O,O,O-tris(2(or 4)-C9-10-isoalkylphenyl) phosphorothioate

Endpoint summary

Description of key information

The substance is practically non-toxic in the rat after oral and dermal exposure with LD 50s higher than 2000 mg/kg bw, respectively. The tests were performed pursuant OECD Guideline 401 (Acute oral Toxicity) and 402 (Acute Dermal Toxicity), respectively. Experimental data on acute inhalation toxicity is not available.

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:

January 16, 1989 - February 2, 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

(1987)

Deviations:

no

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

Species:

rat

Strain:

other: Tif: RAI f (SPF)/albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Ltd. Animal production, 4332 Stein/Switzerland
- Age at study initiation: 7-8 wks
- Weight at study initiation: weight variations do not exceed ± 20 per cent of the mean weight (range 166 -212 g)
- Fasting period before study: yes (overnight)
- Housing: 5/cage in Macrolon cages type 4, with standardized soft wood bedding (Societe Parisienne des Sciures, Pantin)
- Diet: ad libitum; Rat chow (NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland)
- Water: ad libitum
- Acclimation period: at least 5 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Details on oral exposure:

VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: the test substance is insoluble in water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

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: daily
- Frequency of weighing: at start and on days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

From the body weights, the group means and their standard deviations were calculated.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

No mortality occurred up until termination (day 14). Clinical signs of toxicity were non specific (piloerection, hunched posture and dyspnoea)

Mortality:

none

Clinical signs:

other: Unspecific signs of poisoning: piloerection, hunched posture and dyspnoea. The animals recovered within 6 days.

Gross pathology:

At necropsy, no deviations from normal morphology were found.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of the test article in rats was established to exceed 2000 mg/kg body weight.

Executive summary:

In an acute oral toxicity study according to OECD guideline 401, five male and five female rats were dosed once with the test article in peanut oil by gastric intubation at a dose level of 2000 mg/kg body weight and observed for 14 days. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. No mortalities were recorded. Piloerection, hunched posture and dyspnoea were observed in all animals. The animals recovered within 6 days. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of the test article in rats was established to be greater than 2000 mg/kg body weight.

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 study.

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:

January 17, 1989 - January 31, 1989

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

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

Species:

rat

Strain:

other: Tif: RAI f (SPF)/albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Ltd. animal production, 4332 Stein/Switzerland
- Age at study initiation: 7-8 wks
- Weight at study initiation: weight variations do not exceed ±20 per cent of the mean weight range (217 - 255 g)
- Housing: individually housed in Macrolon cages type 3, with standardized soft wood bedding (Societe Parisienne des Sciures, Pantin)
- Diet: ad libitum; Rat chow (NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland)
- Water: ad libitum
- Acclimatization period: at least 5 days before application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hour): approx. 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: at least 10% of body surface (back)
- % coverage: no data
- Type of wrap if used: adhesive elastic bandage

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mL/kg bw
- Concentration (if solution): undiluted
- 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:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: at start and on days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

From the body weights, the group means and their standard deviations were calculated.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

Clinical symptoms: piloerection, abnormal body positions and dyspnea (recovered within 6 days)

Mortality:

no mortalities

Clinical signs:

other: Unspecific signs of poisoning: piloerection, abnormal body positions and dyspnea. The animals recovered within 6 days in all animals.

Gross pathology:

At necropsy, no deviations from normal morphology were found.

Other findings:

no signs of local toxicity

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 value of the test article in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

The acute dermal toxicity of the test substance was assessed in a toxicity study following OECD guideline 402 and in compliance with GLP. The test article was administered to five Tif: RAI f (SPF) rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. No mortality occurred. Unspecific signs of poisoning: piloerection, abnormal body positions and dyspnea. The animals recovered within 6 days in all animals. The mean body weight gain during the observation period was within the expected range. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of the test substance in rats was established to exceed 2000 mg/kg body weight.

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 study.

Additional information

Acute Oral Toxicity

In the key study performed according to the protocols of OECD 401 (Acute Toxicity (Oral)), groups of fasted (overnight), 7- 8 weeks old (Tif: RAI f (SPF)) albino rats (5/sex/dose) were given a single oral dose of the test article (96.2 % pure) in peanut oil at the limit dose 2000 mg/kg bw and were observed for 14 days. No mortality occurred during observation period (LD50 > 2000 mg/kg bw). There were no treatment related clinical signs of toxicity. Clinical signs of toxicity were limited to nonspecific signs of poisoning namely: piloerection, hunched posture and dyspnoea. The animals recovered within 6 days. There were no treatment related necropsy findings or changes in body weight. In a supporting exploratory study similar results were reported.

 

Acute Dermal Toxicity

In the key study performed according to the protocols of OECD 402 (Acute Toxicity (Dermal)), groups of fasted (overnight), 7- 8 weeks old (Tif: RAI f (SPF)) albino rats (5/sex/dose) were given a single dermal dose of the test article (96.2 % pure) at the limit dose 2000 mg/kg bw. The exposure period was 24 h and the observation period 14 days. No mortality occurred during observation period (LD50 > 2000 mg/kg bw). There were no treatment related clinical signs of toxicity. Clinical signs of toxicity were limited to nonspecific signs of poisoning namely: piloerection, abnormal body positions and dyspnea. The animals recovered within 6 days. There were no treatment related necropsy findings or changes in body weight.

 

Acute Inhalation Toxicity

No data 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 the purpose of classification under Regulation (EC) No 1272/2008. Based on the data, classification for acute toxicity is not warranted under Regulation (EC) No 1272/2008, as amended for the eighth time in Regulation (EU) No 2016/218.