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Sifosil

Existing Chemical Hazard Assessment NA/931HA

Jan 2018

NATIONAL INDUSTRIAL CHEMICALS NOTIFICATION AND ASSESSMENT SCHEME

GPO Box 58, Sydney NSW 2001 AUSTRALIA www.nicnas.gov.au

ISBN 978-0-9803124-3-0

© Commonwealth of Australia 2017This work is copyright. You may download, display, print and reproduce this material in unaltered form only (retaining this notice) for your personal, non-commercial use or use within your organisation. Apart from any use as permitted under the Copyright Act 1968, all other rights are reserved. Requests and inquiries concerning reproduction and rights should be addressed to Commonwealth Copyright Administration, Attorney General’s Department, National Circuit, Barton ACT 2600 or posted at http://www.ag.gov.au/cca .

PrefaceThis assessment was carried out under the National Industrial Chemicals Notification and Assessment Scheme (NICNAS). This scheme was established by the Industrial Chemicals (Notification and Assessment) Act 1989 (the Act), to aid in the protection of the Australian people and the environment by assessing the risks of industrial chemicals, providing information and making recommendations to promote their safe use. NICNAS assessments are carried out by staff employed by the Australian Government Department of Health in conjunction with the Australian Government Department of the Environment and Energy.

This assessment report is available for viewing and downloading from the NICNAS website or available on request, free of charge, by contacting NICNAS. For requests and enquiries please contact the NICNAS Administration Coordinator at:

Street address: Level 7, 260 Elizabeth Street, Surry Hills 2010, Australia

Postal address: GPO Box 58, Sydney NSW 2001, Australia

Telephone: + 61 2 8577 8800

Fax: + 61 2 8577 8888

Email: [email protected]

Website: www.nicnas.gov.au

DirectorNICNAS

National Industrial Chemicals Notification and Assessment Scheme, www.nicnas.gov.au ii

http://www.nicnas.gov.au/

ContentsPREFACE II

CONTENTS III

1. INTRODUCTION 1

1.1 Background 1

1.2 Substance identity 1

1.3 Use, volume and reformulation 1

2. HUMAN HEALTH HAZARD ASSESSMENT 2

2.1 Human health effects assessment 2

2.2 Hazard classification 9

3. ENVIRONMENTAL HAZARD ASSESSMENT 10

3.1 Environmental effects assessment 10

3.2 Predicted No-effect concentration 12

3.3 Hazard classification 13

REFERENCES 14

National Industrial Chemicals Notification and Assessment Scheme, www.nicnas.gov.au iii


1. Introduction 1.1 BackgroundThe notified chemical was assessed by NICNAS under a limited notification category in 2001 and is now listed on the Australian Inventory of Chemical Substances (AICS). In 2009, NICNAS was provided with an in vitro mammalian chromosomal aberration test and was notified by the original notifier of the intention to increase import volumes. At that time, the Director of NICNAS determined that secondary notification was not required and a report on the supplementary study was subsequently published.

In 2017, the notifier again informed NICNAS of their intention to increase import volumes, and of the availability of further hazard data. The hazard data consisted of a 90 day repeat dose oral toxicity study, a prenatal developmental toxicity study and an additional bacterial reverse mutation assay. NICNAS reviewed this new information and determined that secondary notification was not required as there was no significant change in the exposure scenario or risks from handling the chemical. In addition, the risk management controls recommended in the original assessment are sufficient to mitigate any potential risks from the additional hazards identified by this assessment. This report summarises all available hazard data on the notified chemical and presents a revised hazard classification. New data on the notified chemical are designated as ND.

This report does not reassess human or environmental exposures as there have been no changes to the end-use of the chemical, the reformulation process, the environmental release patterns or the environmental fate of the chemical. The exposure scenario, overall risk assessment and the recommended risk management controls, previously published by NICNAS is still considered relevant.

