Phosphonium, [5-(4-hydroxy-2,6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-3-methyl-2,4-pentadien-1-yl]triphenyl-, bromide (1:1)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to EEC Directive 92/69, B.1 and "Acute Toxic Class Method (ATC Method)" by E.Schlede et all., Arch. Toxicol. 66: 455-470 (1992). Test conducted under GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Acute toxic class method (ATC Method) by E. Schlede, U. Mischke, R. Roll, D. Kayser: A national validation study of the acute-toxic-class method - an alternative to the LD50 test. Arch. Toxicol. 66: 455-470 (1992).

Principles of method if other than guideline:

Method: other: Directive 92/69/EEC, B.1

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[(5-(4-hydroxy-2,6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-3-methyl-2,4-pentadienyl](triphenyl)phosphonium bromide

EC Number:

617-589-0

Cas Number:

84592-32-5

Molecular formula:

C33 H36 O2 P .Br

IUPAC Name:

[(5-(4-hydroxy-2,6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-3-methyl-2,4-pentadienyl](triphenyl)phosphonium bromide

Details on test material:

- name of test substance: ASTA-C15-Salz Krist.
- chemical name: [5-(4-Hydroxy-2,6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-3-methyl-2,4-pentadienyl]triphenylphosphoniumbromid
- substance number: 96/337
- batch number: 95/49-4B/Trommel 2
- CAS number: 84592-32-5
- degree of purity/content: 98 G/100 G (HPLC)
- date of manufacturing: 08-Nov-1995
- physical state/appearance: solid, crystalline, ochre
- storage conditions: room temperature, exclusion of light, moisture and oxygen (storage under nitrogen).

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, FRG
- Age at study initiation: young adult animals
- Weight at study initiation: 150 - 300 g (+/- 20% of mean weight)
- Fasting period before study: at least 16 hours
- Housing: single housing in stainless steel wire mesh cages; sawdust in the waste trays.
- Diet (e.g. ad libitum): Kliba-Labordiaet, Klingentalmuehle AG, Kaiseraugst, Switzerland, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 h/12 h

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 4 g/100 mL (for 200 mg/kg bw level) and 40 g/100 mL (for 2,000 mg/kg bw level).
- Amount of vehicle (if gavage): max. 5 mL

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on physical and chemical characteristics of the test substance and the composition, no pronounced acute oral toxicity was expected. Therefore, o starting dose of 2,000 mg/kg bw was selected.

Doses:

200 and 2,000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Signs: several times on the day of administration and at least once each workday thereafter. Weighing before and on ce a week after application.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, ptathology

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

200 - 2 000 mg/kg bw

Mortality:

Males
No mortality at the 200 mg/kg bw dose level.
1/3 males was found dead after 5 h at the 2,000 mg/kg bw dose level.

Females
No mortality at the 200 mg/kg bw dose level.
3/3 males were found dead after 2 h at the 2,000 mg/kg bw dose level.

Gross pathology:

Necropsy findings

Animals that died: 2,000 mg/kg bw
- Agonal congestive hyperemia: 3 females
- Stomach: contents watery (1 male); deposit of test substance, slight, yellow (2 females); deposit of test substance, moderate, yellow (1 female).
- Glandular stomach: deposition, yellow, moderate (1 male); erosion/ulcer, few. diameter up to 1 mm, black (1 female).
- small intestine: discoloration of contents, yellow (1 male)

Sacrificed animals
- organ without particular findings: 2,000 mg/kg bw (2 males); 200 mg/kg bw (3 females, 3 males).

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study the median lethal dose of ASTA-C15- Salz Krist. after oral application was found to be greater than 200 mg/kg bw and less or equal to 2,000 mg/kg bw. Thus, the test substance needs to be classified acute tox. Cat. 4 and R22, according to Regulation (EC) No. 1272/2008.