4,4'-Isopropylidenediphenol, polymer with 1-chloro-2,3-epoxypropane, propane-1,2-diol acrylate and succinic anhydride

Endpoint summary

Description of key information

Based on the results of acute oral, dermal and inhalation toxicity studies, the test substance is considered to be of low acute toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 26 February, 2002 to 21 March, 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: CD rats of Sprague-Dawley origin (Hsd:Sprague-Dawley(CD))

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals chosen for this study were selected from a stock supply of healthy male and female CD rat of Sprague-Dawley origin (Hsd:Sprague-Dawley(CD)) obtained from Harlan U.K. Ltd., Bicester, Oxon, England. They were in the weight range of 100 to 141 g and approx 5-7 wk of age prior to dosing (Day 1). All the rats were acclimatised to the experimental environment for a minimum period of 5 d prior to the start of the study. Rats were allocated without conscious bias to cages within the treatment groups. They were housed in groups of 3 rats of the same sex in metal cages with wire mesh floors in Building F21 Room 28. A standard laboratory rodent diet (Special Diet Services RM1(E) SQC expanded pellet) and drinking water were provided ad libitum. Access to food only was prevented overnight prior to and approx 4 h after dosing. Each batch of diet used for the study was analyzed for certain nutrients, possible contaminants and micro-organisms. Results of routine physical and chemical examination of drinking water, as conducted by the supplier are made available to Huntingdon Life Sciences Ltd. at regular intervals throughout the year. Animal room environmental controls were set to maintain temperature within the range 22 ± 3°C and relative humidity 40-70%. Any minor deviations from these ranges would not have had an adverse effect on the animals and would not affect the integrity or validity of the study. These environmental parameters were recorded daily and the permanent record archived with other departmental raw data. Lighting was controlled by means of a time switch to provide 12 h of artificial light (0600 – 1800 GMT) in each 24 h period. Each animal was identified by tail marking.

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

The test substance was formulated at a concentration of either 20 or 200 mg/mL in DMSO and administered at a volume of 10 mL/kg bw. The test substance was prepared on the day of dosing. The absorption of the test substance was not determined. Chemical analysis of the homogeneity, stability and purity of the test substance was not undertaken as part of this study and remains the responsibility of the Sponsor.

Doses:

200 mg/kg bw, 2000 mg/kg bw

No. of animals per sex per dose:

3/sex/dose

Control animals:

no

Details on study design:

A group of six fasted rats (three males and three females) received a single oral gavage dose of the test substance, formulated in dimethylsulphoxide (DMSO), at a dose level of 200 mg/kg bw using a glass syringe and plastic catheter. As results at this dosage indicated the acute lethal oral dose of the test substance to be greater than 200 mg/kg bw, in compliance with the guidelines, a further group of six fasted rats (three males and three females) was similarly dosed at 2000 mg/kg bw to complete the study. The day of dosing was designated Day 1. Cages of rats were checked at least twice daily for any mortalities. Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity of the clinical signs and time were recorded at each observation. All animals were observed for 14 d after dosing. The bw of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bw were calculated. All animals were killed on Day 15 by carbon dioxide asphyxiation. All animals were subjected to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths following a single oral gavage dose of the test substance to a group of six rats (three males and three females) at a dose level of either 200 or 2000 mg/kg bw.

Clinical signs:

other: Clinical signs of reaction to treatment comprised of abnormal gait and piloerection, seen in all animals at both dosages. In addition, increased salivation (two males and all females at 200 mg/kg bw and all females at 2000 mg/kg bw), hunched posture (all

Gross pathology:

No abnormalities were revealed at the macroscopic examination at study termination on Day 15.

Interpretation of results:

other: not classified

Conclusions:

Under the conditions of the study, the acute oral lethal dose to rats of the substance was found to be greater than 2000 mg/kg bw.