1.2 Substance identityCAS no: Confidential

Chemical name: Confidential

Marketing name/s: Sifosil (92% purity; ND; BASF, 2010)

Glysantin G 48-24

Engine Coolant G96

1.3 Use, volume and reformulationThe notified chemical is imported in products at concentrations of 0.49–2.69%, and reformulated into an anti-freeze coolant product (final concentration 0.15%) for automotive engines. The notified chemical is imported at up to 13 tonnes per year.

National Industrial Chemicals Notification and Assessment Scheme, www.nicnas.gov.au 1


2. Human health hazard assessment2.1 Human health effects assessmentThis is a summary of all data relevant to the human health hazard assessment of the notified chemical, with a focus on new data. The robust summaries of the new human health studies are summarised in this section and designated as ND.

Summary of toxicity data

Endpoint Result and Assessment Conclusion

Rat, acute oral 1000 < LD50 < 1470 mg/kg bw; harmful

Rat, acute dermal LD50 > 2000 mg/kg; low toxicity

Rabbit, skin irritation slightly irritating

Rabbit, eye irritation severely irritating

Guinea pig, skin sensitisation - Maximization test

no evidence of sensitisation

Rat, repeat dose oral toxicity - 28 days NOAEL = 9000 ppm

(equivalent to 806.4 mg/kg bw/day)*

Rat, repeat dose oral toxicity - 90 days (ND) NOAEL = 200 mg/kg bw/day

Genotoxicity - bacterial reverse mutation non mutagenic

Genotoxicity - bacterial reverse mutation (ND)

non mutagenic

Genotoxicity - in vitro mammalian chromosomal aberration test

non clastogenic

Genotoxicity - in vivo mammalian erythrocyte micronucleus test

non clastogenic

Developmental toxicity – prenatal study in the rat (ND)

NOAEL (maternal) = 200 mg/kg bw/day

NOAEL (developmental) = 400 mg/kg bw/day

LD50 = median lethal dose; NOAEL = no observed adverse effect level; *based on average male intake over days 7, 14, 21 and 28.

Acute toxicity

In an acute oral toxicity study (BASF AG, 1986a), Wistar rats were given 1000, 1470, 2150, or 3160 mg/kg body weight (bw) of the notified chemical by gavage. Doses of 3160 and 2150 mg/kg bw were lethal to all animals and a dose of 1470 mg/kg bw produced 60% mortality. Mortality was commonly associated with general congestive hyperaemia, haemorrhagic gastritis or atonic intestines. Clinical observations at doses of 1000 or 1470 mg/kg bw included dyspnoea, apathy, piloerection, staggering, spastic gait, dehydration and salivation. The LD50 by the oral route was thus between 1000 and 1470 mg/kg bw. On this basis, the notified chemical is considered to be harmful by the oral route.

In an acute dermal toxicity study (BASF AG, 1986b), the LD50 by the dermal route was determined to be greater than 2000 mg/kg bw in Wistar rats following semi-occlusive



application of the notified chemical with a single dose of 2000 mg/kg bw for 24 hours. No signs of systemic toxicity were observed, but animals showed oedema and full skin thickness necrosis at the application site.

Skin irritation

In a skin irritation study, aqueous solutions (40% concentration) of the notified chemical were applied to the clipped skin of three White Vienna rabbits for 4 hours under semi-occlusive conditions (BASF AG, 1986c). Scoring was performed (according to the Draize method) at 24 hours and again at 48 and 72 hours after removal of the test material. After exposure, very slight erythema was observed in one animal after 24 hours, which had resolved by 48 hours. No oedema was observed. This study indicated that a 40% solution of the notified chemical was slightly irritating to rabbit skin.

Although the notified chemical caused slight irritation in the above study, aqueous solutions of the notified chemical (at 35% concentrations) are very basic, with a pH of 13.2 (BASF AG, 2017; ND). Therefore, as confirmed from full skin thickness necrosis observed in a dermal toxicity study (BASF AG, 1986b), the neat chemical has the potential to cause skin (and eye) corrosion.

