Dilutetium oxide silicate

Endpoint summary

Description of key information

Acute oral toxicity

The oral LD50 for rats was found to be > 2000 mg/kg bw in the key study, which was performed according to the acute toxic class method (OECD guideline 423) and conform GLP requirements (Zelenák, 2017a). This study was considered reliable without restrictions (Klimisch 1). Based on these results, the test substance is considered not classified as acute oral toxicant.

Acute inhalation toxicity

In a reliable acute inhalation toxicity study performed according to OECD guideline 403, no deaths occurred in two groups of 5 rats exposed for 4 hours to the maximum feasible aerosol atmosphere concentration that could be tested, namely 4.03 mg/L. This key study (Klimisch 1) was performed conform GLP requirements (Tóth, 2018). Based on the 4-h LC50 value > 4.03 mg/L and relevant data for other rare earth compounds, the substance is considered not to be classified as acute toxicant via inhalation.

Acute dermal toxicity

The acute oral LD50 is greater than 2000 mg/kg bw and no systemic effects or macroscopic abnormalities were observed in the study available for this endpoint. According to Annex VIII, column 2 of the REACH Regulation (revision May 2016), acute dermal toxicity can be waived if the substance under consideration is not classified as acute oral toxicant or as STOT SE, and no systemic effects have been observed in in vivo studies with dermal exposure. The latter criterion (in vivo skin sensitisation study, Tarcai, 2017) is also fulfilled.

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:

25 October 2016 - 20 January 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:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: On the day of administration, the test item was freshly formulated at a concentration of 200 mg/mL (anhydrous form) with the vehicle.
- A correction factor of 1.05 was applied when preparing the dose formulations (to correct for the water content of the test item).

FORM AS APPLIED IN THE TEST (if different from that of starting material): formulation with 1% methylcellullose at a concentration of 200 mg/mL

Species:

rat

Strain:

Wistar

Remarks:

Crl:(WI)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: young healthy adult rats, 10 weeks old
- Weight at study initiation: 210 - 256 g. Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: The night before treatment the animals were fasted for a maximum of 16 hours. Food, but not water, was withheld overnight. Food was replaced 3 hours after treatment.
- Housing: Group caging (3 animals/cage) in type II. polypropylene/polycarbonate cages. “Lignocel 3/4-S Hygienic Animal Bedding” and “Arbocel crinklets natural” nest building material produced by J. Rettenmaier & Söhne GmbH & Co.KG (D-73494 Rosenberg, Germany) were available to animals during the study.
- Diet (e.g. ad libitum): ad libitum; ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by Ssniff Spezialdiäten GmbH, D-59494 Soest Germany (batch number: 141 8884, expiry date: January 2017 and batch number: 278 5652, expiry date: November 2016)
- Water (e.g. ad libitum): ad libitum; tap water from the municipal supply, as for human consumption from a 500-mL bottle
- The food is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. Water quality control analysis was performed once every three months and microbiological assessment was performed monthly, by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József A. u. 36., Hungary).
- Acclimation period: 26-27 days before start of treatment under laboratory conditions. Health inspection was performed at arrival of the animals. Only healthy animals were used for the test. The health status was certified by the veterinarian.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3ºC
- Humidity (%): 30-70%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light, lighting period from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES:
- From: 2016-10-25 To: 2016-11-08 (females no. 2954, 2955, 2956)
- From: 2016-10-26 To: 2016-11-09 (females no. 2957, 2958, 2959)

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

aqueous solution of methylcellulose at 1%

Details on oral exposure:

VEHICLE (1% methylcellulose)
- Concentration in vehicle: 200 mg/L
- Justification for choice of vehicle: The selection of the vehicle was based on trial formulations with the test item. In order of preference, the recommended vehicles were the following: distilled water, 0.5 or 1% methylcellulose or carboxymethylcellulose, PEG 400, corn oil, sunflower oil or DMSO. 1% methylcellulose appeared to be most suitable.
- Lot/batch no. (if required): S11122

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): Test item was freshly formulated on the day of administration. To limit the impact, the formulations were used within 4 hours after adding the vehicle to the test item and the test item preparation was performed with approved procedures and documented in detail. The formulation was homogenised to visually acceptable levels and was stirred up to finishing the treatment to ensure sufficient homogeneity.

- Rationale for the selection of the starting dose: The initial dose level was selected by the Study Director 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. The limit dose (= starting dose level) for this study was 2000 mg/kg bw.