Executive summary:

A study was performed to assess the acute oral toxicity of the test substance to the rat according to the OECD Guideline 423 and EU Method B.1 tris, in compliance with GLP. A group of six fasted rats (three males and three females) received a single oral gavage dose of the test substance, formulated in dimethylsulphoxide (DMSO), at a dose level of 200 mg/kg bw. As results at this dosage indicated the acute lethal oral dose of the test substance to be greater than 200 mg/kg bw, a further group of six fasted rats (three males and three females) was similarly dosed at 2,000 mg/kg bw. All animals were killed as scheduled and examined macroscopically on Day 15, the end of the observation period. Clinical signs of reaction to treatment comprised of abnormal gait and piloerection, seen in all animals at both dosages with increased salivation and hunched posture observed in rats at both dosages and pallor of the skin in animals at 2000 mg/kg only. Recovery of rats, as judged by external appearance and behaviour, was complete by Day 2. Animals were considered to have achieved satisfactory bodyweight gains throughout the study. No abnormalities were revealed at the macroscopic examination at study termination on Day 15. Under the conditions of the study, the acute oral LD50 of the test substance in rats was greater than 2,000 mg/kg bw (Blanchard, 2002).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The information requirements for this tonnage band is sufficiently met with the available data.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 29 October, 2002 to 16 November, 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

other: Limit test

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley Crl:CD® (SD) IGS BR strain rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female Sprague-Dawley Crl:CD® (SD) IGS BR strain rats were supplied by Charles River (UK) Ltd, Margate, Kent. On receipt the animals were randomly allocated to cages. After an acclimatization period of at least 5 d the animals were given a number unique within the study by ear punching and a number written on a colour coded cage card. At the start of the study the animals were approx 8 to 12 wk old. All male animals exceeded the weight range specified in the protocol (200 g – 350 g) with actual male bw in the range 357 g -380 g but this was considered not to affect the purpose or integrity of the study. The females were nulliparous and non-pregnant and within the required weight range. The animals were housed in groups of 5 by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes (Datesand Ltd., Cheshire, UK) and provided with environmental enrichment items: wooden chew blocks (B & K Universal Ltd, Hull, UK) and cardboard "fun tunnels" (Datesand Ltd., Cheshire, UK). With the exception of the exposure period, free access to mains drinking water and food (EU Rodent Diet 5LF2, IPS Limited, Wellingborough, Northants, UK) was allowed throughout the study. The diet, drinking water, bedding and chew blocks are routinely analysed and are considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. The environmental controls were set to achieve values of 21 ± 2°C and 55 ± 15% relative humidity. The rate of air exchange was at least 15 changes/h and the lighting was controlled to give 12 h continuous light and 12 h darkness. The animals were retained in this accommodation at all times except during the exposure period.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: acetone

Details on inhalation exposure:

The test substance formulation was aerosolised using a glass concentric jet nebuliser (Radleys, Saffron Walden, Essex, UK) located at the top of the exposure chamber. The nebuliser was connected to a glass syringe attached to an infusion pump, which provided a continuous supply of test substance formulation under pressure, and to a metered compressed air supply. Compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the nebuliser dust feed SAG 410. The cylindrical exposure chamber had a volume of approximately 30 L (dimensions: 28 cm diameter x 50 cm high). The concentration within the exposure chamber was controlled by adjusting the rate of the infusion pump. The extract from the exposure chamber passed through a 'scrubber' trap and was connected with a high efficiency filter to a metered exhaust system. The chamber was maintained under negative pressure. Homogeneity of the test atmosphere within the chamber was not specifically determined during this study. Chambers of the same design (ADG Developments Ltd, Hitchin, Herts, UK) have been fully validated and shown to produce evenly distributed atmospheres in the animals' breathing zone with a wide variety of test substances (Green J D et ai, 1984). Prior to the start of the study, test substance atmospheres were generated within the exposure chamber. During this characterisation period air flow settings, test substance formulation input rates and formulation details were varied to achieve the required atmospheric concentrations.

Analytical verification of test atmosphere concentrations:

no

Remarks:

However, chambers of the same design (ADG Developments Ltd, Hitchin, Herts, UK) have been fully validated and shown to produce evenly distributed atmospheres in the animals' breathing zone with a wide variety of test substances (Green J D et al, 1984).

Duration of exposure:

4 h

Concentrations:

The rats were exposed to an aerosol atmosphere of a formulation of the test substance (60% test subsatnce : 40% acetone w:w).

No. of animals per sex per dose:

5/sex

Control animals:

no

Details on study design:

Sighting Exposure: During characterisation, a group of two rats (one male, one female) was exposed to an atmosphere of the test substance formulation at an approx concentration of 2 mg/L for approx 4 h. No significant effects were noted for the animals.

