Phosphorothioic triamide, N-propyl-

Endpoint summary

Description of key information

LD50(oral) > 2000 mg/kg (BASF, 2008)
LD50(dermal) > 2000 mg/kg (BASF, 2010)

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:

April - July 2008

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:

December 17, 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(from the competent authority) Baden-Württemberg Umweltministerium

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: 8712 / 056
- Purity: > 95 %
- Physical state / color: solid / white

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: < - 18 °C
- Solubility and stability of the test substance in the vehicle: Good homogeneity in olive oil Ph. Eur / DAB. The stability of the test substance in the vehicle was determined indirectly by the concentration control analysis by the sponsor. For this purpose, the samples taken were stored at room temperature over the maximum duration of the administration period and were subsequently deep-frozen and sent to the sponsor for analysis.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: For better handling the test substance was ground with a mortar and a pistel. The test substance preparation was produced for each administration group shortly before administration by stirring with a high speed homogenizer (Ultra-Turrax) and a magnetic stirrer. The homogeneity of the test substance preparation during application was provided by stirring with a magnetic stirrer.

FORM OF ADMINISTRATION
Emulsion

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 10 - 11 weeks
- Weight at study initiation: 178 g (group 1) and 187 g (group 2) ± 20 %, respectively
- Fasting period before study: feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum
- Housing: The animals were housed in fully air-conditioned rooms.
- Diet (e.g. ad libitum): VRF1 (P), SDS Special Diets Services, 67122 Altrip, Germany
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 20 - 80 %
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 g/100 mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: good homogeneity in olive oil Ph. Eur / DAB

CLASS METHOD
- Rationale for the selection of the starting dose: By the request of the sponsor a starting dose of 2000 mg/kg body weight has been chosen in the first step with 3 female animals. As none of these animals died, 2000 mg/kg body weight was administered to an additional group of 3 female animals in a second step. Because no mortality occured the study was terminated.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 female animals

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation
- recording of signs and symptoms several times on the day of administration, at least once each work day for the individual animals
- a check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays
- necropsy with gross-pathology examination on the last day of the observation period after killing by CO2-inhalation in a chamber with increasing concentrations over time
- no histological examinations were performed
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,mortality, necropsy, gross-pathology examination

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality observed

Mortality:

No mortality occured.

Clinical signs:

other: Clinical observation revealed impaired general state, dyspnea, reduced feces, staggering, salivation, exsiccosis and piloerection. Findings were observed from hour 0 through up to study day 8 after administration.

Gross pathology:

No macroscopic abnormalities were noted in the animals examined on the last day of observation.

Interpretation of results:

GHS criteria not met

Remarks:

no mortality observed

Conclusions:

Under the conditions of this study the median lethal dose of the test substance after oral administration was found to be greater than 2000 mg/kg body weight in rats.

Executive summary:

The study was performed to assess the acute toxicity following oral administration of the test substance in Wistar rats.

Single doses of 2000 mg/kg body weight of the test material preparations in olive oil Ph. Eur. / DAB were given to 2 test groups of three fasted female animals each, (2000 mg/kg in 6 females) by gavage in a sequential manner.

No mortality occured.

Clinical observation revealed impaired general state, dyspnea, reduced feces, staggering, salivation, exsiccosis and piloerection. Findings were observed from hour 0 through up to study day 8 after administration.

The mean body weights of the administration groups increased normally throughout the study period.

No macroscopic pathologic abnormalities were noted in the animals on the last day of observation.

Under the conditions of this study the median lethal dose of the test substance after oral administration was found to be greater than 2000 mg/kg body weight in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no 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:

April - May 2010

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:

no

GLP compliance:

yes

Remarks:

(from the competent authority) Umweltministerium Baden-Württemberg

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Crl:Wl (Han) SPF

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks.
- Weight at study initiation: 239 - 283 g (males); 209 - 231 g (females)
- Housing: single housing in Makrolon cages, type III
- Diet (e.g. ad libitum): VRF1 (P); SOS Special Diets Services, 67122 Altrip, Germany)
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

olive oil

Remarks:

Ph. Eur.

