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REACH

3-[(phenylcarbamoyl)amino]phenyl 4-methylbenzenesulfonate

EC number: 866-700-0 | CAS number: 2102522-55-2

Life Cycle description
Uses advised against

Toxicological information

Endpoint summary

Administrative data

Description of key information

Acute oral toxicity (Appl 2017)

Under the conditions of the study, the acute oral LD50 of the test material was determined to be > 2000 mg/kg bw in female rats.

Acute inhalation toxicity (Nagy 2021)

Under the conditions of this study the 4-hour LC50 of the test material in rats was considered to be > 3.38 mg/L since no adverse effectd were noted at the highest attainable test concentration.

Acute dermal toxicity (Tsubokura 2018)

Under the conditions of the study the acute dermal toxicity of the test material to rats was considered to be > 2000 mg/kg bw.

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:

28 March 2017 - 12 April 2017

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)

Version / remarks:

17 December 2001

Deviations:

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Deviations:

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

1998

Deviations:

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Cr1: WI Wistar rats

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: Yes.
- Age at study initiation: 9 weeks old
- Weight at study initiation: 210 - 231 g
- Fasting period before study: On the night before treatment, the animals were fasted. The food but not water was withheld during an overnight period. Animals were weighed before treatment. The test material was administered by oral gavage in the morning. The food was returned 3 hours after the treatment.
- Housing: 3 animals/cage in Type II. polypropylene/polycarbonate cages. Animals were housed by group to allow social interaction and with deep wood sawdust bedding to allow digging and other normal rodent activities.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 13 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 20.1 – 25.0 °C
- Humidity: 35 – 67 %
- Air changes: 15 - 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

1% solution

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Preparation: Prepared from Methyl cellulose powder and distilled water
- Lot/batch no.: 511582

DOSE PREPARATION
- The test material was freshly formulated at a concentration of 200 mg/mL in the vehicle, in the test facility on the day of administration.
- The formulation container was magnetic stirred continuously up to the end of dose administration procedures.

CLASS METHOD
- Rationale for the selection of the starting dose: The initial dose level was selected to be that which is most likely to produce mortality in some of the dosed animals.
- In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.
- Initially, three female animals were treated with 2000 mg/kg bw of the test material. No mortality was observed, therefore further 3 animals were treated at the dose level of 2000 mg/kg bw. As no mortality was observed in this second dose group, further testing was not required according to the test guidelines.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

In total 6 female animals were treated.

Control animals:

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0), weekly thereafter and at necropsy (Day 14).
- Necropsy of survivors performed: Yes. Macroscopic examination was performed on all animals. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed.
- Examinations performed: Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Statistics:

The method used was not intended to allow the calculation of a precise LD50 value. The test material was ranked into categories of Globally Harmonized Classification System (GHS (rev. 6) 2015). Clinical signs, body weight, body weight gain and gross macroscopic data were tabulated.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test material did not cause mortality at a dose level of 2000 mg/kg bw in any animal.

Clinical signs:

other: All animals were symptom-free during the observation period at a dose level of 2000 mg/kg bw.

Gross pathology:

There was no evidence of the macroscopic changes at a dose level of 2000 mg/kg bw in any animal.

Clinical observations, dose level 2000 mg/kg bw, Treatment on Day 0, Sex: Female

Cage No.

Animal No.

Observations

Observation Days

7-14

Frequency

30 min

7323

Symptom Free

20/20

7324

Symptom Free

20/20

7325

Symptom Free

20/20

7326

Symptom Free

20/20

7327

Symptom Free

20/20

7328

Symptom Free

20/20

+ = present

h = hour(s)

‘ = minute

Frequency of observation = number of occurrence of observation / total number of observations

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

Under the conditions of this study, the acute oral LD50 of the test material was determined to be > 2000 mg/kg bw in female rats.

Executive summary:

During the study, two groups of three female Crl:WI rats were treated with the test material at a dose level of 2000 mg/kg body weight (bw) (Group 1 and Group 2). A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test material was administered at the dose level of 2000 mg/kg bw. Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group; therefore, no further testing was required.

Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0, 7 and before necropsy (Day 14). All animals were subjected to a necropsy and a macroscopic examination.

