Reaction mass of 3-phenoxybenzyl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-en-1-yl)cyclopropanecarboxylate and 3-phenoxybenzyl (1R,3S)-2,2-dimethyl-3-(2-methylprop-1-en-1-yl)cyclopropanecarboxylate (4:1)

Endpoint summary

Description of key information

D-phenothrin was tested for acute toxicity via oral, dermal and inhalation route. No mortality or clinical signs of toxicity was observed in any of these acute toxicity studies.

Acute oral txicity:

A study according to guideline of OECD NO 423 (December 2001) was performed to assess the acute oral toxicity of d-Phenothrin in Wistar rats. d-Phenothrin in 0.5% (w/v) carboxymethl cellulose was applied to Wistar rtas as single oral gavage, using intubation cannula. The first set (set I) of three female rats was given a single dose of 2000 mg d-Phenothrin/kg body weight. No mortality was observed at this dose level; hence the second set of 3 female rats (set II) was administered with same dose. As no mortality was observed, further testing was not required. No clinical symptoms or mortalities were observed in the rats treated with 2000 mg d-Phenothrin/kg body weight. The rats sacrificed at termination did not reveal any lesion of pathological significance.

The acute oral median lethal dose LD50 (cut off value) of d-Phenothrin in Wistar rats was found to be 5000 mg/kg body weight.

Acute dermal toxicity:

A study according to guideline of OECD N° 402 (February 1987) was performed to assess the acute dermal toxicity of d-Phenothrin in Wistar rats. Two groups of rats, each comprising of 5 males and 5 females were randomly selected for the study. One group (group I) served as the control and was treated with distilled water, whereas the other group (group II) was given a limit dose of 2000 mg d-Phenothrin/kg bw by dermal application and observed for a period of 14 days. No clinical symptoms or mortality were observed in the rats from either the control or the treatment group. All the rats, at the end of the observation period, were sacrificed and subjected to gross pathological examination, not revealing any lesion of pathological significance.

The acute dermal median lethal dose (LD50) of d-Phenothrin in Wistar rats was found to be greater than 2000 mg/kg body weight.

Acute inhalation toxicity:

A study according to guideline of OECD N° 403 (May 1981) was performed to assess the acute inhalation toxicity (LC50) of d-Phenothrin in Wistar rats. Two groups of rats, each consisting of five males and five females were used for the study. Rats from Group I were exposed to air only and served as the control group, whereas rats from Group II were exposed to the maximum achievable breathing zone concentration (5.301 mg/L air) of d-Phenothrin. Rats were exposed for 4 hours followed by observation for a period of 14 days. All the rats from the control and the treatment group appeared normal throughout the experiment period. The mean body weight of rats belonging to the treatment group was comparable to that of the control group. The rats, sacrificed terminally from the control and the treatment group did not reveal any pathological abnormality.

At the maximum achievable breathing zone concentration (5.301 mg/L air) of d-Phenothrin, no mortality was observed. Hence, the acute inhalation median lethal concentration (LC50) of d-Phenothrin was concluded to be greater than 5.301 mg/L air.

In summary it can be concluded that based on studies available no acute toxicity to rodents is expected.

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:

Feb - May 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP / guideline study without deviations

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (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:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Facility, JRF
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 153-172 g
- Fasting period before study: overnight until 3 h post dosing
- Housing: 3 rats per cage, polypropylene cages, rice husk bedding
- Diet (e.g. ad libitum): rat pellet feed (Amrut brand) ad libitum
- Water (e.g. ad libitum): filtered water ad libitum
- Acclimation period: 6-8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 63-67
- Air changes (per hr): min. 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 2006-03-22 To: 2006-04-07

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

0.5% carboxymethyl cellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no mortality at 2000 mg/kg bw in a single rat

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3+3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation at 30 min, 1, 2, 3, 4, 6 h after dosing on the day of dosing, Subsequently, rats were observed twice per day. Animals were weighed weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

LD50 cut-off was determined using the flowchart provided by OECD TG 423

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

None

Body weight:

Normal weight gain was recorded.

Gross pathology:

No external or visceral abnormalities.

Interpretation of results:

GHS criteria not met

Conclusions:

No mortality or clinical signs for toxicity was oberseved in female rats treted with single doses of 2000 mg/kg bw. Thus, the test material is not classified for acute oral toxicity according to the criteria of Regulation 1272/2008.

Executive summary:

This study was performed to assess the acute oral toxicity of d-Phenothrin in Wistar rats. The method followed was as per the guidelines of OECD NO 423 (December 2001).

Wistar rats, fasted overnight, were dosed with d-Phenothrin in 0.5% (w/v) carboxymethl cellulose as single oral gavage, using intubation cannula. The food was withheld until 3 hours post dosing. The first set (set I) of three female rats was given a single dose of 2000 mg d-Phenothrin/kg body weight. No mortality was observed at this dose level; hence the second set of 3 female rats (set II) was administered with same dose of 2000 mg d-Phenothrin/kg body weight. As no mortality was observed at this dose level, further testing was not required. No clinical symptoms or mortalities were observed in the rats treated with 2000 mg d-Phenothrin/kg body weight. The rats sacrificed at termination did not reveal any lesion of pathological significance.

