1-chloro-N,N-diethyl-1,1-diphenyl-1-(phenylmethyl)phosphoramine

Endpoint summary

Description of key information

Oral: LD50 = 123 mg/kg bw in an OECD 401 study on rats.
Inhalation: LC50/4h = 50 mg/m3 in an OECD 403 study on rats.
Dermal: LD50 > 2000 mg/kg bw in an EU B.3 study on rats. One female rat died during the study. No general clinical signs were seen in the surviving animals, but they showed erythema, edema, and crusts at the application site.

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 June 1994 to July 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP- and OECD TG-compliant study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS: Sprague Dawley Crl: CD (SD) BR rats
- Source: Charles River Italia S.p.A.
- Age at study initiation: 7/9 weeks
- Weight at study initiation: Males: 225 - 250 g ; Females: 200 - 225 g
- Fasting period before study: 16 hours
- Housing: 5 animals/sex/cage in T11C air-conditioned room, grill cage 40.5x38.5x18 cm with stainless feeder
- Diet (e.g. ad libitum): ad libitum, GLP 4RF1 Charles River Italia's feed licensee Mucedola s.r.l., Settimo Milanese
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 °C
- Humidity (%): 55 +/- 10
- Air changes (per hr): 20/hours filtered on HEPA 99.97%
- Photoperiod (hrs dark / hrs light): 12 hour cycles (light: 7am - 7 pm)

IN-LIFE DATES: From: june 15, 1994 To: july 1, 1994

Route of administration:

oral: gavage

Vehicle:

other: Deionized water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 6.7, 10, 15 mg/ml

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

67 mg/kg, 100 mg/kg, 150 mg/kg

No. of animals per sex per dose:

67 mg/kg : 5 Males and 5 females
100 mg/kg: 5 males
150 mg/kg: 5 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 30 min, 2, 4 ,6 hours post-dosing, then twice a day
- Necropsy of survivors performed: yes
- Other examinations performed:
clinical signs: daily
body weight: day 1, 3, 8 and 14
organ weights, histopathology, other: No

Statistics:

Method of Probit (Bliss-Finney) - AP. Rosiello et al., J. Tox. and Env. Health, 3:797-809, 1977

Sex:

male/female

Dose descriptor:

LD50

Effect level:

123 mg/kg bw

95% CL:

100.4 - 150.2

Remarks on result:

other: Slope of the mortality curve: 4.33

Mortality:

Male: 67 mg/kg bw; Number of animals: 5; Number of deaths: 0
Male: 100 mg/kg bw; Number of animals: 5; Number of deaths: 1
Male: 150 mg/kg bw; Number of animals: 5; Number of deaths: 4
Female: 67 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: Signs of toxicity related to dose levels: Piloerection, hunched posture and diarrhea were observed in animals treated at 67 mg/Kg starting from 2 hours and lasting up to 24 hours after the administration. Animals treated at 100 and 150 mg/Kg showed th

Gross pathology:

Effects on organs: Animals which died showed congestion of the lungs, kidneys, stomach, intestine and thymus and also paleness of the liver and thinning walls with catharral or catharral-hemorrhagic content in the intestine. At the autopsy carried out at the end of the observation period no appreciable macroscopic findings were evident in any treated rat.

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In conclusion, the LD50 to rats was found to be 123 mg/kg.
From this value the substance is to be classified as toxic if swallowed according to the CLP Regulation (EC) No. 1272/2008.

Executive summary:

The acute oral toxicity of the test item GM102E was investigated in a study performed on Sprague Dawley rats at concentrations of 67, 100 and 150 mg/kg.

The test was performed according to OECD guideline 401 and in compliance with GLP.

The test item was administered by gavage to 5 male rats per dose and a further group of 5 females was tested at 67 mg/kg of GM102E. The test item was dissolved in deionized water before administration and the administration volume was kept constant at 10 ml/kg b.w. in all the groups.

All rats were treated after a 16 hours fasting period. The animals were weighed twice before treatment (at randomization and on day 1 just before the study) and on days 3, 8 and 14 after exposure period. They were clinically observed for 14 days following treatment. On day 15 all treated rats were killed by excision of the femoral arteries, after i.p. overdosage anesthesia with 5% sodium pentobarbital. Animals which died and animals killed at the end of the study were submitted to a thourough autopsy.