Under the conditions of the study, the test material did not cause mortality at a dose level of 2000 mg/kg bw. All animals were symptom-free during the observation period at a dose level of 2000 mg/kg bw. There were no treatment related body weight changes. A slight decrease was detected in body weight between Day 7 and Day 14 in one animal however this fact was considered to have no toxicological significance. Body weights were within the range commonly recorded for this strain and age. There was no evidence of the macroscopic changes at a dose level of 2000 mg/kg bw.

The acute oral LD50 of the test material was therefore determined to be > 2000 mg/kg bw in female rats.

Endpoint conclusion

Endpoint conclusion:: no adverse effect observed
Dose descriptor:: LD50
Value:: > 2 000 mg/kg bw
Quality of whole database:: The study was conducted according to standardised guidelines, in compliance with GLP, and as such was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

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:

8 October 2020 - 22 October 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

7 September 2009

Deviations:

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Deviations:

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

August 1998

Deviations:

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

yes

Specific details on test material used for the study:

- The original test material (as supplied) could not be used to produce an appropriate atmosphere because during technical tests it had been proven that it is not suitable for atmosphere generation due to the physical properties of the test material (specifically - its sticky nature). Therefore, the test material was micronized by a ball mill (Pulverisette 6, Fritsch GmbH Germany) in order to increase the number of particles under 4 μm.
- The test material was milled in two phases. In the first phase, the test material (approximately 30 g) was loaded in stainless steel grinding bowl of size 250 mL with stainless steel grinding balls (Ø 10 mm / 100 pieces) and with appropriate milling settings it was milled, rotational speed of 600 rpm for 3 mins with 5 mins break, this cycle was performed four times.
- In the second phase, the previously ground test material (approximately 30 g) was loaded in the agate grinding bowl of size 250 mL with agate grinding balls (Ø 5 mm / 390 pieces) and with appropriate milling settings it was milled, rotational speed of 400 rpm for 1 min with 5 mins break, this cycle was performed two times.
- For the technical trials and animal exposure the test material which was milled according to the milling settings mentioned above was used.
- Prior to the animal exposure a range of technical trials with original milled test material were performed in order to prove that the most optimal MMAD was selected for the main study (ie that which would attain the highest possible test concentration).
- Different milling tests and technical trials with the original and/or milled test material were performed in order to achieve the target concentration of 5 mg/L, but none of them was proved to be effective, as due to the sticky nature of the milled test material the target concentration of 5 mg/L could not be reached, therefore the main study was performed by the exposure of animals to the maximum attainable concentration (~3 mg/L) with optimum particle size distribution around 4 μm MMAD.

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult rats, 8-9 weeks old
- Weight at study initiation: 315 - 341 g (males), 175 - 185 (females). The weight variation did not exceed ± 20 % of the mean weight for either sex.
- Housing: Group caging (up to 3 animals, by sex, per cage), in Polypropylene/polycarbonate (type III) cages with stainless steel mesh lids. Rats were group-housed to allow social interaction, and with deep wood sawdust bedding, to allow digging and other normal rodent activities.
- Diet: ad libitum.
- Water: ad libitum.
- Acclimation period: 6 days. (Animals were also acclimatised to the test apparatus (restrain procedures) for a short period (1 hour) prior to testing in order to lessen the stress during exposure.)
- Method of randomisation in assigning animals to test and control groups: The animals were set in order of their bodyweight. The animals were randomly assigned to test groups using a randomization scheme. The randomization was checked according to the actual bodyweights verifying the homogeneity and deviations between the groups.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: Above 10 air exchanges/hour by central air-conditioning system.
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

3.72 µm

Geometric standard deviation (GSD):

2.18

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Prior to animal exposure, test material atmospheres were generated within the exposure chamber. During this period, airflow settings, test material input and the atmosphere generation system was varied to achieve the required atmospheric concentrations and constancy.