Eye irritation

In an eye irritation study (BASF AG, 1986d), undiluted notified chemical was instilled into the eyes of three White Vienna rabbits. Eyes were examined 1 and 24 hours following treatment. Very severe corneal opacity was observed after 1 hour, along with well-defined conjunctival chemosis in all animals. Iridial inflammation could not be determined due to severe opacity, as well as pus and blood discharge from the eyes of all animals at 24 hours. Due to the severity of the irritation, the study was discontinued after 24 hours. This study indicated that undiluted notified chemical was severely irritating to rabbit eyes.

Sensitisation

In a guinea pig maximisation study (BASF AG, 1987a), induction was performed with intradermal injections of 5% notified chemical in water and Freund's Complete Adjuvant (FCA), followed by dermal patches (15% notified chemical) applied under occlusion one week later. Challenge patches (10% notified chemical) were applied under occlusion on day 21, and 1 week later, for 24 hours. No erythema and/or oedema were observed after the first challenge, but 10% of the animals showed mild responses after the second challenge, which persisted for 48 hours. This study indicated that diluted notified chemical does not have skin sensitisation potential.

Repeated dose toxicity

In a 28-day oral study, Wistar rats received doses of 1000 ppm (average 94.3 mg/kg bw day in males), 3000 ppm (average 279.6 mg/kg bw day) or 9000 ppm (average 806.4 mg/kg bw day) in their drinking water. Body weight changes (reduced by 16 – 19%), and significantly increased plasma urea concentrations in male rats, were observed together with marked reductions in food and water consumption at the highest dose. A NOAEL of 9000 ppm (equivalent to 806.4 mg/kg bw day) was established.

A 90-day oral gavage study in rats (BASF AG, 2008; ND) was recently submitted to NICNAS, and established a much lower NOAEL. The robust study summary follows:



2.1.1 Repeat dose oral toxicity – 90 days (ND)

TEST SUBSTANCE Sifosil

METHOD OECD Test Guideline (TG) 408

Repeated Dose 90-Day Oral Toxicity Study in Rodents

EC Directive 2001/59/EC, B.26

Species/Strain Rat/Wistar

Route of administration Oral – gavage

Exposure information Total exposure: 90 days

Vehicle Water

RESULTS

Dose (mg/kg bw/day) Number and sex of animals Mortality0 10 male, 10 female 070 10 male, 10 female 0200 10 male, 10 female 0600 10 male, 10 female 3

In the high dose group (600 mg/kg bw/day), one male died on day 4, and two females on days 46 and 67. Deaths were considered associated with disseminated ulceration of the gastrointestinal tract from treatment.

Clinical observations

In the high dose group, occasional laboured respiration in 8 animals and noisy breathing in all animals from day 2 until the end of the study were noted. No substance-related adverse findings were observed in the lower dose groups.

Ophthalmic examination revealed no treatment-related findings.

Food consumption and bodyweight

No substance-related effects on food and water consumption were noted. In the high dose group, body weight was significantly decreased in males on several days of the study, and body weights were reduced in males throughout the study. No treatment-related effects were observed in females.

Laboratory findings - clinical chemistry, haematology, urinalysis

In the high dose group, decreased alkaline phosphatase activity, total protein, albumin, prothrombin time and globulin values were observed in both sexes. In addition, increased white blood cell counts were seen in both sexes. In high dose males, increased platelet counts, reticulocyte counts and cholesterol levels but decreased haemoglobin and haematocrit values were observed. In high dose females, increased potassium and triglyceride values, but decreased glucose levels were observed.

Pathology

In the high dose group, a slight increase in testes weight was observed. This was without histomorphologic correlates and dose-response and was considered not biologically relevant. Also in males, several relative organ weights were increased but these were considered secondary to decreased absolute body weights. No statistically significant changes in absolute or relative organ weights were observed in females.



In the high dose group, disseminated ulceration was observed in the forestomach and glandular stomach in approximately half of the animals in both sexes. Noting that spontaneous gastrointestinal ulceration is uncommon in rats, these were considered to be compound-related, local irritant effects from gavage treatment. No similar effects were observed in animals of the lower dose groups.