Piloerection, hunched posture and diarrhea were clinically observed in animals treated at the lowest dose (67 mg/kg) starting from 2 hours and lasting up to 24 hours after the test item administration. Animals treated at the highest doses (100 and 150 mg/kg) showed the same clinical signs and, in addition, sedation and/or hypoactivity and sporadic cases of shallow breathing, chromodacryorrhea and pallor of the skin and apparent mucosae. These signs started from 30 minutes – 4 hours and lasted up to 6 hours – day 3 of the study. Recovery of all surviving rats was achieved within days 2 – 4 of the study.

Body weight gain resulted unaffected by treatment in animals treated at the lowest dose. Surviving male rats treated at 100 and 150 mg/kg showed decrease in body weight or low body weight gain at the day 3 weighing. Body weight gain returned to normal at the subsequent recordings.

At the autopsy, animals which died showed congestion of the lungs, kidnays, stomach, intestine and thymus and also paleness of the liver and thinning walls with catharral or catharral-hemorrhagic content in the intestine.

At the autopsy carried out at the end of the observation period no appreciable macroscopic findings were evident in any treated rat.

One male treated at 100 mg/kg and 4 males treated at 150 mg/kg died within 2 hours of treatment. No animals treated at 67 mg/kg died. The LD50 was calculated to be 122.8 mg/kg with 95% confidence limits of 100.4 – 150.2 mg/kg.

Based on these results and according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP), GM102E should be classified as toxic by ingestion (Acute tox. Category 3, H301).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

123 mg/kg bw

Quality of whole database:

Two reliable studies are available. One key study was performed according to OECD guideline 401 and in compliance with GLP. The second study was reported as a supporting study of reliabilty 2 as no specific guideline was followed.

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:

18 September 2014 - 05 January 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP- and OECD TG-compliant 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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 12 weeks old
- Weight at study initiation: Males: 312-374 g / Females: 210 - 235 g
- Fasting period before study: No
- Housing: Group housing of five animals per sex per cage in labelled Makrolon cages (type IV; height 18 cm) containing sterilised sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom)
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) except during exposure to the test substance
- Water (e.g. ad libitum): Free access to tap water except during exposure to the test substance
- Acclimation period: at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24
- Humidity (%): 40 to 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 18 September 2014 To: 24 October 2014

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

For the 0.4 mg/L exposure group, the test substance was administered to a stream of pressurized air using a combination of a brush feeder and a micronizing jet mill (Bernstein, D.N., Aerosols, pp 721- 723, 1984). A vibrator was attached to the brush feeder. The aerosol was passed through a series of three vertical cyclones, allowing larger particles to settle, and subsequently passed through the exposure chamber (Appendix 1, Figure 1). The total mean airflow was 79 L/min.

For the 0.06 mg/L exposure group, the test substance was administered to a stream of pressurized air using a combination of a spiral feeder (Randcastle Extrusion Systems, Cedar Grove, NJ, USA) and air mover (AIR-VAC, Milford, CT, USA). A vibrator was attached to the spiral feeder. The aerosol was passed through a series of three vertical and one horizontal cyclone, allowing larger particles to settle, and subsequently diluted with pressurized air before it entered the exposure chamber (Appendix 1, Figure 1). The mean total airflow was 106 L/min.

From the exposure chamber the test atmosphere was passed through a filter before it was released to the exhaust of the fume hood.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

A total of 22 representative samples were taken for determination of the actual concentration during exposure at 0.4 and 0.06 mg/L, respectively.

Duration of exposure:

4 h

Concentrations:

0.06 and 0.4 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Mortality/Viability: Twice daily. Animals showing pain, distress or discomfort, which was considered not transient in nature or was likely to become more severe, were sacrificed for humane reasons based on OECD guidance document on humane endpoints (ENV/JM/MONO/ 2000/7). The time of death was recorded as precisely as possible.

Clinical signs - During exposure: Three times during exposure for mortality, behavioural signs of distress and effects on respiration.

Clinical signs - After exposure: On Day 1, one and three hours after exposure 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: Maximum grade 4: grading slight (1) to very severe (4) Maximum grade 3: grading slight (1) to severe (3) Maximum grade 1: presence is scored (1).

Body weights: Days 1 (pre-administration), 2, 4, 8 and 15.