Doses:

2000 mg/kg

No. of animals per sex per dose:

2 groups; 3 females/group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
*Clinical signs: Animals were observed individually after dosing at 30 minutes, then 1, 2, 3, 4 and 6 hours after the treatment and once each day in the morning for 14 consecutive days thereafter.
*Individual observations were performed on 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.
*Body weight: The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
- Necropsy of survivors performed: Yes, all animals were subjected to a necropsy and a macroscopic examination. The animals were exsanguinated after verification of narcosis following an injection of pentobarbital sodium (Euthanimal 40%; Lot No.: 1409236-06, Expiry Date: September 2017, Produced by: AlfasanNederland BV, Woerden, The Netherlands). After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross macroscopic changes were recorded for each animal.

Statistics:

No statistical analysis was performed.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks:

anhydrous lutetium oxide silicate

Mortality:

None

Clinical signs:

other: None

Gross pathology:

There was no evidence of macroscopic observations at a dose level of 2000 mg/kg bw.

Other findings:

No data

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, the acute oral LD50 value of lutetium oxide silicate was found to be above 2000 mg/kg bw in female Crl:(WI) rats. According to these results, lutetium oxide silicate needs not to be classified according to CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

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:

2 February 2017 - 1 August 2018

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:

adopted: 07 September 2009

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Version / remarks:

adopted: 07 September 2009

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

August 1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

yes

Specific details on test material used for the study:

Treatment of test material prior to testing: The test item was used as supplied.

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI from SPF colony

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Model and Services, Germany GmbH (Sandhofer Weg 7, D-97633, Sulzfeld, Germany)
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation:
• Sighting exposure (Group 0.1): approximately 10 weeks old
• Main study (Group 1): approximately 8 weeks old
- Weight at study initiation:
• Sighting exposure (Group 0.1): 380 g (male) and 228 g (female)
• Main study (Group 1): 401-416 g (males) and 237-258 g (females)
- Fasting period before study: no data
- Housing: Group caging (5 animals, by sex, per cage), individual caging during the sighting study; polycarbonate solid floor cages (type II or type III) with stainless steel mesh lids
- Diet (e.g. ad libitum): ad libitum, the animals were provided with ssniff SM R/M “Autoclavable Complete Feed for Rats and Mice – Breeding and Maintenance” (ssniff Spezialdiäten GmbH, D-59494 Soest Germany)
- Water (e.g. ad libitum): ad libitum, tap water fit for human consumption
- Acclimation period: 22 days (sighting group), 5 days (main study)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.5 – 26.5°C
- Humidity (%): 23 – 79%
- Air changes (per hr): at least 15 air exchanges per hour
- Photoperiod (hrs dark / hrs light): 12 hours of continuous artificial light in each twenty-four hour period (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):

3.52 µm

Geometric standard deviation (GSD):

2.4

Remark on MMAD/GSD:

inhalable fraction (% < 4 µm): 58.1%

Details on inhalation exposure:

TECHNICAL TRIALS
- Prior to animal exposures, test material atmospheres were generated within the exposure chamber. During these technical trials, air-flow settings, test material input rates and test item formulation of the material were varied to achieve the required aerosol concentration of particles with a mass median aerodynamic diameter (MMAD) between 1 to 4 µm and a geometric standard deviation (GSD) in the range of 1.5 to 3.0. Measurements of aerodynamic particle size were performed from the animal’s breathing zone using a cascade impactor.
After the technical trials, a new batch was used in the in-life phase, as the amount of the first batch was not enough to perform the study.

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- The animals were exposed, nose-only, to an atmosphere of the test item using a TSE Rodent Exposure System (TSE Systems GmbH, Bad Homburg, Germany). This system comprises two concentric anodised aluminium chambers and a computer control system incorporating pressure detectors and mass flow controllers.
- 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.
- Method of holding animals in the test chamber: The animals were held in polycarbonate restraint tubes located around the chamber which allowed only the animal’s nostrils to enter the exposure port.
- Source and rate of air: Compressed air was supplied by means of an oil-free compressor and passed through a suitable filter system prior to introduction to the nebuliser. The flow of air through each port was at least 0.5 L/min. This flow rate was considered adequate to minimise re-breathing of the test atmosphere as it is approximately twice the respiratory minute volume of a rat.
- System of generating particulates/aerosols: The test item was aerosolised using PALAS RBG1000 (Palas GmbH, Karlsruhe, Germany; Serial Number: 1717) located at the top of the exposure chamber. Compressed air was supplied by means of an oil-free compressor passed through a suitable filter system prior to introduction to the aerosol generator.
- Method of particle size determination: The particle size of the test atmosphere was determined three times during the exposure period using a 7-stage impactor of Mercer style (TSE Systems GmbH, Bad Homburg, Germany). Such devices employ an inertial separation technique to isolate particles in the discrete aerodynamic size ranges. Samples were taken from an unoccupied exposure port (representing the animal’s breathing zone). The collection substrates and the backup filter were weighed before and after sampling and the weight of test item, 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 < 0.550, 0.550, 0.960, 1.550, 2.105, 3.555, 6.655 and 10.550 µm was calculated. From these data, using the software supplied with the impactor (TSE Systems GmbH, Bad Homburg, Germany), the Mass Median Aerodynamic Diameter (MMAD), and Geometric Standard Deviation (GSD) were calculated. In addition, the proportion (%) of aerosol less than 4 µm (considered to be the inhalable portion) was determined.
- 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 in test chamber: 19.8-22.4°C (mean: 21.4°C).

