Iodonium, bis[4-(1,1-dimethylethyl)phenyl]-, hexafluorophosphate(1-) (1:1)

Endpoint summary

Description of key information

Oral (OECD 423), rat: LD50 (cut-off) > 2500 mg/kg bw/day

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:

10 Jan - 16 Feb 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: RccHan: WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 173-180 g (group 1), 165-167 g (group 2), 167- 184 g (group 3)
- Fasting period before study: animals were fasted overnight prior to dosing and for approximately 3 to 4 h after dosing.
- Housing: animals were housed in groups of 3 in suspended solid-floor polypropylene cages furnished with wood flakes.
- Diet: 2014C Teklad Global Rodent diet (Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: arachis oil BP

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL (300 mg/kg bw dose group) and 200 mg/mL (2000 mg/kg bw dose group)
- Justification for choice of vehicle: arachis oil BP was used because the test substance did not dissolve/suspend in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: the dose formulations were freshly prepared within two hours before application to the animals, since the stability of the test formulation was assumed for this duration.

CLASS METHOD
- Rationale for the selection of the starting dose: in the absence of data regarding the toxicity of the test substance, 300 mg/kg bw was chosen as the starting dose.

Doses:

300 mg/kg bw (group 1), 2000 mg/kg bw (group 2 and group 3)

No. of animals per sex per dose:

3 in group 1, group 2 and group 3, respectively

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for clinical signs and mortality within the first 30 min and at approximately 1, 2 and 4 h after treatment on Day 1. During the observation period, animals were observed once daily for mortality and clinical signs. Individual body weights were recorded on Day 1 (prior to dosing) as well as 7 and 14 days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: experimental result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off according to OECD 423

Mortality:

No mortalities were observed at a dose level of 300 mg/kg bw in animals of group 1. In group 2, one animal treated at 2000 mg/kg bw was found dead on Day 9 of the 14-day observation period. Due to the occurrence of severe clinical signs, one animal of group 3, which received the test substance at at a dose level of 2000 mg/kg bw, was killed for humane reasons 4 h after dosing.

Clinical signs:

other: Signs of systemic toxicity were noted 1 to 4 h after dosing in the animal of group 2, which was treated with 2000 mg/kg bw and humanely killed 4 h after dosing. Clinical signs started with noisy respiration 1 h after dosing, followed by hunched posture, a

Gross pathology:

At the unscheduled deaths, abnormalities were noted in two animals treated at 2000 mg/kg bw. In the animal of group 1, which was found dead on Day 9 of the study, abnormally red lungs, dark liver, dark kidneys, haemorrhage and epithelial sloughing of the gastric mucosa as well as gaseous and reddened small and large intestines were observed. In the animal of group 2, which was humanely killed 4 h after dosing, white substance in the stomach and epithelial sloughing of the gastric mucosa were seen. No abnormalities were noted at necropsy of animals which were killed at the end of the 14-day observation period.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Executive summary:

The acute oral toxicity of PF-6 was investigated in a GLP-conform study according to the acute toxic class method (OECD guideline 423). In the first step, the test substance was administered to 3 female RccHan:WIST rats at a starting dose of 300 mg/kg bw in arachis oil BP by single oral gavage. In two further steps, two groups of 3 female rats each, were treated with PF-6 diluted in arachis oil BP at doses of 2000 mg/kg bw. Two unscheduled deaths occurred during the study period. One animal treated with 2000 mg/kg bw in the second step was found dead on Day 9 during the study without showing clinical signs. A further animal treated with 2000 mg/kg bw was humanely killed 4 h after dosing in the third step due to overt signs of toxicity (noisy respiration, hunched posture, ataxia, pilo-erection and lethargy). No mortality was observed in animals receiving the test substance at 300 mg/kg bw. Two animals treated in the second step and one animal treated in the third step, showed loss in body weight at 2000 mg/kg bw during the first week, but achieved the expected body weight gain during the second week of the study. All other animals showed the expected gain in body weight after treatment with the test substance. No macroscopic findings were recorded at necropsy in animals treated at 300 mg/kg bw and animals treated at 2000 mg/kg bw that survived the study period. At the unscheduled deaths, abnormalities were noted in two animals treated at 2000 mg/kg bw. In the animal found dead during the second step of treatment, abnormally red lungs, dark liver, dark kidneys, haemorrhage and epithelial sloughing of the gastric mucosa as well as gaseous and reddened small and large intestines were observed. In the animal humanely killed 4 h after dosing during the third step of treatment, white substance in the stomach and epithelial sloughing of the gastric mucosa were seen. Based on these experimental results, the LD50 of PF-6 was greater than 2000 mg/kg bw. According to the criteria of OECD guideline 423, the LD50 cut-off of PF-6 may be considered to be 2500 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral

The acute oral toxicity of PF-6 was investigated in a GLP-conform study according to the acute toxic class method (OECD guideline 423) (Bradshaw, 2012). In the first step, the test substance was administered to 3 female RccHan:WIST rats at a starting dose of 300 mg/kg bw in arachis oil BP by single oral gavage. In two further steps, two groups of 3 female rats each, were treated with PF-6 diluted in arachis oil BP at doses of 2000 mg/kg bw. Two unscheduled deaths occurred during the study period. One animal treated with 2000 mg/kg bw in the second step was found dead on Day 9 during the study without showing clinical signs. A further animal treated with 2000 mg/kg bw was humanely killed 4 h after dosing in the third step due to overt signs of toxicity (noisy respiration, hunched posture, ataxia, pilo-erection and lethargy). No mortality was observed in animals receiving the test substance at 300 mg/kg bw. Two animals treated in the second step and one animal treated in the third step, showed loss in body weight at 2000 mg/kg bw during the first week, but achieved the expected body weight gain during the second week of the study. All other animals showed the expected gain in body weight after treatment with the test substance. No macroscopic findings were recorded at necropsy in animals treated at 300 mg/kg bw and animals treated at 2000 mg/kg bw that survived the study period. At the unscheduled deaths, abnormalities were noted in two animals treated at 2000 mg/kg bw. In the animal found dead during the second step of treatment, abnormally red lungs, dark liver, dark kidneys, haemorrhage and epithelial sloughing of the gastric mucosa as well as gaseous and reddened small and large intestines were observed. In the animal humanely killed 4 h after dosing during the third step of treatment, white substance in the stomach and epithelial sloughing of the gastric mucosa were seen. Based on these experimental results, the LD50 of PF-6 was greater than 2000 mg/kg bw. According to the criteria of OECD guideline 423, the LD50 cut-off of PF-6 may be considered to be 2500 mg/kg bw.

Justification for classification or non-classification

The available data on the acute toxicity of PF-6 do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.