Necropsy: The moribund animals and animals surviving to the end of the observation period were sacrificed by an intraperitoneal injection with Euthasol® (AST Farma BV, Oudewater, The Netherlands). All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded. Particular attention was given to any changes in the respiratory tract.

Statistics:

No statistical analysis was performed.

Preliminary study:

Not applicable

Sex:

male/female

Dose descriptor:

LC50

Effect level:

>= 0.05 - < 0.5 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

At 0.4 mg/L, three males and two females were found dead during or within 1 hour after exposure. The remaining two males and three females were sacrificed for ethical reasons due to their poor clinical condition within 2.5 hours post-exposure.
At 0.06 mg/L, no mortality occurred.

Clinical signs:

other: At 0.4 mg/L, slow breathing, laboured respiration and excessive loss of faeces and urine was seen for the animals during exposure (not presented in the table). Lethargy, hunched posture, rales, gasping, laboured respiration, piloerection and hypothermia w

Body weight:

Overall body weight gain in surviving males and females was within the range expected for rats of this strain and age used in this type of study and was therefore considered not indicative of toxicity.

Gross pathology:

At 0.4 mg/L, macroscopic post mortem examination revealed abnormalities of the lungs (several dark red foci, dark red discolouration of the right cranial lobe, dark red colouration) for four animals sacrificed for ethical reasons. No abnormalities were seen for the remaining animals sacrificed or found dead.
At 0.06 mg/L, no abnormalities were found at macroscopic examination of the animals.

Test atmosphere characterization:

Concentration:

For the 0.4 mg/L exposure group, the time-weighted mean actual concentration was 0.42 ± 0.02 mg/L. The nominal concentration (amount of test substance used divided by the volume of pressurized air used) was 2.16 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 19%.

The concentration measurements equally distributed over time showed it was difficult to maintain a continued stable exposure level. The generation was interrupted several times in order to remove test substance deposits from the system. The generation time was elongated with 55 minutes resulting in an actual exposure time of 257 minutes. Since the actual exposure level was calculated based on the actual exposure, the achieved exposure was considered representative for one continued exposure to 0.42 mg/L for 4 hours.

For the 0.06 mg/L exposure group, the time-weighted mean actual concentration was 0.06 ± 0.002 mg/L. The nominal concentration (amount of test substance used divided by the volume of pressurized air used) was 2.64 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 2%.

The concentration measurements equally distributed over time showed it was difficult to maintain a continued stable exposure level. The generation was interrupted twice in order to remove test substance deposits from the air mover. The generation time was elongated with 8 minutes resulting in an actual exposure time of 251 minutes. Since the actual exposure level was calculated based on the actual exposure, the achieved exposure was considered representative for one continued exposure to 0.06 mg/L for 4 hours.

 

The actual concentrations deviated from the target concentrations of 0.5 and 0.05 mg/L but based on the results the interpretation and classifications were not affected.  

 

Particle size:

The Mass Median Aerodynamic Diameter (MMAD) and geometric standard deviation (gsd) were determined twice during the exposure period. At 0.4 mg/L, the MMAD was 3.1µm (gsd 1.9) and 3.6 µm (gsd 2.1). At 0.06 mg/L, the MMAD was 2.8 µm (gsd 1.5) and 3.0 µm (gsd 1.7).

Interpretation of results:

Category 2 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The inhalatory LC50, 4h value of GM102E in Wistar rats was established to be within the range of 0.05 – 0.5 mg/L.

Based on these results and according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP), GM102E needs to be classified as Acute Tox. Category 2 by inhalation and labeled as H330: Fatal if inhaled.

Executive summary:

GM102E was administered as an aerosol by inhalation (nose only) for 4 hours to two groups of five male and five female Wistar rats at a concentration of 0.4 and 0.06 mg/L, respectively. Animals were subjected to daily clinical observations and determination of body weights on Days 1, 2, 4, 8 and 15.Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

For the 0.4 mg/L exposure group, the time-weighted mean actual concentration was 0.42 ± 0.02 mg/L. The nominal concentration(amount of test substance used divided by the volume of pressurized air used) was 2.16 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 19%.

For the 0.06 mg/L exposure group, the time-weighted mean actual concentration was 0.06 ± 0.002 mg/L. The nominal concentration was 2.64 mg/L resulting in a generation efficiency of 2%. The concentration measurements equally distributed over time showed that the concentrations were sufficiently stable in order to classify GM102E.  