- Exposure apparatus: Anodised aluminium Flow Past Exposure Chamber (TSE Systems GmbH, Bad Homburg, Germany). The test material was aerosolised using a Rotating Brush Generator, RBG 1000 (Palas GmbH, Greschbachstraße 3 b, 76229 Karlsruhe, Germany) located at the top of the exposure chamber. Compressed air was supplied by means of an oil-free compressor and passed through a suitable filter system prior to introduction to the dust generator.
- Method of holding animals in test chamber: The animals were held in polycarbonate restraint tubes located around the chamber which allowed only the animal’s nares to enter the exposure port.
- Source and rate of air (airflow): Fresh aerosol from the generation system was constantly supplied to the inner plenum (distribution chamber) of the exposure system from where, under positive pressure, it was distributed to the individual exposure ports. Airflows and relative pressures within the system were constantly monitored and controlled by the computer system thus ensuring a uniform distribution and constant flow of fresh aerosol to each exposure port (breathing zone). The flow of air through each port was at least 0.7 L/min. This flow rate was considered adequate to minimise re-breathing of the test atmosphere as it is about twice the respiratory minute volume of a rat.
- Method of particle size determination: The particle size analysis of the generated test atmosphere was performed three times during the exposure period using a 7-stage cascade impactor of Mercer style (TSE Systems GmbH, Bad Homburg, Germany). During the exposure period samples were collected three times with one sample taken during the first hour of exposure, next in the second hour and last one during the last hour. Samples were collected from vacant animal exposure ports (representing the animal’s breathing zone) and were analysed. The collection substrates and the backup filter were weighed before and after sampling and the weight of test material, collected at each stage, calculated by this difference. The total amount collected for each stage was used to determine the cumulative amount below each cut-off point size. In this way, the proportion (%) of aerosol less than 0.55, 0.91, 1.55, 2.11, 3.51, 6.61 and 10.5 μm was calculated.
- Treatment of exhaust air: After passing through the animal’s breathing zone, used aerosol entered the outer cylinder from where it was exhausted through a suitable filter system. Atmosphere generation was therefore dynamic.
- Temperature and humidity in air chamber: 21.1 °C and 1.2 % (mean values.

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: The actual concentration of generated test atmosphere was measured gravimetrically at regular intervals during exposure by pulling a suitable, known volume of test atmosphere from the exposure chamber, through GF10 glass fibre filters. Sampling was performed shortly after chamber equilibration and then uniformly distributed, at approximately regular intervals. Samples were collected from a vacant animal exposure port (animals breathing zone). The amount of material collected on glass fibre filters was determined gravimetrically. The filter holder was opened before sampling and filter was weighed right before exposure. Immediately after sampling the filters were weighed again. Nominal concentration was calculated by dividing the total weight of test item disseminated into the test chamber by the total volume of air used during the same period.
- Particle size distribution and MMAD: An aerosol atmosphere was generated containing particles with a mass median aerodynamic diameter (MMAD) between 3 to 4 μm with a geometric standard deviation (GSD) in the range of 1.5 to 3.
- Time needed for equilibrium of exposure concentration before animal exposure: 11 minutes

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Measured gravimetrically at regular intervals during exposure by pulling a suitable, known volume of test atmosphere from the exposure chamber, through GF10 glass fibre filters (GE Healthcare Life Science, Whatman GmbH, Germany).

Duration of exposure:

4 h

Remarks on duration:

14-day observation period after 4 h exposure.

Concentrations:

3.38 mg/L (highest attainable concentration)

No. of animals per sex per dose:

10 animals, single dose (5 males / 5 females).

Control animals:

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing
1) Morbidity/mortality: Checks were made twice daily, early and late during the normal working day, for mortality and/or morbidity amongst the test animals.
2) Clinical Signs: As a minimum, individual, clinical observations were performed after one, two and three hours exposure whilst the animals were still restrained. Following exposure clinical observations were performed twice on the day of exposure (as soon as practicable after removal from restraint, and 1 hour after completion of the exposure), and then once daily for fourteen days. Cage-side observations included changes in the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. All observations were recorded.
3) Bodyweight: Individual bodyweights were recorded on the day of exposure day 0 (prior to exposure) and on days 1, 3, 7, 14.
- Necropsy of survivors performed: Yes. A gross necropsy was performed on all animals euthanised by exsanguination following intra-peritoneal injection of pentobarbital solution at the end of the 14-day observation period. A complete examination of the abdominal and thoracic cavities was made and special attention was given to the respiratory tract for macroscopic signs of irritancy or local toxicity. Any abnormalities were recorded.

Statistics:

The mean of the bodyweight and bodyweight gain were calculated by Excel spreadsheet software.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 3.38 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There was no mortality in the study.

Clinical signs:

other: Slight dyspnoea was noted during and/or after exposure in all exposed animals. In addition, red staining on the snout was noted in three animals shortly after exposure. All signs ceased from the day following exposure until the end of the observation.

