0 to 50 or 90 % of the lipid energy, cumulative nitrogen balance increased 50 or 120 %, respectively (p < 0.05). Whole-body and tissue leucine kinetics (determined during the last 2.5 hr of the 7-day study) were unaffected by the lipid composition of the diet. Plasma acetate concentration was not significantly different among groups. Conclusion: These results indicate that incorporation of triacetin in nutritionally balanced total parenteral nutrition formulas improves nitrogen balance with no overt toxic effects.	[2]
Ecotoxicity Data
Algae	EC50 > 1,000 mg/l (Selenastrum capricornutum, 72h) NOEC = 556 mg/l (Selenastrum capricornutum, 72h) Growth inhibition: growth rate and biomass	[2]
	Growth rate EC50 > 940 mg/l (Selenastrum capricornutum, 72h) NOEC = 460 mg/l (Selenastrum capricornutum, 72h) Biomass (AUG) EC50 > 1000 mg/l (Selenastrum capricornutum, 72h) NOEC = 560 mg/l (Selenastrum capricornutum, 72h)	[5]
Daphnia magna (acute)	EC50 = 888 mg/l (daphnia magna, 24h) EC50 = 768 mg/l (daphnia magna, 48h) EC0 = 309 mg/l (daphnia magna, 48h)	[2]
	EC50 > 974.4 mg/l (daphnia magna, 24h) EC50 = 810.9 mg/l (daphnia magna, 48h) EC0 = 541.1 mg/l (daphnia magna, 48h)	[2]
	EC50 = 380 mg/l (daphnia magna, 48h) EC0 = 65 mg/l (daphnia magna, 48h)	[2]
	EC0 = 65 mg/l (daphnia magna, 24h) EC50 = 380 mg/l (daphnia magna, 48h) EC100 = 1000 mg/l (daphnia magna, 48h)	[4]
	EC50 = 770 mg/l (daphnia magna, 48h) Acute immobilization	[5]
Daphnia magna (chronic)	EC50 > 100 mg/l (daphnia magna, 21d, reproduction) NOEC = 100 mg/l (daphnia magna, 21d, reproduction) LC50 > 100 mg/l (daphnia magna, 14d, parental) LC50 > 100 mg/l (daphnia magna, 21d, parental)	[2]
	EC50 > 94 mg/l (daphnia magna, 21d) NOEC > 94 mg/l (daphnia magna, 21d)	[5]
Other aquatic organisms	-
Fish (acute)	LC50 > 100 mg/l (Oryzia latipes, 96h)	[2], [5]
	LC50 = 165.3 mg/l (Pimephales promelas, 96h)	[2]
	LC50 = 174 mg/l (Cyprinus carpio, 48h)	[2]
	LC50 = 170 mg/l (Leuciscus idus, 48h)	[2]
	LC50 = 300 mg/l (Branchydanio rerio, 96h)	[2]
	LC0 = 100 mg/l (Cyprinus carpio, 48h) LC50 = 174 mg/l (Cyprinus carpio, 48h) LC100 = 320 mg/l (Cyprinus carpio, 48h)	[4]
	LC0 = 100 mg/l (Leuciscus idus, 48h) LC50 = 170 mg/l (Leuciscus idus, 48h) LC100 = 300 mg/l (Leuciscus idus, 48h)	[4]
Fish (chronic)	LC50 > 100 mg/l (Oryzia latipes, 14d) LC0 = 100 mg/l (Oryzia latipes, 14d)	[2], [5]
Bacteria	EC0 > 541.6 mg/l (Pseudomonas putida, 18h)	[2], [4]
	EC0 = 10,000 mg/l (Pseudomonas putida, 30 minutes)	[2], [4]
	NOEC = 3,000 mg/l (Pseudomonas putida, 16h) FOEC = 10,000 mg/l (Pseudomonas putida, 16h)	[2], [4]
Terrestrial organisms	-
Environmental Fate
BCF	1.3	[2], [4]
	An estimated BCF of 1 was calculated for triacetin, using a log Kow of 0.25 and a regression-derived equation. According to a classification scheme, this BCF suggests the potential for bioconcentration in aquatic organisms is low.	[3]
Aerobic biodegradation	77% after 14 days based on BOD 94% after 14 days based on TOC Readily biodegradable	[2]
	64% after 28 days based on ThCO2 (10 mg/l) 93% after 28 days based on ThCO2 (20 mg/l) Readily biodegradable	[2], [4]
	Triacetin, present at 100 mg/l, reached 91-94% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/l and the Japanese MITI test. Using a rapid infiltration system for treating primary and secondary effluents, triacetin, present in a feed solution at a concentration of 0.094 µg/l, was not detected in the column effluent. The specific loss process was not identified.	[3]
	79% after 30 days (5 mg/l) Readily biodegradable	[4]
	93% after 4 weeks based on BOD 97% after 4 weeks based on TOC Readily biodegradable	[5]
Anaerobic biodegradation	-
Abiotic degradation	The rate constant for the vapour-phase reaction of triacetin with photochemically-produced hydroxyl radicals has been estimated as 8.5 x10-12 cm³/(molecule-sec) at 25º C using a structure estimation method. This corresponds to an atmospheric half-life of about 1.9 days at an atmospheric concentration of 5 x 10+5 hydroxyl radicals per cm³. A base-catalyzed second-order hydrolysis rate constant of 6.2 x 10-1 l/(mole-sec) was estimated using a structure estimation method; this corresponds to half-lives of 130 and 12 days at pH values of 7 and 8, respectively. Triacetin does not contain chromophores that absorb at wavelengths à 290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight.	[3]