Exposure procedure: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber 'O' ring. Only the nose of each animal was exposed to the test atmosphere. Following an appropriate equilibration period a single group of ten rats (five males and five females) was exposed to an atmosphere of the test material, generated from the formulation, for a period of 4 h. Based on the results of the sighting exposure, a target concentration of 5 mg/L was used for the exposure. As no deaths occurred and the mean achieved concentration was 98% of target, no further levels were required.

Exposure chamber temperature and relative humidity: The temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/humidity meter (Hanna Instruments Ltd, Beds., UK) located in a vacant port in the animals' breathing zone of the chamber and recorded every 30 min throughout the 4 h exposure period.

Exposure Chamber Oxygen Concentration: Oxygen levels within the exposure chamber were measured by an electronic oxygen analyser (Servomex (UK) Ltd, Crowborough, East Sussex) located in a sampling port in the animals breathing zone during each exposure period. The test atmosphere was generated to contain at least 19% oxygen.

Exposure Chamber Atmosphere Concentration: The actual chamber concentration was measured at regular intervals during the exposure period. The gravimetric method used employed glass fibre filters (Gelman type A/E 25 mm) placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals breathing zone and a suitable, known volume of exposure chamber air was drawn through the filter using a vacuum pump. Each filter was weighed before and after sampling in order to calculate the weight of collected test substance. The difference in the two weights, divided by the volume of atmosphere sampled, gave the actual chamber concentration (assuming total volatilisation of the acetone component). The nominal chamber concentration was calculated by dividing the mass of test substance used by the total volume of air passed through the chamber.

Particle size distribution: The particle size of the generated atmosphere inside the exposure chamber was determined three times during the exposure period using a Marple Personal Cascade Impactor (Schaefer Instruments Ltd, Oxon., UK). This device consisted of six impactor stages (9.8, 6.0, 3.5, 1.55, 0.93 and 0.52 µm cut points) with stainless steel collection substrates and a back up glass fibre filter, housed in an aluminium sampler. The sampler was temporarily sealed in a sampling port in the animals' breathing zone and a suitable, known volume of exposure chamber air was drawn through it using a vacuum pump. The collection substrates and backup filter were weighed before and after sampling and the weight of test substance, collected at each stage, calculated by difference. The mean amount for each stage was used to determine the cumulative amount below each cut–off poin size. In this way, the proportion (%) of aerosol less than 9.8, 6.0, 3.5, 1.55, 0.93 and 0.52 µm was calculated. The resulting values were converted to probits and plotted against log10 cut-point size. From this plot, the Mass Median Aerodynamic Diameter (MMAD) was determined (as the 50% point) and the geometric standard deviation was calculated. In addition the proportion (%) of aerosol less than 4 µm (considered to be the respirable portion) was determined. All particle size distribution calculations were performed using a purpose designed computer programme (Chrom Series Data Server and Reg 2000 Graph Plotter).

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4 900 other: mg/m3 (mean achieved atmosphere concentration)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No

Clinical signs:

other: Common abnormalities noted during the study included increased respiratory rate, noisy respiration, hunched posture, pilo-erection and wet fur and there were instances of laboured respiration, ptosis and red/brown staining around the eyes or snout. All an

Body weight:

Normal bodyweight development was noted during the study. Several females showed reduced bodyweight gain during Week 1 or 2 of the study but such variations are not uncommon in female rats of this strain or age and are considered not to be significant.

Gross pathology:

No macroscopic abnormalities were detected at necropsy.

The mean atmosphere concentration of test substance was as follows:

Atmospheric concentration
Mean achieved (mg/L)	Standard deviation	Nominal (mg/L)
4.9	0.47	21.1

 

The characteristics of the achieved atmosphere were as follows:

Mean achieved atmosphere concentration (mg/L)	Mean mass median aerodynamic diameter (µm)	Inhalable fraction (% <4µm)	Geometric standard deviation
4.9	1.17	97.9	1.83

Interpretation of results:

other: Category 4

Conclusions:

Under the conditions of the study, the 4h LC50 of the substance in rat was considered to be greater 4900 mg/m3.