Details on dermal exposure:

TEST SITE
- Area of exposure: 40 cm2
- % coverage: 10%
- Type of wrap if used: semi occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2860 mg/kg b.w. (because the test-substance preparaton in a higher concentration was a paste, the preparation was not applicable in mL. The dosing for each animal has been provided in g by using a scale)
- Concentration (if solution): 70 g/100 mL (paste)
- Paste formed: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg b.w.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no macroscopic pathologic abnormalities noted

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no macroscopic pathologic abnormalities noted

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no macroscopic pathologic abnormalities noted

Mortality:

No mortality occurred.

Clinical signs:

other: No systemic clinical signs were observed during clinical examination. No local effects were observed.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose (LD50) of LIMUS-Sambaydestillation after dermal application was found to be greater than 2000 mg/kg bw in male and female rats. Based on the results presented in this study, the test substances has not to be classified according to Directive 67/548/EEC and and GHS (UN) criteria.

Executive summary:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the test substance (as suspension in olive oil Ph. Eur.) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi occlusive dressing for 24 hours. The application area comprised at least 10 % of the total body surface area. The animals were observed for 14 days.

No mortality occured. Accordingly, the acute dermal median lethal dose (LD50) was determined to be

LD50, dermal, rat > 2000 mg/kg bw

No signs of systemic toxicity or skin effects were observed in the animals.

The mean body weight of the animals increased within the normal range throughout the study period.

No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity:

There is no acute oral toxicity study for NPPT available but the following data is suitable for a read across:

The study was performed to assess the acute toxicity following oral administration of the test substance in Wistar rats.

Single doses of 2000 mg/kg body weight of the test material preparations in olive oil Ph. Eur. / DAB were given to 2 test groups of three fasted female animals each, (2000 mg/kg in 6 females) by gavage in a sequential manner.

No mortality occured.

Clinical observation revealed impaired general state, dyspnea, reduced feces, staggering, salivation, exsiccosis and piloerection. Findings were observed from hour 0 through up to study day 8 after administration.

The mean body weights of the administration groups increased normally throughout the study period.

No macroscopic pathologic abnormalities were noted in the animals on the last day of observation.

Under the conditions of this study the median lethal dose of the test substance after oral administration was found to be greater than 2000 mg/kg body weight in rats.

Acute dermal toxicity:

There is no acute dermal toxicity study for NPPT available but the following data is suitable for a read across:

In an acute dermal toxicity study (Limit Test) according to OECD 402 guideline and GLP (BASF, 2010), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of LIMUS Sambaydestillation (as suspension in olive oil Ph.Eur.) to the clipped skin (dorsal and dorso-Iateral parts of the trunk) and covered by semi occlusive dressing for 24 hours.

The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days.

No mortality occurred. Accordingly, the acute dermal median lethal dose (LD50) in rats was determined to be > 2000 mg/kg bw.

No signs of systemic toxicity or skin effects were observed in the animals.

The mean body weight of the animals increased within the normal range throughout the study period.

No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Read Across justification:

LIMUS-Sambaydestillation is a reaction mass of phosphorothioic triamide, N-butyl- (NBPT) and phosphorothioic triamide, N-propyl- (NPPT), the subject of this registration. The relation of NBPT and NPPT in the reaction mass is ca. 3:1 and the overall total content of NBPT and NPPT in the reaction mass is up to 85 %. Thus, as the reaction mass contains a certain amount of NPPT (up to ca. 21 %) and based on the structural similarities between NBPT and NPPT (NPPT is one CH2 -group shorter) the reaction mass is suitable for a read across and thus for filling the data gaps of NPPT.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classificat ion purposes under Regulation 1272/2008. No mortality occured at the limit dose of 2000 mg/kg bw. As a result, the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EC) No. 2017/776.