 

The actual concentrations deviated from the target concentrations of 0.5 and 0.05 mg/L but based on the results the interpretation and classifications were not affected.  

 

The Mass Median Aerodynamic Diameter (MMAD) and geometric standard deviation (gsd) were determined twice during the exposure period.

At 0.4 mg/L, the MMAD was 3.1 µm (gsd 1.9) and 3.6 µm (gsd 2.1).

At 0.06 mg/L, the MMAD was 2.8 µm (gsd 1.5) and 3.0 µm (gsd 1.7)

 

At 0.4 mg/L, three males and two females were found dead during or within 1 hour after exposure. The remaining two males and three females were sacrificed for ethical reasons due to their poor clinical condition within 2.5 hours post-exposure.

At 0.06 mg/L, no mortality occurred.

 

At 0.4 mg/L, slow breathing, laboured respiration and excessive loss of faeces and urine was seen for the animals during exposure. Lethargy, hunched posture, rales, gasping, laboured respiration, piloerection and hypothermia were seen for the animals post-exposure on Day 1.

At 0.06 mg/L, fast breathing was seen for the animals during exposure. After exposure, hunched posture and piloerection were seen for the animals. One male showed laboured respiration. The animals had recovered from the clinical signs between Days 2 and 3.

 

Overall body weight gain in surviving males and females was within the range expected for rats of this strain and age used in this type of study and was therefore considered not indicative of toxicity.

At 0.4 mg/L, macroscopic post mortem examination revealed abnormalities of the lungs (several dark red foci, dark red discolouration of the right cranial lobe, dark red colouration) for four animals sacrificed for ethical reasons. No abnormalities seen for the remaining animals sacrificed or found dead.

At 0.06 mg/L, no abnormalities were found at macroscopic examination of the animals.

 

The inhalatory LC_{50, 4h}value of GM102E in Wistar rats was established to be within the range of 0.05 – 0.5 mg/L.

Based on these results and according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP), GM102E needs to be classified as Acute Tox. Category 2 by inhalation and labeled as H330: Fatal if inhaled.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

50 mg/m³ air

Quality of whole database:

Only one reliable study available.

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:

March 1993 to April 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Standardised method following EC Dir 84/449, although some details are missing in the report.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Annex V B.3, Dir. 84/449/EEC

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Strain: Sprague Dawley Crl: CD (SD) BR rat
- Source: Charles River Italia S.p.A.
- Age at study initiation: 7-9 weeks
- Weight at study initiation: Males: 225-250g ; Females: 200 - 225 g
- Fasting period before study:
- Housing: individual grill cages
- Diet (e.g. ad libitum): ad libitum, except fasting period prior to dosing
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C+/2 2
- Humidity (%): 55% +/- 10
- Air changes (per hr): 20/hour filtered on HEPA 99.97%
- Photoperiod (hrs dark / hrs light): 12 hour cycle (light 7 am-7 pm)

IN-LIFE DATES: From: 25 March 1993 To: 9 April 1993

Type of coverage:

semiocclusive

Vehicle:

not specified

Remarks:

No details provided in the report.

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal surface
- % coverage: 10%
- Type of wrap if used: porous gauge dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing. After exposure period, residual substance was wiped off.
- Time after start of exposure: 24 hours

TEST MATERIAL
- For solids, paste formed: No details were provided in the report, but the method followed (EC Dir. Annex V, B.3, 94/449) indicates that the powder should be moistened with water.

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 Males and 5 females/dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
clinical signs observed at 30 min, 2, 4, 6 hours post dosing, then twice daily
weight: twice before dosing (at randomisation and on day 1 before treatment), then on day 8 and 15

- Necropsy of survivors performed: yes (gross pathology)
- Other examinations performed:
clinical signs: yes
body weight: yes
organ weights: no
histopathology: no

Statistics:

No (limit test)

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 1

Clinical signs:

other: Signs of toxicity related to dose levels: Clinical signs prior to death of the single female that died on day 2: piloerection and hunched posture. Surviving animals: no clinical signs or altered behaviour observed.

Gross pathology:

Congestion and increased size of the spleen in the single female rats which died during the study.
No changes at the end of the observation period in the other animals.

Other findings:

Signs of toxicity (local):
Local irritation was observed on all animals at the application site up to days 3-11 of the study.