Photodegradation	T½ = 48h (indirect photolysis)	[2], [4]
Metabolic pathway	-
Mobility	-
Stability in water (abiotic)	Stable at pH 4 at 50ºC T½ = 60.4 days at pH 7 at 25ºC T½ = 16.5 h at pH 9 at 25ºC	[2]
	T½ = 130 days at pH 7 T½ = 1.3 h at pH 9 T½ = 13 days at pH 8	[4]
Soil adsorption/mobility	The Koc of triacetin is estimated as 33, using a log Kow of 0.25 and a regression-derived equation. According to a classification scheme, this estimated Koc value suggests that triacetin is expected to have very high mobility in soil.	[3]
	Based upon a measured water solubility of 58 g/l at 25ºC, the Koc-value can be estimated to be 10.5 from a regression derived equation. This Koc-value indicates very high soil mobility.	[4]
Volatilization from water/soil	The Henry's Law constant for triacetin is estimated as 1.2 x10-8 atm/m³/mol derived from its vapour pressure, 0.00248 mm Hg, and water solubility, 58,000 mg/l. This Henry's Law constant indicates that triacetin is expected to be essentially non-volatile from water surfaces. Triacetin's estimated Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to occur. Triacetin is not expected to volatilize from dry soil surfaces based upon a vapour pressure of 0.00248 mm Hg	[3]
	Based on a water solubility of 58 g/l and a vapour pressure of 0.00248 mmgHg at 25ºC, a Henry's law constant of 1.23 x 10-8 atm/m³/mol is estimated. This value indicates that the compound is essentially non-volatile from water.	[4]
Terrestrial fate	Based on a classification scheme, an estimated Koc value of 33, determined from a log Kow of 0.25 and a regression-derived equation, indicates that triacetin is expected to have very high mobility in soil. Volatilization of triacetin from moist soil surfaces is not expected to be an important fate process given an estimated Henry's Law constant of 1.2 x10-8 atm/m³/mol derived from its vapour pressure, 0.00248 mm Hg, and water solubility, 58,000 mg/l. Triacetin is not expected to volatilize from dry soil surfaces based upon a vapour pressure of 0.00248 mm Hg. A theoretical BOD of 91-94% in 4 weeks using an activated sludge inoculum and the Japanese MITI test suggests that biodegradation may be an important environmental fate process in soil	[3]
Aquatic fate	Based on a classification scheme, an estimated Koc value of 33, determined from a log Kow of 0.25 and a regression-derived equation, indicates that triacetin is not expected to adsorb to suspended solids and sediment. Volatilization from water surfaces is not expected based upon an estimated Henry's Law constant of 1.2 x 10-8 atm/m³/mol, derived from its vapour pressure, 0.00248 mm Hg, and water solubility, 58,000 mg/l. A base-catalyzed second-order hydrolysis rate constant of 6.2 x 10-1 l/mol/sec was estimated using a structure estimation method; this corresponds to half-lives of 130 and 12 days at pH values of 7 and 8, respectively. According to a classification scheme, an estimated BCF of 1, from its log Kow and a regression-derived equation, suggests the potential for bioconcentration in aquatic organisms is low. A theoretical BOD of 91-94% in 4 weeks using an activated sludge inoculum and the Japanese MITI test suggests that biodegradation may be an important environmental fate process in water.	[3]
Atmospheric fate	According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere, triacetin, which has a vapour pressure of 0.00248 mm Hg at 25ºC, is expected to exist solely as a vapour in the ambient atmosphere. Vapour-phase triacetin is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals, the half-life for this reaction in air is estimated to be 1.9, calculated from its rate constant of 8.5 x 10-12 cm³/(molecule-sec) at 25º C that was derived using a structure estimation method. Triacetin does not contain chromophores that absorb at wavelengths à 290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight.	[3]
Conclusion
Physical-chemical	-
Emission	-
Exposure	-
Health	-
Environment	-
References
1	ESIS
2	OECD SIDS final
3	HSDB
4	IUCLID dataset
5	MITI
6	MSDS Sigma Aldrich