Remarks - Results

No treatment-related findings were observed in the low (70 mg/kg bw/day) or mid dose (200 mg/kg bw/day) groups. In the high dose group, 3 animals died. Mortality was considered linked to disseminated ulceration of the gastrointestinal tract from treatment with the test chemical. Based on the deaths observed at the high dose, the study established a NOAEL of 200 mg/kg bw/day.

CONCLUSION A NOAEL of 200 mg/kg bw/day was established in this study.

TEST FACILITY BASF AG (2008)

Genotoxicity

The notified chemical gave negative results in a bacterial reverse mutation test, using only Salmonella typhimurium (TA1535, TA1537, TA98 and TA100 strains), in the presence and absence of S9 metabolic activation (BASF AG, 1985a). An additional bacterial reverse mutation test (BASF AG, 2012; ND) recently submitted to NICNAS, on both Salmonella typhimurium and Escherichia coli, was also negative.

In addition, the notified chemical was non-clastogenic in an in vivo mammalian mouse erythrocyte micronucleus test (BASF AG, 1985b), and not clastogenic in Chinese hamster V79 cells in an in vitro mammalian chromosomal aberration test (RCC, 2007; ND).

The robust study summaries of the new bacterial reverse mutation test and in vivo mammalian erythrocyte micronucleus test are as follows:

2.1.2 Genotoxicity – bacteria (ND)


METHOD OECD TG 471 Bacterial Reverse Mutation Test

EC Directive 2008/440/EC, B.13/14

Species/Strain S. typhimurium: TA1535, TA1537, TA98 and TA100

E. coli: WP2 uvrA

Metabolic activation system

Liver S9 mix from induced rats

Concentration range in main test

With and without metabolic activation: 10, 33, 100, 333, 1000 and 2750 µg/plate

Vehicle Water

Remarks - Method No significant protocol deviations.

A preliminary toxicity test (33 – 5,500 µg/plate; plate incorporation) was performed for all strains to determine the toxicity of the test material. The results are reported as Test 1.

Positive control tests were conducted in parallel to the main



test using N-methyl-N'-nitro-N-nitrosoguanidine, 4-nitro-o-phenylene-diamine, 9-aminoacridine and 4-nitroquinoline-N-oxide in the absence of S9-mix, and 2-aminoanthracene with S9-mix.

RESULTS

Metabolic activation

Test substance concentration (µg/plate) resulting in:Cytotoxicity in main test Precipitation Genotoxic effect

AbsentTest 1 ≥ 2,750 > 5,500 NegativeTest 2 ≥ 1,000 > 5,500 NegativePresentTest 1 ≥ 2,750 > 5,500 NegativeTest 2 ≥ 1,000 > 5,500 NegativeRemarks - Results A weakly bacteriotoxic effect (reduction in the number of

revertants) was observed depending on strain and test conditions at ≥ 1,000 µg/plate.

No increases in the frequency of revertant colonies were recorded for any of the bacterial strains. No precipitate formation was observed.

The positive controls produced satisfactory responses, thus confirming the activity of the S9-mix and the sensitivity of the bacterial strains.

CONCLUSION The notified chemical was non mutagenic under the conditions of the test.


2.1.3 Genotoxicity - in vitro (ND)


METHOD OECD TG 473 In Vitro Mammalian Chromosomal Aberration Test

Species/Strain Chinese hamster

Cell Type/Cell Line V79 cells

Metabolic Activation System

S9 mix

Vehicle Water


Metabolic Activation

Test Substance Concentration (µg/mL)

Exposure Period (h)

Harvest time (h)

AbsentTest 1 600*, 900*, 1200* 4 18Test 2 150*, 300*, 600*

600*, 900*1818

1828

PresentTest 1 600*, 900*, 1200* 4 18



Test 2 900*, 1200*, 1500* 4 28*Cultures selected for metaphase analysis.