Executive summary:

A study was performed to assess the acute inhalation toxicity of the test substance according to the OECD Guidelines 403 and EU Method B2, in compliance with GLP. A group of 10 Sprague-Dawley Crl:CD® (SD) IGS BR strain rats (fine males and five females) was exposed to an aerosol atmosphere of a formulation of the test substance (60% test substance: 40% acetone w:w) for 4 h using a nose only exposure system, followed by a 14 d observation period. No deaths occurred in a group of 10 rats exposed to a mean achieved atmosphere concentration of 4,900 mg/m3. Under the conditions of the study, the 4h LC50 of the substance in rat was considered to be greater 4,900 mg/m3 (Wesson, 2003).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

4 900 mg/m³ air

Quality of whole database:

The information requirements for this tonnage band is sufficiently met with the available data.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 22 March, 2002 to 5 April 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

other: Limit test

Limit test:

yes

Species:

rat

Strain:

other: CD rats of Sprague-Dawley origin (Hsd:Sprague-Dawley (CD))

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals chosen for this study were selected from a stock supply of healthy male and female CD rats of Sprague-Dawley origin (Hsd:Sprague-Dawley (CD)) obtained from Harlan U.K. Ltd., Bicester, Oxon, England. They were in the weight range of 227 to 285 g and approx 8-11 wk of age prior to dosing (Day 1). All the rats were acclimatised to the experimental environment for a period of 8 d prior to the start of the study. The rats were allocated without conscious bias to cages within the treatment group. They were housed individually in metal cages (RS Biotech Sub-Dividable Rodent Cages - polished stainless steel) until Day 5 when they were returned to group housing. The cages were fitted with grid floors to ensure rapid removal of waste material to undertrays. The cages were suspended in mobile stainless steel racks in Building F21 Room 28. A standard laboratory rodent diet (Special Diet Services RMl(E) SQC expanded pellet) and drinking water were provided ad libitum. The batch (es) of diet used for the study was analyzed by the Supplier for certain nutrients, possible contaminants and micro-organisrns. Results of routine physical and chemical examination of drinking water, as conducted by the supplier, are made available to Huntingdon Life Sciences Ltd. at regular intervals throughout the year. Animal room environmental controls were set to maintain temperature within the range 22 ± 3°C and relative humidity 40 - 70%. Any minor deviations from these ranges would not have had an adverse effect on the animals and would not affect the integrity or validity of the study. These environmental parameters were recorded daily and the permanent record archived with other departmental raw data. Lighting was controlled by means of a time switch to provide 12 h of artificial light (0600 - 1800 hours GMT) in each 24 h period. Each animal was identified by tail marking. Each cage was identified by a coloured label displaying the dose level, study schedule number, animal mark and the initials of the Study Director and Home Office licensee.

Type of coverage:

semiocclusive

Vehicle:

propylene glycol

Details on dermal exposure:

One day prior to treatment, hair was removed from the dorso-lumbar region of each rat with electric clippers taking care to avoid damaging the skin, exposing an area equivalent to approx 10% of the total body surface area. The test substance was applied by spreading it evenly over the prepared skin. The treatment area (approx 50 mm x 50 mm) was covered with porous gauze held in place with a non-irritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the animal. Treatment in this manner was performed on Day 1 (day of dosing) of the study only.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex

Control animals:

not required

Details on study design:

Dose level (volume): 2000 mg/kg bw (5 mL/kg bw)
DOSAGE PREPARATION: The test substance was formulated at a maximum practical concentration of 40% wlv in propylene glycol.
Duration of observation period following administration: 14 d
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy of survivors performed: Yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No systemic response to treatment following a single dermal application. Very slight dermal irritation (Grade 1 erythema with or without Grade 1 oedema or Grade 1 oedema only) was observed in one male and two females following removal of the dressings, re

Gross pathology:

No abnormalities were revealed at the macroscopic examination at study termination on Day 15.

Interpretation of results:

other: not classified

Conclusions:

Under the test conditions, the dermal LD50 of the substance in rats was > 2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance according to OECD Guideline 402 and EC Method B.3, in compliance with GLP. A group of 10 rats (five males and five females) received a single topical application of the test substance, formulated at a maximum practical concentration in propylene glycol, corresponding to a dose level of 2,000 mg/kg bw. All animals were killed and examined macroscopically on Day 15, the end of the observation period. There was no systemic response to treatment in any animal throughout the study. Very slight dermal irritation (Grade 1 erythema with or without Grade 1 oedema or Grade 1 oedema only) was observed in three animals following removal of the dressings, resolving completely by Day 4. No dermal irritation was noted in the remaining seven animals throughout the study. A low bodyweight gain was recorded for one male and three females on Day 8 and one female on Day 15. All other animals were considered to have achieved satisfactory bodyweight gains throughout the study. No abnormalities were revealed at the macroscopic examination at study termination on Day 15. Under the test conditions, the acute dermal LD50 of the test substance in rats was greater than 2,000 mg/kg bw (Blanchard, 2003).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The information requirements for this tonnage band is sufficiently met with the available data.