Interpretation of results:

not classified

Remarks:

Migrated information EU CLP criteria Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 value of GM102E in Sprague-Dawley rats was established to be > 2000 mg/kg. One female rat died and local irritation was observed on all animals at the application site up to days 3-11 of the study.

Executive summary:

The acute dermal toxicity of the test item GM102E was investigated in a limit test performed on Sprague Dawley rats. 

The study was performed according to EU method B.3 and in compliance with GLP.

The test item was administered once on 5 males and 5 females using patch applied on the dorsal surface. The test item was tested at the concentration of 2000 mg/kg. No washing was performed and residual substance was wiped off after 24-hour exposure period.

The animals were then observed during 14 days. Clinical signs were observed at 30 min, 2, 4, 6 hours post dosing, then twice daily while weight was measured twice before dosing (at randomisation and on day 1 before treatment), then on day 8 and 15.

One female rat died during the study (day 2). Piloerection and hunched posture were observed before death and congestion and increased size of the spleen were the only findings at autopsy. No general clinical signs were seen in the surviving animals, but they showed erythema, edema, and crusts at the application site starting from days 2-3 and lasting up to days 3-11 of the study. The body weight gain appeared normal. No changes were found at the gross pathology examination performed at the end of the observation period in any rat.

Mortality was confined to only one animal and only local irritation was observed at the application site on the other rats. Thus the LD50 was considered to be > 2000 mg/kg b.w.

Based on these results and according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP), GM102E should not be classified for dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

Only one reliable study available.

Additional information

Oral route:

Two studies are available to assess the acute oral toxicity of GM102E. The first study (RBM, 1994) was performed according to OECD guideline 401 and in compliance with GLP. The study was considered as reliable without restriction (reliability 1) according to the Klimisch scoring system. A LD50 (male/female) of 123 mg/kg bw was obtained on rats and the substance has to be considered as Toxic if swallowed according to the Regulation No 1272/2008. This result is supported by a reliability 2 study (FARMOPLANT, 1983) performed according to a scientific protocol on rats. In this study, a DL50 (male/female) of 160 mg/kg bw was obtained leading to the same conclusion on classification.

Inhalation route:

Only one study of reliability 1 according to Klimisch scoring method is available for the assessment of the acute inhalation toxicity of GM102E. The study was performed according to the OECD guideline 403 without any deviations and in compliance with GLP. GM102E was administered as an aerosol by inhalation (nose only) for 4 hours to two groups of five male and five female Wistar rats at a concentration of 0.4 and 0.06 mg/L, respectively. The inhalatory LC50, 4hvalue of GM102E in Wistar rats was established to be within the range of 0.05 – 0.5 mg/L. Thus GM102E has to be considered as Toxic if inhaled according to the Regulation No 1272/2008.

Dermal route:

Only one study of reliability 1 according to Klimisch scoring method is available for the assessment of the acute dermal toxicity of GM102E. The study was performed according to the EU method B.3 without any deviations and in compliance with GLP. In this study, five males and five females were exposed to GM102E at the concentration of 2000 mg/kg bw. One female died during the study, no general clinical signs were seen in the surviving animals but they showed erythema, edema and crusts at the application site from days 2 -3 to days 3 -11 of the study. The LD50 was considered to be > 2000 mg/kg bw and the GM102E should not classified for acute dermal toxicity according to the Regulation No 1272/2008.

Justification for selection of acute toxicity – oral endpoint
The study was performed according to an OECD guideline and in compliance with GLP. No deviations were observed during the study.

Justification for selection of acute toxicity – inhalation endpoint
The study was performed according to an OECD guideline and in compliance with GLP. No deviations were observed during the study.

Justification for selection of acute toxicity – dermal endpoint
The study was performed according to the standardised EU method B.3 following EC Dir 84/449 and in compliance with GLP. No deviations were observed during the study.

Justification for classification or non-classification

GM102E is classified as toxic if swallowed according to the CLP Regulation (EC) No. 1272/2008.

GM102E is classified as fatal if inhaled (Acute Tox. Category 2) for acute inhalation toxicity according to Regulation (EC) 1272/2008 (CLP).

The test material appears to have no acute dermal toxicity in studies with rat. Therefore, GM102E is not classified for acute toxicity according to Regulation (EC) 1272/2008 (CLP).