Propanoic acid, 3-[[bis(2-methylpropoxy)phosphinothioyl]thio]-2-methyl-

Endpoint summary

Description of key information

The substance does not cause mortality upon single dermal application of 2000 mg/kg bw as tested in a GLP-compliant study following OECD testing guideline 402 (1987). Upon single oral application of 2000 mg/kg bw as tested in a GLP-compliant study following OECD testing guideline 423 (1996) one female was found dead 3 hours after treatment. No clinical signs or mortality were noted during the observation period in all other animals.

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:

1999

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:

(March 1996)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (17 - 23°C) away from direct sunlight
- Stability under test conditions: substance was found to be homogeneously distributed in PEG 300 and stable for at least 2 hours at room temperature

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain as stated in report: HanIbm: WIST (SPF)
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, CH-4414 Füllingsdorf / Switzerland
- Age at study initiation: Females 10 weeks, males 8 weeks
- Bodyweight at study initiation: Female: 175 - 187 g, males 207 - 222 g
- Fasting period before study: 16 hours
- Housing: Groups of 3 in Makrolon type-4 cages
- Diet (e.g. ad libitum): Pelleted Standard Kliba 3433, rat maintenance diet, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimatisation: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 3 °C
- Humidity (%): 40 - 70%
- Air changes (per hr):10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on oral exposure:

The test article was suspended in vehicle at a concentration of 0.2 g/mL and administered at a volume of 10 mL/kg BW by oral gavage. Test article was mixed with vehicle using a magnetic stirrer as homogenizer. Homogeneity of test article in the vehicle was maintained during treatment. The preparation was made shortly before each using.

Doses:

2000 mg/kg BW

No. of animals per sex per dose:

3 males and 3 females were dosed as described above.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations for mortality and clinical symptoms: 4-times on first day, afterwards once daily
- Frequency of weighing: On first day, day 8 and day 15
- Necropsy of survivors performed: yes, all animals were sacrificed and subjected to gross pathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: One of three females was found dead 3 hours after treatment. None of the treated males died.

Mortality:

One of three females was found dead 3 hours after treatment. None of the treated males died.

Clinical signs:

other: Ruffled fur, ventral position and convulsions were observed in the one female before it died. A relation to the application method can not be excluded. No clinical signs were noted during the observation period in all other animals.

Gross pathology:

No macroscopic findings were observed at necropsy.

Body weight of male and female rats following single oral administration of 2000 mg/kg bw of test article

Body weight in grams:
Sex	Animal No.	Day of Treatment	Day 8	Day 15
Female	1	183.4	*
	2	175.0	192.9	203.4
	3	186.7	199.8	207.3
Male	4	206.9	258.5	291.1
	5	222.3	278.3	316.9
	6	215.8	263.5	291.8

* animal died

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant

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:

1999

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:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (17 - 23°C) away from direct sunlight

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain as stated in the report: HanIbm: WIST (SPF)
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, CH-4414 Füllingsdorf / Switzerland
- Age at study initiation: males 9 weeks, females 12 weeks
- Weight at study initiation: males 233 - 253 g, females 203 - 224 g
- Housing:During acclimatisation 5 in Makrolon type-4 cages, during treatment and observation individually in Makrolon type-3 cages
- Diet (e.g. ad libitum): Pelleted standard Kliba 3433, rat maintenance diet , ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 40 - 70%
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back of animals
- % coverage: 10 % of total body surface
- Type of wrap if used: semi-occlusive dressing fixed with an elastic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing: Skin was flushed with lukewarm tap water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant concentration used: yes, 100 % of pure compound

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males, 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations for mortality and clinical symptoms: 4-times on first day, afterwards once daily
- Frequency of weighing: On first day, day 8 and day 15
- Necropsy of survivors performed: yes, all animals were sacrified and subjected to gross pathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: None of the treated animals died. No clinical signs were observed.

Mortality:

No animal died.

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

No macroscopic findings were observed at necropsy.

 Body weight of male and female rats after single dermal treatment with 2000 mg/kg bw of test article

Body weight in grams:
Sex	Animal No.	Day of treatment	Day 8	Day 15
male	1	252.8	276.6	310.9
	2	246.8	260.8	284.6
	3	232.8	251.5	269.3
	4	253.4	270.9	298.4
	5	234.7	246.7	266.4
female	6	210.3	218.3	223.9
	7	202.7	203.1	212.3
	8	211.5	215.7	227.7
	9	223.7	223.5	234.7
	10	205.7	208.3	214.7

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and guideline compliant

Additional information

Acute oral toxicity

Three male and female rats were given 2000 mg/kg bw test article by oral gavage. There were no signs of toxicity for five rats until they were sacrificed 14 days after treatment. One female was found dead 3 hours after treatment. All other animals survived until scheduled necropsy. Before the female was found dead ruffled fur, ventral position, and convulsions were observed. The cause of death is unknown. A relation to the application method (gavage) cannot be excluded. No clinical signs were noted during the observation period in all other animals.

In a supporting study performed two years earlier, rats were treated by gavage with 2000 mg/kg per body weight and no mortalities occurred; the LD50 was established at > 2000 mg/kg for both males and females.

Acute dermal toxicity

A group of five male and five female Hanlbm: WIST (SPF) rats was treated at 2000 mg/kg bw by dermal application. The test article was applied undiluted. The animals were examined for clinical signs four times during day 1 and once daily during days 2-15. Mortality was recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. No clinical signs were observed during the observation period. The body weight of the animals was within the range commonly recorded for this strain and age.

Acute inhalation toxicity

Experimental data on inhalatory toxicity is not available.

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 classification purposes under Regulation 1272/2008. As a result, the substance is not considered to be classified for acute oral and dermal toxicity under Regulation (EC) No. 1272/2008.