Body weight:

Slight bodyweight loss/stagnation was observed in nine exposed animals on the day following exposure, which comes from the restrain procedure and has no toxicological relevance. Normal bodyweight gain was noted for all exposed animals from Day 1 until the end of observation period.

Gross pathology:

In the current study, no macroscopic abnormalities were found during the necropsy.

Interpretation of results:

other: not classified according to EU criteria

Conclusions:

Under the conditions of this study the 4-hour LC50 of the test material in rats was considered to be > 3.38 mg/L since no adverse effectd were noted at the highest attainable test concentration.

Executive summary:

The acute inhalation toxicity of the test material was assessed according to the standardised guidelines OECD 403, EC B.2 and OPPTS 870.1300, under GLP conditions.

During the study, groups of 5 males and 5 females were exposed to the maximum attainable concentration of the test material of 3.38 mg/L. The animals were exposed for 4 hours using a nose-only exposure system, followed by a 14-day observation period. The day of exposure was designated Day 0. Aerosol concentration was measured gravimetrically. The particle size distribution of the test aerosol was determined regularly during the exposure period. Clinical observations and bodyweights were recorded throughout the experiment and at the end of the scheduled period the surviving animals were euthanised and subjected to a gross examination post mortem.

The mean achieved concentration in the study was 3.38 mg/L. The mean mass median aerodynamic diameter (MMAD) was 3.72 μm with a geometric standard deviation (GSD) 2.84.

Under the conditions of the study, no mortality was observed. Slight dyspnoea was noted during and/or after exposure in all exposed animals. In addition, red staining on the snout was noted in three animals shortly after exposure, however all clinical signs ceased and all animals were symptom free from the day following exposure until the end of observation period. Slight bodyweight loss/stagnation was observed in nine exposed animals on the day following exposure, which comes from the restrain procedure and has no toxicological relevance. Normal bodyweight gain was noted for all exposed animals from Day 1 until the end of observation period. In the current study, no macroscopic abnormalities were found.

The 4-hour LC50 of the test material in rats was therefore considered to be > 3.38 mg/L since no adverse effectd were noted at the highest attainable test concentration.

Endpoint conclusion

Endpoint conclusion:: no adverse effect observed
Dose descriptor:: LC50
Value:: > 3.38 mg/L air
Physical form:: inhalation: aerosol
Quality of whole database:: The study was conducted according to standardised guidelines, in compliance with GLP, and as such was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

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:

10 April 2018 - 24 April 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

February 24 1987

Deviations:

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Stability: Stable under storage conditions
Storage conditions: The test material was put into an air-tight container and stored in the test material storage room at room temperature (acceptable range: from 10 °C to 30 °C).

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Cr1: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain rationale: This strain is established as experimental animals and commonly used in the general toxicity study and the testing facility has the historical control data.
- Age at study initiation: Males were seven weeks old, females were nine weeks old.
- Weight at study initiation: 243.7 - 251.8 g (males), 206.0 - 226.3 g (females)
- Housing: Animals were housed individually in stainless steel cages with mesh-floor (260 W x 380 D x 180 H mm).
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6 days
- Method of randomisation in assigning animals to test and control groups: The animals were allocated to groups using simple random sampling six days after the receipt. The animals were identified by painting using a red marker on the tail before the allocation , and by painting using a blue marker on the tail after the allocation. Cages were identified by individual labels and a rack was identified by indicating the study number, sex and dose level.

ENVIRONMENTAL CONDITIONS
- Temperature: 21 - 25 °C
- Humidity: 40 - 70 %
- Air changes: 10 - 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light per day (light on at 7:00 and off at 19:00).

Type of coverage:

semiocclusive

Vehicle:

olive oil

Details on dermal exposure:

TEST SITE
- Area of exposure: One day before test material application, an area on the back of each test animals, of approximately 5 x 10 cm, was clipped free of fur.
- Type of wrap if used: The dosing formulation was homogeneously applied to a non-woven gauze (5 x 5 cm) that was fixed to the test site by an elastic adhesive bandage.

REMOVAL OF TEST MATERIAL
- Twenty four hours after the application, the non-woven gauze and elastic adhesive bandage were removed and residual test material was removed using purified water and absorbent cotton.