TEST ATMOSPHERE
- The test atmosphere was sampled at regular intervals during the exposure period. Samples were taken from an unoccupied exposure port (representing the animal’s breathing zone) by pulling a suitable volume of test atmosphere through weighed GF10 glass fibre filters (Whatman®, Whatman GmbH, Germany, Ref./Lot no.: A10256986, A10058746).
- The difference in the pre and post sampling weights, divided by the volume of atmosphere sampled, was equal to the actual achieved test atmosphere concentration. The nominal concentration was calculated by dividing the mass of test material disseminated into the chamber by the total volume of air that flowed through the chamber during the same period.

CLASS METHOD
- Rationale for the selection of the starting concentration: maximal technically achievable concentration

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetrical determination

Duration of exposure:

4 h

Concentrations:

A sighting exposure was performed first, where a maximum achievable test atmosphere of dilutetium oxide silicate at a 4.62 mg/L concentration was tested on single animals of both sexes (Group 0.1).
As both animals survived the treatment, the main study group (Group 1) of 5 male and 5 female Crl:WI Wistar strain rats were exposed to an aerosol atmosphere of dilutetium oxide silicate at the maximum feasible concentration of 4.03 mg/L.

No. of animals per sex per dose:

sighting exposure: 1 male and 1 female
main study: 5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
*Morbidity/mortality: Animals were checked hourly during exposure, 1 hour after exposure and twice daily (early and late in the working day) during the 14-day observation period for morbidity and/or mortality.
*Clinical signs: All animals were observed for clinical signs at hourly intervals during exposure whilst the animals were still restrained. Following exposure, clinical observations were performed twice on the day of exposure (following removal from the restrainer and approximately one hour after completion of the exposure) and subsequently once daily for 14 days.
Observations included changes in the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somato-motor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
*Body weight: Individual body weights were recorded prior to treatment on the day of exposure (on Day 0) and on Days 1, 3, 7 and 14.
- Necropsy: At the end of the 14-day observation period, the surviving animals were sacrificed by exsanguination under anaesthesia (intra-peritoneal injection of pentobarbital solution – Euthanimal 40%; Lot No.: 1609291-03; Expiry: October 2019; Produced by Alfasan International B. V., Woerden, Netherlands) and gross macroscopic examination was performed.
All rats were subject to a gross necropsy which included a detailed examination of the abdominal and thoracic cavities. Special attention was given to the respiratory tract for macroscopic signs of irritancy or local toxicity.

Statistics:

No statistics performed.

Preliminary study:

A sighting exposure was performed first, where a maximum achievable test atmosphere of dilutetium oxide silicate at a 4.62 mg/L concentration was tested on single animals of both sexes (Group 0.1). Both animals survived the treatment.
The mean achieved atmosphere concentrations in this sighting study was 4.62 mg/L. The mass median aerodynamic diameter (MMAD) was 3.39 µm with a geometric standard deviation (GSD) of 2.22.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.03 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 4.03 mg/L was the maximum achievable test concentration

Mortality:

There was no mortality in the study.

Clinical signs:

other: Red-brown staining was commonly recorded on the day of the exposure, which was considered to be related to the restraint and exposure procedures but not to be toxicologically significant. The following observations were considered to be related to exposur

Body weight:

In Group 0.1, no or minimal body weight loss (1.3%) was recorded on the day of treatment. In the observation period, normal body weight gain was recorded in both animals.
In Group 1, no or slight body weight loss (max. of 8.8%) was recorded after the treatment. In the observation period from Day 3, normal body weight gain was recorded in all animals.

Gross pathology:

A single four hours nose-only exposure of dilutetium oxide silicate to Wistar Crl:WI rats dosed at 4.62 mg/L (sighting exposure) or 4.03 mg/L (main study) was associated with test item-related enlargement of lung-associated lymph nodes.

Other findings:

No data

Test atmosphere concentration:

The test atmosphere concentration was sampled in the breathing zone during the 4-hour exposure period 17 times at approximately equal intervals during both parts of the study.

The mean achieved actual concentrations based on the analysis of these filter samples and nominal concentrations are presented in the table below.