RESULTS

Metabolic Activation

Test Substance Concentration (µg/mL) Resulting in:Cytotoxicity in

Preliminary TestCytotoxicity in

Main TestPrecipitation Genotoxic

EffectAbsentTest 1 ≥1400 1200 >1200 1200Test 2 900 negativePresentTest 1 ≥1400 >1200 negativeTest 2 1500 >1500 negative

Remarks - Results In both experiments, either ethylmethane sulfonate or cyclophosphamide were used as positive controls and showed distinct increases in the number of cells with structural chromosomal aberrations.

A single statistically significant increase was observed in test 1 at preparation interval of 18 hours, 4 hours after treatment with 1200 µg/mL. In addition, the values at the scored concentrations increased in a dose-related manner. However, since all values were within the laboratory historical control data range, these observations are regarded as biologically irrelevant.

In both experiments, in the absence and presence of S9 mix, no biologically relevant increase in the number of cells carrying structural chromosomal aberrations was observed. The aberration rates of the cells treated with the notified chemical were close to the range of the solvent control values and within the range of laboratory historical control data.

CONCLUSION The notified chemical was not clastogenic to Chinese hamster V79 cells treated in vitro under the conditions of the test.

TEST FACILITY RCC (2007)

Based on the data available for this endpoint, there is no evidence the notified chemical is genotoxic.

Developmental toxicity

A prenatal development toxicity study (BASF AG, 2004; ND) was recently submitted to NICNAS, and the robust study summary follows:

2.1.4 Developmental toxicity (ND)


METHOD OECD TG 414 Prenatal Development Toxicity Study

EC Directive 2004/73/EC, B.31

Species/Strain Rat/Wistar (Crl:WI[Han])

Route of Administration Oral – gavage



Exposure Information Exposure days: day 6 through to day 19 of gestation

Vehicle Deionized water


RESULTS

Dose (mg/kg bw/day) Number and Sex of Animals

Mortality

0 (Control) 25 female 0200 (Low dose) 25 female 0400 (Mid dose) 25 female 0800 (High dose) 25 female 5

Mortality and Time to Death

Three high dose females died during treatment (days 10 – 12) and a fourth was near dead at sacrifice. One additional female died following a gavage error.

Effects on Dams

In the high dose group, statistically significant impairment of food consumption (on average 17% below concurrent controls) was observed, with the largest decrease during days 6 – 8 (50% below concurrent controls). Statistically significant impairment of body weight gain (on average 27% below concurrent controls) was also observed; however, this impairment was most significant during the corresponding period of reduced food consumption (days 6 – 8). The mid and low dose groups did not show a significant variation in food consumption, or body weight gain, compared to controls.

In the high dose group, apart from salivation, poor general state and piloerection were noted in two animals, one of which was not pregnant and was near death at sacrifice. The other also showed vaginal haemorrhage at day 20 and had 100% post implantation loss. In the mid dose group, salivation was noted after treatment on days 9 19 in some animals.

Dose-related stomach ulcerations were noted at necropsy in the mid and high dose groups (60% of high dose and 8% of mid dose). Clinical findings (e.g. poor general state and piloerection) in some high dose animals were considered by the study authors to be secondary to stomach ulceration.

Statistically significant mean post-implantation loss was observed in the high dose group (19.2% compared to 2.7% in controls), with 100% post-implantation loss in three dams . Only one of these dams appeared in poor health throughout the study. No other test-substance-related differences in conception rate were noted between dose groups and controls.

Effects on the Foetus

Incidental foetal external, soft tissue and skeletal malformations in all test groups, including controls, were observed. These effects were considered spontaneous in origin and not test substance-related. The study reported no evidence of an adverse effect of the notified chemical on foetal morphology.

Remarks – Results



Given the adverse developmental affects seen in the above study (increased post implantation loss) only occurred at levels that were maternally toxic, and in the absence of any other developmental or reproductive effects, this study indicates that the notified chemical is not a developmental toxicant.