Additional information

Oral:

A study was performed to assess the acute oral toxicity of the test substance ‘4,4'-Isopropylidenediphenol, polymer with 1-chloro-2,3-epoxypropane, propane-1,2-diol acrylate and succinic anhydride’ to the rat according to the OECD Guideline 423 and EU Method B.1 tris, in compliance with GLP. A group of six fasted rats (three males and three females) received a single oral gavage dose of the test substance, formulated in dimethylsulphoxide (DMSO), at a dose level of 200 mg/kg bw. As results at this dosage indicated the acute lethal oral dose of the test substance to be greater than 200 mg/kg bw, a further group of six fasted rats (three males and three females) was similarly dosed at 2,000 mg/kg bw. All animals were killed as scheduled and examined macroscopically on Day 15, the end of the observation period. Clinical signs of reaction to treatment comprised of abnormal gait and piloerection, seen in all animals at both dosages with increased salivation and hunched posture observed in rats at both dosages and pallor of the skin in animals at 2000 mg/kg only. Recovery of rats, as judged by external appearance and behaviour, was complete by Day 2. Animals were considered to have achieved satisfactory bodyweight gains throughout the study. No abnormalities were revealed at the macroscopic examination at study termination on Day 15. Under the conditions of the study, the acute oral LD50 of the test substance in rats was greater than 2,000 mg/kg bw (Blanchard, 2002).

 

Inhalation:

A study was performed to assess the acute inhalation toxicity of the test substance ‘4,4'-Isopropylidenediphenol, polymer with 1-chloro-2,3-epoxypropane, propane-1,2-diol acrylate and succinic anhydride’ according to the OECD Guidelines 403 and EU Method B2, in compliance with GLP. A group of 10 Sprague-Dawley Crl:CD® (SD) IGS BR strain rats (fine males and five females) was exposed to an aerosol atmosphere of a formulation of the test substance (60% test substance: 40% acetone w:w) for 4 h using a nose only exposure system, followed by a 14 d observation period. No deaths occurred in a group of 10 rats exposed to a mean achieved atmosphere concentration of 4,900 mg/m3. Under the conditions of the study, the 4h LC50 of the substance in rat was considered to be greater 4,900 mg/m3 (Wesson, 2003).

 

Dermal:

A study was conducted to determine the acute dermal toxicity of the test substance ‘4,4'-Isopropylidenediphenol, polymer with 1-chloro-2,3-epoxypropane, propane-1,2-diol acrylate and succinic anhydride’ according to OECD Guideline 402 and EC Method B.3, in compliance with GLP. A group of 10 rats (five males and five females) received a single topical application of the test substance, formulated at a maximum practical concentration in propylene glycol, corresponding to a dose level of 2,000 mg/kg bw. All animals were killed and examined macroscopically on Day 15, the end of the observation period. There was no systemic response to treatment in any animal throughout the study. Very slight dermal irritation (Grade 1 erythema with or without Grade 1 oedema or Grade 1 oedema only) was observed in three animals following removal of the dressings, resolving completely by Day 4. No dermal irritation was noted in the remaining seven animals throughout the study. A low bodyweight gain was recorded for one male and three females on Day 8 and one female on Day 15. All other animals were considered to have achieved satisfactory bodyweight gains throughout the study. No abnormalities were revealed at the macroscopic examination at study termination on Day 15. Under the test conditions, the acute dermal LD50 of the test substance in rats was greater than 2,000 mg/kg bw (Blanchard, 2003).

Based on the results of acute oral, dermal and inhalation toxicity studies, the test substance is considered to be of low acute toxicity.

Justification for classification or non-classification

Based on the results of acute oral, dermal and inhalation toxicity studies, the test substance is not required to be classified for acute toxicity according to EU CLP (EC 1272/2008) criteria.