Trimethyl pentanyl diisobutyrate, TXIB

Acetyl tributyl citrate, ATBC

Diisononyl adipate, DINA

12-(Acetoxy)-stearic acid, 2,3-bis(acetoxy)propyl ester)

Identification of the substance
CAS No.	36150-63-3 (COMGHA) 330198-91-9 (Component A, ca. 84%) 33599-07-4 (Component B, ca. 10%)	[1]
EINECS No.	451-530-8	[2]
EINECS Name	-
Synonyms	COMGHA Grinsted soft'n'safe Acetylated monoglycerides of fully hydrogenated castor oil. Acetic acid esters of monoglycerides of fully hydrogenated castor oil. 12-(Acetoxy)-stearic acid, 2,3-bis(acetoxy)-propylester
Molecular Formula	C27H48O8 (Component A) C25H46O6 (Component B)	[1]
Structural Formula
Major Uses	Plasticizer	[1]
IUCLID	-
EU classification
Physico-chemical Characteristics
Physical Form	Greasy substance with a slightly acid odour	[4]
Molecular Weight (g/mole)	500.7 (Component A) 442.6 (Component B)	[1]
Melting Point/range (°C)	- 21.5ºC	[1]
Boiling Point/range (°C)	300ºC at 1 atm (decomposition)	[1]
Decomposition Temperature (°C)	-
Vapour Pressure (mm Hg at °C)	< 2.8 x 10-4 Pa at 100ºC [2.1 x 10-6 mmHg]	[1]
	1.1 x 10-7 Pa at 25ºC [8.25 x 10-10 mmHg] 4.8 x 10-8 Pa at 20ºC [3.6 x 10-10 mmHg]	[3]
Density (g/cm3 at °C)	1.0030 at 20ºC	[3]
Vapour Density (air=1)	-
Henry’s Law constant (atm/m³/mol at °C)	-
Solubility (mg/l water at °C)	0.007 g/l [7 mg/l]	[1]
	< 0.33 mg/l at 20ºC pH ca. 6.8	[3]
Partition Coefficient (log Pow)	6.42	[4]
pKa	-
Flammability	-
Explosivity	-
Oxidising Properties	-
Migration potential in polymer	-
Log Kow	6.4	[1]
Koc	Immobile and remains preferably in soil	[3]
Flash point	244ºC at 101.3 kPa	[3]
Auto ignition tempetature	ca 370ºC	[3]
Emission Data
During production	-
Exposure Data
Aquatic environment, incl. sediment	-
Terrestrial environment	-
Sewage treatment plant	-
Working environment	-
Consumer goods	-
Man exposed from environment	-
”Secondary poisoning”	-
Atmosphere	-
Dermal	-
Toxicological data
Observations in humans	-
Acute toxicity
Oral	LC50 > 2000 mg/kg (rat)	[3]
Dermal	-
Inhalation	-
Other routes	-
Skin irritation	Not irritating (rabbit)	[3]
Eye irritation	Not irritating (rabbit)	[3]
Irritation of respiratory tract	-
Skin sensitisation	Not a skin sensitizer	[3]
Subchronic and Chronic Toxicity
Oral	Rat, 2-weeks No signs of toxicity (3%, 7.5% of the diet)	[3]
	Rat, 90 days (extream dose) NOAEL < 3 ml/kg per day	[3]
	Rat, 90 days (adequate dose) NOAEL = 5000 mg/kg per day	[3]
Inhalation	-
Dermal	-
Metabolism	Hydrolysis of the compound is incomplete and that a proportion of the administered dose passes through the gastrointestinal tract and is excreted unchanged.	[1]
	No significant absorption across gastrointestinal epithelium	[3]
Mutagenicity, Genotoxicity and Carcinogenicity
Mutagenicity	Not mutagenic in the Ames test	[3]
	Not clastrogenic in the in vitro mammalian cytogenetic test	[3]
Chromosome Abnormalities	Not mutagenic in the in vitro mammalian cell gene mutation test	[3]
Other Genotoxic Effects	-
Carcinogenicity	-
Reproductive Toxicity, Embryotoxicity and Teratogenicity
Reproductive Toxicity	-
Teratogenicity	-
Other Toxicity Studies	-
Toxicokinetics
Toxicokinetics	-
Ecotoxicity Data
Algae	EC50 = 106 mg/l (72h) 70-95% loss in concentration over test period	[3]
Invetebrates	EC50 = 0.92 mg/l (daphnia magna, 48h)	[3]
Other aquatic organisms	-
Fish	LC100 = 0.28 mg/l (zebra fish, 96h)	[3]
Bacteria	-
Terrestrial organisms	-
Activated sludge	EC20 > 143 mg/l EC50 > 143 mg/l No inhibitory effect of respiration rate	[3]
Environmental Fate
BCF	-
Aerobic biodegradation	98% after 28 days Ready biodegradable	[3]
Anaerobic biodegradation	-
Metabolic pathway	-
Mobility	-
Conclusion
Physical-chemical	-
Emission	-
Exposure	-
Health	-
Environment	-
References
1	SCENIHR
2	ESIS
3	Danisco
4	MSDS Danisco

| Front page | | Contents | | Back | | Printing instructions |

Version 1.0 November 2010, © Danish Environmental Protection Agency