The maternal NOAEL for systemic effects was 400 mg/kg bw/day based on increased incidence of mortality at 800 mg/kg bw/day. A dose-dependent increase in the incidence of stomach ulceration was observed at 400 mg/kg bw/day and above. Based on an increased post implantation loss in the high dose group, the developmental toxicity NOAEL was 400 mg/kg bw/day.

CONCLUSION

A maternal NOAEL of 400 mg/kg bw/day and a developmental toxicity NOAEL of 400 mg/kg bw/day were established in this study


2.2 Hazard classification The notified chemical was previously found to be a severe eye irritant, and harmful via the oral route. Hazard classification of R41 (Risk of Serious Damage to Eyes) and R22 (Harmful if swallowed), according to the Approved Criteria for Classifying Hazardous Substances (NOHSC, 1999), were recommended. Based on the available information, the notified chemical is recommended for hazard classification according to the GHS (United Nations, 2011), as adopted for industrial chemicals in Australia. The recommended hazard classification is presented in the following table.

Hazard classification Hazard statement

Eye irritant (Category 1) H318 – Causes serious eye damage

Skin Corrosion (Category 1B) H314 – Cause severe skin burns and eye damage

Acute toxicity (Category 4) H302 – Harmful if swallowed



3. Environmental hazard assessment 3.1 Environmental effects assessment This is a summary of all data relevant to the environmental hazard assessment of the notified chemical, with a focus on new data. The robust summaries of the new ecotoxicological studies are summarised in this section and designated as ND.

Summary of ecotoxicity data

Endpoint Result Assessment Conclusion

Fish toxicity 96 h LC50 = 342 mg/L not harmful to fish

Daphnia toxicity 24 h EC50 = 308 mg/L not harmful to aquatic invertebrates

Algal toxicity 72 h EbC50 > 100 mg/L

72 h ErC50 > 100 mg/L

not harmful to algae

Chronic Daphnia Toxicity (ND)

21 d NOEC ≥ 100 mg/L no long term hazard

EC50 = median effective concentration; LC50 = median lethal concentration; EbC50 = median effective concentration (algae biomass); ErC50 = median effective concentration (algae growth rate); NOEC = no observed effect concentration

Summary of microbial inhibition data

Endpoint Result Assessment Conclusion

Activated Sludge Respiration Inhibition (ND)

30 min IC50 > 1,000 mg/L not inhibitory to microbial activity

IC50 = median inhibitory concentration

An aquatic invertebrate chronic toxicity study (IBACON, 2008; ND) was recently submitted to NICNAS, and the robust study summary follows:

3.1.1 Chronic toxicity to aquatic invertebrates (ND)


METHOD OECD TG 211 Daphnia magna Reproduction Test – Semi static

EC Directive 2001/59/EC, C.20

Species Daphnia magna

Exposure Period 21 days

Auxiliary Solvent None

Water Hardness 250 mg/L as CaCO3

Analytical Monitoring There was no specific analytical method available for the test item. Therefore, dissolved organic carbon (DOC) content (determined by Shimadzu TOC-analyser TOC-V CPH) was used as a surrogate for the test item.

Remarks - Method In this study, the toxic effect of the notified chemical was



tested under semi-static conditions. One nominal test concentration was tested – 100 mg test item/L. Sub-lethal and survival endpoints were observed. The test conditions were stable with a water temperature of 19 – 20 °C; an oxygen concentration of >7.7 mg/L and pH of the test water of 6.8 – 8 (the pH did not vary >1.5 units). Test species were exposed to 16 h of light over each 24 h period.

The validity criteria of OECD TG 211 were all met: (a) there was 100% survival in both the control and test treatment group over the 21-day test period; and (b) the mean total number of offspring released per daphnid over the testing period for the control was 127.

There were no major deviations from the test guidelines.

