Bis(2,4,4-trimethylpentyl)phosphinic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From November 4th,1981 to April 22nd, 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

no certificate of analysis and no data on the animal environmental conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

: no certificate of analysis, no data on the animal environmental conditions (temperature, humidity, air change)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2,4,4-trimethylpentyl)phosphinic acid

EC Number:

280-445-7

EC Name:

Bis(2,4,4-trimethylpentyl)phosphinic acid

Cas Number:

83411-71-6

Molecular formula:

C16H35O2P

IUPAC Name:

bis(2,4,4-trimethylpentyl)phosphinic acid

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Portage, Michigan and Kingston, NY, USA
- Age at study initiation: no data
- Weight at study initiation: from 193.82 to 229.44 g
- Fasting period before study: yes, 24h prior to oral administration of test substance
- Housing: individually housed in wire-bottomed cages suspended above the droppings.
- Diet (e.g. ad libitum): Purina Certified Rodent Chow 5002, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: yes for 6 to 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: To: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 6.63 ml/kg

Doses:

range finding study: 2.5; 3.5; 6.5; 7.5 g/kg bw
main test: 2.5; 3.5; 4.0; 5.0; 6.5 g/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 and weighing: observation twice daily, weighing on days -1; 0; 1; 2; 3; 6; 10 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy of visceral and thoracic cavity

Statistics:

The Litchfield and Wilcoxon method was used to calculate the LD50

Results and discussion

Preliminary study:

at 2.5 g/kg bw: 2/4 anaimals died on day 1
at 3.5 g/kg bw: 1/4 animals died on day 1
at 6.5 g/kg bw: 4/4 animals died on day 1
at 7.5 g/kg bw: 3/4 animals died on days 1, 2 and 3

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

5 719 mg/kg bw

Based on:

test mat.

95% CL:

>= 5 037 - <= 6 494

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

4 500 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 947 - <= 6 870

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 444 mg/kg bw

Based on:

test mat.

95% CL:

>= 3 070 - <= 9 653

Remarks on result:

other: This does not include females died at 4.0 g/kg due to the dosing technique

Mortality:

2.5 g/kg bw: 2/10 (day 3 and 6)
3.0 g/kg bw: 0/10
4.0 g/kg bw: 5/10 (4 females died on day 0. It appeared to be related to dosing technique. One male died on day 1)
5.0 g/kg bw: 4/10 (day 1, 2 and 6)
6.5 g/kg bw: 8/10 (day 1 and 2)

Clinical signs:

other: Signs of systemic toxicity were observed 30 min after dosing at all dose levels. Reactions ranged from lethargy, bodies cool to touch, red material round mouth/nose, loose feces and fecal stains to ataxia and inactivity. The severity and incidence of reac

Gross pathology:

Positive gross pathologic findings were observed at all dose levels : gastrointestinal hemorrhage or appeared reddened, thickened area of stomach, intestines mucoid, intestine empty (at 6.5 g/kg bw dose level only).

Any other information on results incl. tables

Mortality after an oral administration of the substance

 

Dose (mg/kg)	Mortality (# dead/total)			Time range of death
	Male	Female	Combined
2500	0/5	2/5	2/10	Day 3 and 6
3500	0/5	0/5	0/10	-
4000	0/5	5/5	5/10	Day 0 (4 females died due to dosing technique), Day 1 (1 female)
5000	1/5	3/5	4/10	Day 2 (1 female), Day 2 (1 male and 1 female), Day 10 (1 female)
6000	4/5	4/5	8/10	Day 1 (4 males and 3 females), Day 2 (1 female)

Applicant's summary and conclusion

Interpretation of results:

other: not classified as harmful or toxic according to the CLP Regulation (EC) No.1272/2008

Conclusions:

LD50 (rat, male and female) = 5444 mg/kg bw

Executive summary:

In an acute oral toxicity study, performed similarly to the OECD guideline No. 401, and in compliance with the GLP, groups of (SD) male and female rats (5 animals/sex/dose) were given a single oral dose (by gavage) of undiluted test substance.

The initial study was conducted with one dose level of 5000 mg/kg bw with ten rats. As 4/10 rats died, a range-finding study at doses of 2500; 3500; 6500 and 7500 mg/kg bw was performed. Death was observed at any dose levels. In the main study, the rats were administered by gavage the test substance at doses of 2500; 3500; 4000; 5000 and 6500 mg/kg bw. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days.

Death is observed at all dose levels except at 3500 mg/kg bw. Signs of systemic toxicity were observed 30 min after dosing at all dose levels. Reactions ranged from lethargy, bodies cool to touch, red material round mouth and nose, loose feces and fecal stains to ataxia and inactivity. The severity and incidence of reactions increased with dose level. Furthermore, the mean bodyweight appeared to be decreased for the found dead animals. Positive gross pathologic findings were observed at all dose levels: gastrointestinal hemorrhage or appeared reddened, thickened area of stomach, intestines mucoid, intestine empty (at 6500 mg/kg bw dose level only).

Oral LD₅₀in rats (male and female) = 5444 mg/kg bw