TEST MATERIAL
- Concentration (if solution): test material was suspended in olive oil at a concentration of 20 % (w/v)
- Constant volume or concentration used: yes

VEHICLE
- Amount(s) applied: 10 mL/kg bw based on the body weight measured on the application day.
- Lot/batch no.: 701019

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Control animals:

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The clinical signs including the mortalities were observed. The animals were observed continuously for 10 minutes after the application, and observed once 30 minutes and three hours after the application, and daily thereafter. The animals were additionally observed after removal of the non woven gauze and elastic adhesive bandage. Body weights were measured at 0 (before application ), 7 and 14 days after the application with an electric balance (SARTORIUS).
- Necropsy of survivors performed: Yes. All animals were subjected to gross necropsy 14 days after the application. Application site, external surface of the body, all orifices, subcutis, cranial, thoracic, abdominal and pelvic cavities with their contents were observed.

Statistics:

Median lethal dose, LD50 value (mg/kg), is estimated according to the number of mortalities and moribundities.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortality occurred in any animals at a dose level of 2000 mg/kg bw.

Clinical signs:

other: Slight decreased spontaneous locomotion was observed in four males out of five and all five females between just after the application and three hours after the application. This sign disappeared in all animals one day after the application. Thereafter, n

Gross pathology:

No abnormalities were observed in any animals.

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

Under the conditions of the study the acute dermal toxicity of the test material to rats was considered to be > 2000 mg/kg bw.

Executive summary:

The acute dermal toxicity of the test material was investigated in accordance with the standardised guideline OECD 402, under GLP conditions.

The test material was suspended in olive oil and applied over the dorsal area of Crl:CD(SD) rats after hair of the animals was clipped. The applied area was covered with non woven gauze and elastic adhesive bandage for 24 hours. The dose level was set at 2000 mg/kg bw which is the limited dose in the test method. Five males at seven weeks old and five females at nine weeks old were used for the application. Clinical signs were observed daily for 14 days and body weights were measured 0 (before administration), 7 and 14 days after the administration. The animals were subjected to a gross necropsy 14 days after the administration.
No mortalities or moribundities occurred. No abnormalities associated with the application of the test material were observed in the general clinical observation, body weights measurements or gross necropsy.

Under the conditions of the study the acute dermal toxicity of the test material to rats was therefire considered to be > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:: no adverse effect observed
Dose descriptor:: LD50
Value:: > 2 000 mg/kg bw
Quality of whole database:: The study was conducted according to standardised guidelines, in compliance with GLP, and as such was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

Additional information

Acute oral toxicity (Appl 2017)

The acute oral toxicity of the test material was investigated according to the standardised guidelines OECD 423, EU Method B.1.Tris and EPA OPPTS 870.1100, and under GLP conditions, following the Acute Toxic Class Method. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The acute oral LD50 of the test material was therefore determined to be > 2000 mg/kg bw in female rats.

Acute inhalation toxicity (Nagy 2021)

The acute inhalation toxicity of the test material was assessed according to the standardised guidelines OECD 403, EC B.2 and OPPTS 870.1300, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The mean achieved concentration in the study was 3.38 mg/L. The mean mass median aerodynamic diameter (MMAD) was 3.72 μm with a geometric standard deviation (GSD) 2.84.

The 4-hour LC50 of the test material in rats was therefore considered to be > 3.38 mg/L since no adverse effectd were noted at the highest attainable test concentration.

Acute dermal toxicity (Tsubokura 2018)

The acute dermal toxicity of the test material was investigated in accordance with the standardised guideline OECD 402, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The test material was suspended in olive oil and applied over the dorsal area of Crl:CD(SD) rats after hair of the animals was clipped. The applied area was covered with non woven gauze and elastic adhesive bandage for 24 hours. The dose level was set at 2000 mg/kg bw which is the limited dose in the test method. Five males at seven weeks old and five females at nine weeks old were used for the application. Clinical signs were observed daily for 14 days and body weights were measured 0 (before administration), 7 and 14 days after the administration. The animals were subjected to a gross necropsy 14 days after the administration. No mortalities or moribundities occurred. No abnormalities associated with the application of the test material were observed in the general clinical observation, body weights measurements or gross necropsy.

Under the conditions of the study the acute dermal toxicity of the test material to rats was therefire considered to be > 2000 mg/kg bw.

Justification for classification or non-classification

The substance does not require classification in accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008.

Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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