The test media were observed to be clear and colourless with no undissolved test substance following preparation over the test exposure period (daily observations were made with new and old test media). Replicates of freshly prepared test media were taken at day 0, 7 and 16, and were analysed for DOC content. Control samples were also taken during the same periods for analysis. DOC analysis was determined to have acceptable recovery (70 to 110 % of nominal), but 3 samples were excluded due to sampling or measurement error.

RESULTS

Day 21

Nominal concentration

(mg/L)

Mean % of nominal

concentration (RSD)

Mean Percent Adult Survival (%)

Mean Number of Offspring Released

per Female-Cumulative (SD)

Mean Body Length of Surviving Parental

Daphnids (mm) (SD)

0 Not applicable 100 127 (12) 4.8 (0.20)100 111 (25) 100 130 (9.5) 4.8 (0.10)

LOEC (reproduction) ≥ 100 mg/L

NOEC (reproduction) ≥ 100 mg/L

Remarks - Results There was 100% survival in the control and the test treatment groups over 21 days of exposure to the notified chemical, and there were no signs of intoxication observed in the test animals over the test period. There was no reduction in offspring released per female or change in body length, in comparison with the control.

CONCLUSION The 21-day NOEC and LOEC for reproduction rate and survival of adults (based on nominal test concentration) was ≥100 mg test item/L, the only dose tested.

TEST FACILITY IBACON (2008)



Based on the ecotoxicological endpoints for the notified chemical, including the new information provided on aquatic invertebrate chronic toxicity, the notified chemical is not harmful to aquatic life and is not likely to pose a long-term hazard.

An activated sludge respiration inhibition test (BASF AG, 2005; ND) was recently submitted to NICNAS, and the robust study summary follows:

3.1.2 Inhibition of microbial activity (ND)


METHOD OECD TG 209 Activated Sludge, Respiration Inhibition Test – oxygen consumption

ISO Standard 8192

Inoculum Activated sludge from laboratory wastewater plant treating municipal sewage.

Exposure Period 30 minutes

Concentration Range 0 – 1,000 mg/L

Remarks – Method A range-finding test was conducted to determine the inhibitory effect of the notified chemical on the respiration rate of aerobic wastewater microorganisms of activated sludge. The test was carried out at 20 ± 2 °C.

The study met the validity criteria of the TG: (a) the oxygen consumption rate for the blank control was between 20 and 21 mg O2/L-h at the end of the test and, (b) the EC50 (3-h) of the reference item (3,5-dichorophenol) was 9 mg/L. The pH in the test treatment was 7.5 after 30 minutes of incubation and was relatively stable in the test treatment over the testing period.

RESULTS

EC50 1,000 mg/L

Remarks – Results The change in the O2 consumption rate when compared to the mean of the blank controls was approximately -10% over the 30-min incubation period.

CONCLUSION The EC50 (30-min) of the notified chemical is > 1,000 mg/L.


Based on the information provided from the microbial inhibition study, the notified chemical is not inhibitory to oxygen consumption by activated sludge, and hence is unlikely to affect biological methods of sewage treatment.

3.2 Predicted no-effect concentrationThe predicted no-effect concentration (PNEC) has been calculated from the acute ecotoxicological endpoint available for the most sensitive aquatic species, algae and an assessment factor. An assessment factor of 100 is used because at least three acute endpoints are available for aquatic species across three trophic levels.

PNEC for the Aquatic Compartment



ErC50 (Algae, 72 h) 100 mg/L

Assessment Factor 100

PNEC: 1 mg/L

3.3 Hazard classification The notified chemical was not classified according to the GHS (United Nations, 2011). This classification does not change based on the new ecotoxicological information provided. Environmental classification under the GHS is not mandated in Australia and carries no legal status but is presented for information purposes.



References BASF AG (1985a) Report on the study of Sifosil in the Ames Test. Project no. 40/1M0297/85. BASF AG, Department of Toxicology, Ludwigshafen/Rhein, Germany (unpublished report).

BASF AG (1985b) Cytogenetic investigations in NMRI mice after a single oral administration of Sifosil. Project no. 26M0297/8541. BASF AG, Department of Toxicology, Ludwigshafen/Rhein, Germany (unpublished report).