Mean achieved actual and nominal aerosol concentration

Part of Study	Target Concentration (mg/L)	Mean Achieved Concentration (mg/L)	Standard Deviation of Achieved Concentration (mg/L)	Nominal Concentration (mg/L)
Sighting exposure: Group 0.1	Maximum attainable	4.62	0.33	61.97
Main study: Group 1	Maximum attainable	4.03	0.55	65.26

Particle size analysis:

Analysis of the particle size distribution of the aerosol at the animals’ breathing zone demonstrated that during both parts of the study (sighting exposure and main study) the test atmosphere was respirable to the animals. The mean values of the particle size distribution parameters calculated from three samples of each exposure are presented in the following table.

Mean achieved particle size distribution data (MMAD and GSD)

Part of Study	Target Concentration (mg/L)	Mean Mass Median Aerodynamic Diameter (MMAD) (mm)	Geometric Standard Deviation (GSD)	Inhalable Fraction (% < 4 mm)
Sighting exposure: Group 0.1	Maximum attainable	3.39	2.22	58.1
Main study: Group 1	Maximum attainable	3.52	2.40	55.7

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, no death occurred in a group of 10 Wistar Crl:WI rats (main study) that were exposed to a maximum achievable test atmosphere concentration of 4.03 mg/L for 4 hours. The acute inhalation median lethal concentration (LC50) of dilutetium oxide silicate in Wistar Crl:WI rats was therefore considered to be above 4.03 mg/L. Based on these results and on relevant experimental data from other rare earth compounds, the test substance is considered not to be classified as acute toxicant via inhalation according to the CLP Regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

4 030 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

One reliable study is available on the acute oral toxicity of lutetium oxide silicate in rats. This study was performed according to the acute toxic class method (OECD guideline 423) and conform GLP requirements (Zelenák, 2017a). In this study, 6 female Wistar Crl:(WI) rats were dosed on a single occasion with the test substance formulated in 1% methylcellulose at 2000 mg/kg bw. During the subsequent 14-day observation period, no deaths or clinical signs were observed. Body weight gain and macroscopic examination at necropsy demonstrated no deviations. The LD50 was therefore > 2000 mg/kg bw. This study is considered reliable (Klimisch 1) and is the key study for endpoint coverage.

Acute inhalation toxicity

One reliable study was performed to assess the acute inhalation toxicity of lutetium oxide silicate (Tóth, 2018).

The study was performed in multiple steps. Initially, a study according to OECD guideline 436 was planned, but as the limit concentration of 5.0 mg/L was technically not feasible, the study was performed according to OECD guideline 403.

A sighting exposure was performed first, where a maximum achievable test atmosphere of lutetium oxide silicate at a 4.62 mg/L concentration was tested on single animals of both sexes (Group 0.1). As both animals survived the treatment, the main study group (Group 1) of 5 male and 5 female Crl:WI Wistar strain rats were exposed to an aerosol atmosphere of lutetium oxide silicate at the maximum feasible concentration of 4.03 mg/L.

In all study phases, the animals were exposed to the test atmosphere for 4 hours using a nose-only exposure system. No control group was exposed in this study.

Under the experimental conditions of this study, no deaths occurred in the group of 10 Wistar Crl:WI rats (main study) that were exposed to a maximum achievable test atmosphere concentration of 4.03 mg/L for 4 hours. The acute inhalation median lethal concentration (LC50) of lutetium oxide silicate in Wistar Crl:WI rats was therefore considered to be above 4.03 mg/L.

 

Acute dermal toxicity

The acute oral LD50 is greater than 2000 mg/kg bw and no systemic effects or macroscopic abnormalities were observed in this study (Zelenák, 2017a). According to Annex VIII, Section 8.5, column 2 of the REACH Regulation (revision May 2016), acute dermal toxicity can be waived if the substance under consideration is not classified as acute oral toxicant or as STOT SE, and no systemic effects have been observed in in vivo studies with dermal exposure. The latter criterion is also fulfilled (in vivo skin sensitisation study (GPMT), Tarcai, 2017).

Justification for classification or non-classification

Acute oral toxicity

The LD50 is greater than 2000 mg/kg bw and therefore lutetium oxide silicate is considered not classified as acute oral toxicant according to the CLP Regulation.

Acute inhalation toxicity

The LC50 is greater than 4.03 mg/L, which was the maximum achievable test atmosphere concentration in this study. As no mortality occurred at this concentration, the substance needs not to be classified.

Acute dermal toxicity

No acute dermal toxicity study is available for lutetium oxide silicate. However, based on the acute oral LD50 being > 2000 mg/kg bw, the absence of systemic effects or macroscopic abnormalities in the acute oral study (no STOT SE classification required), and the fact that no systemic effects have been observed in in vivo studies involving dermal exposure (in vivo skin sensitisation study, GPMT), the substance can be safely concluded not to be classified as acute dermal toxicant.