Phosphonium, triphenyl(3,7,11-trimethyl-2,4,6,10-dodecatetraenyl)-

Endpoint summary

Description of key information

In an OECD 423 acute oral toxicity study in rats, the LD 50 was found to be greater than 200 mg/kg bw and less or equal to 2000 mg/kg bw.

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 22, 1996

GLP compliance:

yes

Remarks:

Study director

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Manufacturing date: August 1998

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, exclusion of oxygen (under nitrogen)
- Solubility and stability of the test substance in the solvent: proven good solubility

FORM AS APPLIED IN THE TEST: solution

Species:

rat

Strain:

Wistar

Remarks:

chbb: thorn

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Boehringer Ingelheim Pharma KG
- Age at study initiation: young
- Weight at study initiation: 177-180 g (male), 175-181 g (female)
- Fasting period before study: animals were given no feed at least 16 hours before administration, but water was available ad libitum
- Housing: single in stainless steel wire mesh cages, type DK-III (Becker & Co., Castrop-Rauxel, FRG)
- Diet: Kliba-Labordiaet, Provimi Kliba SA, Kaiseraugst, Switzerland, ad libitum
- Water: tap water ad libitum
- Acclimation period: at least one week

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

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

bidest

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

200 mg/kg (2 kg/ 100 mL), 2000 mg/kg (20 kg/ 100 mL) only tested in three separate females

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days for the 200 mg/kg dose group; 1 day for the 2000 mg/kg dose group
- Frequency of weighing: shortly before application (day 0), weekly thereafter and at the end of the study (before fasting period)
- Clinical signs including body weight recorded several times on the day of administration
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - <= 2 000 mg/kg bw

Mortality:

2000 mg/kg dose group: all animals died 1 day after application
200 mg/kg dose group: delayed mortality observed in 1 male and 1 female rat, which died 6 and 11 days after application, respectively

Clinical signs:

other: 2000 mg/kg dose group: impaired general state and dyspnoea 200 mg/kg dose group: impaired and poor general state, dyspnoea, gasping, apathy, staggering, spastic gait, diarrhea, exsiccosis, extended abdomen, red discoloured urine, compulsary gnawing and re

Gross pathology:

- dilation of the stomach and of the small and large intestine with gaseous or watery contents and erythema of the small intestine

Table 1: Symptoms of the male animals (cageside observations)

Dose (mg/kg) 200	numer animals (n) with symptoms	time period showing symptoms
Impaired general state	3/3	h1 d1-d2
Poor general state	3/3	d1-d2
Dyspnoea	3/3	h1-h4 d5-d9
Gasping	1/3	h1-d2
Apathy	3/3	h1-h4
Staggering	1/3	h1-h4
Piloerection	3/3	h1-d9
Diarrhea	1/3	h3-h4
Exsiccosis	1/3	d5-d9
Weight reduction	1/3	d7-d9
Extended abdomen	1/3	d9
Red clammy snout	1/3	d1

h: hour, d: day

Table 2: Symptoms of the female animals (cageside observations)

Dose (mg/kg)	200		2000
	numer animals (n) with symptoms	time period showing symptoms	numer animals (n) with symptoms	time period showing symptoms
Impaired general state	1/3	d6-d9	3/3	h2-h4
Poor general state	3/3	h1-h5 d2-d3
Dyspnoea	3/3	d2-d3 d2-d9	3/3	h2-h4
Apathy	3/3	h1-h5 d2-d3
Staggering	3/3	h5 d2-d3
Spastic gait	1/3	d3
Piloerection	3/3	h5 d2-d9
Smeared fur	2/3	d2-d3
Diarrhea	3/3	h5
Exsiccosis	2/3	d2-d3
Discoloured urine red	1/3	d3
compulsory gnawing	3/3	h1-h2
Red clammy snout	2/3	d2-d3

h: hour, d: day

Table 3: Mortality of the female animais (cumulative)

Dose	(mg/kg):	200
No.of	animals:	3
after:
h0		0
d11		1
d14		1

Table 4: Mortality of the female animais (cumulative)

Dose	(mg/kg):	200	2000
No.of	animals:	3	3
after:
d1		0	3
d6		1
d14		1

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the conditions of this study the median lethal dose of the test substance after oral application was found to be greater than 200 mg/kg and less or equal to 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

200 mg/kg bw

Additional information

Oral route

The study was performed to assess the acute toxicity following oral administration of the test substance, applied as a solution in aqua bidest., in Wistar rats. The study procedure was based on the OECD 423.

To a group of six fasted animals <three males and three females) a single oral dose of the test material preparation in aqua bidest. at a dose level of 200 mg/kg body weight was given. Another group of three female animals was treated in the same way with a dose of 2000 mg/kg body weight.

Signs of toxicity noted in the 200 mg/kg dose group comprised impaired and poor general state, dyspnoea, gasping, apathy, staggering, spastic gait, diarrhea, exsiccosis, extended abdomen, red discoloured urine, compulsary gnawing and red clammy snout. The surviving animals appeared normal within 10 days after application. The animals of the 2000 mg/kg dose group showed impaired general state and dyspnoea.

The expected body weight gain was generally observed in the course of the study, with the exception of 1 male and 1 female rat of the 200 mg/kg dose group, which showed weight reduction uip to death on day 6 or 11.

All animais of the 2000 mg/kg dose group were found dead 1 day after application. A delayed mortality was observed in 1 male and 1 female rat of the 200 mg/kg dose group, which died 6 respectively 11 days after application. Necropsy findings of the animals that died comprised dilation of the stomach and of the small and large intestine with gaseous or watery contents and erythema of the small intestine.

No abnormalities were noted at necropsy of animals sacrificed at the end of the study.

Under the conditions of this study the median lethal dose of the test substance after oral application was found to be greater than 200 mg/kg and less or equal to 2000 mg/kg body weight.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008, as amended for the thirteenth time in Regulation (EU) No 2018/1480. As a result the substance is classified for acute toxicity, Cat. 3, H301: Toxic if swallowed under Regulation (EC) No. 1272/2008.