BASF AG (1986a) Report on the study of acute oral toxicity. BASF AG, Department of Toxicology, Ludwigshafen/Rhein, Germany (unpublished report).

BASF AG (1986b) Report on the acute irritation to the eye of the white rabbit. BASF AG, Department of Toxicology, Ludwigshafen/Rhein, Germany (unpublished report).

BASF AG (1986c) Report on the acute dermal irritation/corrosivity to the intact dorsal skin of the white rabbit. BASF AG, Department of Toxicology, Ludwigshafen/Rhein, Germany (unpublished report).

BASF AG (1986d) Report on the acute irritation to the eye of the white rabbit. BASF AG, Department of Toxicology, Ludwigshafen/Rhein, Germany (unpublished report).

BASF AG (1987a) Report on the maximisation test for the sensitising potential of Sifosil in guinea pigs. Project no. 30H297/85. BASF AG, Department of Toxicology, Ludwigshafen/Rhein, Germany (unpublished report).

BASF AG (1987b) Study of the oral toxicity of Sifosil P2R in rats. Administration in the drinking water over 4 weeks. Project no. 32S0297/8555. BASF AG, Department of Toxicology, Ludwigshafen/Rhein, Germany (unpublished report).

BASF AG (2004) Sifosil: Prenatal Developmental Toxicity Study in Wistar Rast Oral Administration (Gavage). Project no. 30R0214/05080. BASF AG, Department of Toxicology, Ludwigshafen/Rhein, Germany (unpublished report).

BASF AG (2005) Sifosil: Determination of the Inhibition of Oxygen Consumption by Activated Sludge in the Activated Sludge Respiration Inhibition Test. Project no. 08G0214/053055. BASF AG, Department of Toxicology, Ludwigshafen/Rhein, Germany (unpublished report).

BASF AG (2008) Sifosil: Repeated dose 90-day oral toxicity study in Wistar rats; Oral administration by gavage. Project no. 50R0214/05083. BASF AG, Department of Toxicology, Ludwigshafen/Rhein, Germany (unpublished report).

BASF SE (2010) Characterization of “Sifosil” before start of toxicology studies. Project no. 09L00428. BASF SE, Competence Center Analytics, Ludwigshafen, Germany (unpublished report).

BASF AG (2012) Sifosil: Salmonella Typhimurium/Escherichia Coli Reverse Mutation Assay. Project no. 40M0124/05M007. BASF AG, Department of Toxicology, Ludwigshafen/Rhein, Germany (unpublished report).

BASF AG (2017) Determination of pH of Engine Coolant G96. BASF AG, Department of Toxicology, Ludwigshafen/Rhein, Germany (unpublished report).



IBACON (2007) Influence of Sifosil to Daphnia magna in a Reproduction Test. Project no. 34531221. Institut fur Biologische Analytik und Consulting IBACON GlnbH, Rossdorf, Germany (unpublished report).

NICNAS (2001) Full Public Report: Sifosil (File No. NA/931). National Industrial Chemicals Notification and Assessment Scheme. Available at: website link

National Occupational Health and Safety Commission (NOHSC) (2004) Approved criteria for classifying hazardous substances [NOHSC:1008(2004)], National Occupational Health and Safety Commission, Australian Government Publishing Service, Canberra.

OECD (2002) Guidance Notes for Analysis and Evaluation of Repeat-Dose Toxicity Studies, OECD Publishing, Paris. Available at: http://dx.doi.org/10.1787/9789264078482-en

RCC (2007) In vitro chromosome aberration test in Chinese hamster V79 cells with Sofosil, RCC-CCR study number 1081500 (unpublished report).

United Nations (2011) Globally Harmonized System of Classification and Labeling of Chemicals (GHS) – Fourth Revised Edition (Study No. ST/SG/AC.10/30Rev.4, 2011). Geneva, Switzerland.



http://dx.doi.org/10.1787/9789264078482-en

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