The acute oral median lethal dose LD50 (cut off value) of d-Phenothrin in Wistar rats was found to be 5000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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:

Feb - Oct 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP / guideline study wiith no deficiencies

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

May 12, 1981

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Facility, JRF
- Age at study initiation: 10 - 11 weeks
- Weight at study initiation: m: 230 - 264 g, f: 170 - 216 g
- Fasting period before study: no
- Housing: 5 rats per cage, polypropylene cages, rice husk bedding
- Diet (e.g. ad libitum): rat pellet feed (Amrut brand) ad libitum
- Water (e.g. ad libitum): filtered water ad libitum
- Acclimation period: min. 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23
- Humidity (%): 64 - 66
- Air changes (per hr): min. 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 2006-05-24 To: 2006-06-07

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: BIO-TOX
- Exposure chamber volume: 63.5 L
- Method of holding animals in test chamber: exposure tubes
- Source and rate of air: compressed ambient air, 12 - 15 air changes per hour, 15 L/min
- Method of conditioning air: air filter -> moisture separator -> high flow filter -> charcoal filter -> silica gel filter -> air filter with regulator
- System of generating particulates/aerosols: spray atomizer
- Method of particle size determination: seven-stage cascade impactor, gravimetric analysis
- Treatment of exhaust air: passed through NaOH solution and silica gel moisture traps
- Temperature, humidity, pressure in air chamber: 20.9 - 22.4 °C, RH: 44.3 - 48.0%, oxygen: 20.4 - 20.9%

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric
- Samples taken from breathing zone: yes
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 3.13 µm / 2.66 µm

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric

Duration of exposure:

4 h

Concentrations:

Actual concentration: 5.301 mg/L

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: hourly during exposure, twice daily for mortality/morbidity, once daily for clinical signs
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Not applicable for limit test

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.301 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality

Clinical signs:

other: No clinical signs

Body weight:

Body weights of controls and treatment groups were comparable

Gross pathology:

No external or visceral abnormalities

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

At the maximum achievable concentration (5.301 mg/L air) of d-Phenothrin, no mortality was observed. Hence, the acute inhalation median lethal concentration (LC50) of d-Phenothrin was concluded to be greater than 5.301 mg/L air. The test material is not classified for acute inhalation toxicity according to the criteria of Regulation 1272/2008.

Executive summary:

This study was performed to assess the acute inhalation toxicity (LC50) of d-Phenothrin in Wistar rats. The method followed was as per the guideline of OECD N° 403 (May 1981).

Two groups of rats, each consisting of five males and five females were used for the study. Rats from Group I were exposed to air only and served as the control group. Rats from Group II were exposed to the maximum achievable breathing zone concentration (5.301 mg/L air) of d-Phenothrin. Rats from either group were exposed for 4 hours followed by observation for a period of 14 days. All the rats from the control and the treatment group appeared normal throughout the experiment period. The mean body weight of rats belonging to the treatment group was comparable to that of the control group. The rats, sacrificed terminally from the control and the treatment group did not reveal any pathological abnormality.

At the maximum achievable breathing zone concentration (5.301 mg/L air) of d-Phenothrin, no mortality was observed. Hence, the acute inhalation median lethal concentration (LC50) of d-Phenothrin was concluded to be greater than 5.301 mg/L air.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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:

Feb - May 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP / guideline study without deficiencies

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Facility, JRF
- Age at study initiation: 10 - 11 weeks
- Weight at study initiation: m: 210 - 286 g, f: 202 - 220 g
- Fasting period before study: no
- Housing: individual, polypropylene cages, rice husk bedding
- Diet (e.g. ad libitum): rat pellet feed (Amrut brand) ad libitum
- Water (e.g. ad libitum): filtered water ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23
- Humidity (%): 63 - 67
- Air changes (per hr): min. 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 2006-03-31 To: 2006-04-14

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: not reported
- % coverage: 10
- Type of wrap if used: porous gauze dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): using cotton moistened with distilled water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: rats were observed for clinical signs and mortalities at 1, 2, 3, and 6 h post exposure. Subsequently, animals were observed twice per day for morbidity/mortality. Clinical signs were recoreded once per day. Animals were weighed prior to exposure, and on days 7 and 14 after application.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

not applicable for limit test

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality

Clinical signs:

No clinical signs

Body weight:

No effect on body weight

Gross pathology:

No external or visceral abnormalities

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of d-Phenothrin in Wistar rats was found to be greater than 2000 mg/kg body weight. Thus, the test substance is not classified for acute dermal toxicity according to the criteria of Regulation 1272/2008.

Executive summary:

This study was performed to assess the acute dermal toxicity of d-Phenothrin in Wistar rats. The method followed was as per the guidelines of OECD N° 402 (February 1987).

Two groups of rats, each comprising of 5 males and 5 females were randomly selected for the study. Approximately, 10 per cent of the body surface area was clipped 24 hours prior to the dermal application of the test substance. One group (group I) served as the control and was treated with distilled water. The other group (group II) was given a limit dose of 2000 mg d-Phenothrin/kg bw by dermal application and observed for a period of 14 days. No clinical symptoms or mortality were observed in the rats from either the control or the treatment group. All the rats, at the end of the observation period, were sacrificed and subjected to gross pathological examination. The rats sacrificed at termination belonging to the control as well as the treatment group did not reveal any lesion of pathological significance.

The acute dermal median lethal dose (LD50) of d-Phenothrin in Wistar rats was found to be greater than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

Based on results for acute toxicity studies following oral, dermal and inhalation exposure to limit concentrations, as required according to CLP (Regulation EC No 1272/2008), it can be concluded that no acute toxicty to rodents was seen and the substance d-Phenothrin is not subject to classification for acute toxicity.