Triphenylphosphine oxide

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

no ophtalmological examination; no examination of sensory reactivity

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Triphenylphosphine oxide

EC Number:

212-338-8

EC Name:

Triphenylphosphine oxide

Cas Number:

791-28-6

Molecular formula:

C18H15OP

IUPAC Name:

triphenylphosphine oxide

Details on test material:

- Name of test material (as cited in study report): Triphenylphosphinoxid
- Purity: pure p.a.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SPF breeding, WIGA, Sulzfeld
- Age at study initiation (1st application): 42 d
- Weight at study initiation (1st application): males: 144 g, females 120 g
- Housing: 2 or 3 per cage
- Diet: Altromin-R, ALTROGGE, Lage/Lippe, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+-2
- Humidity (%): 55+-5
- Photoperiod (hrs dark / hrs light): 12:12

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): weekly

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days

Frequency of treatment:

continuously

Doses / concentrations

Remarks:

Doses / Concentrations:
20; 100; 500; 2500 ppm in diet (equivalent 2; 10; 50; 250 mg/kg bw; Diets (ppm) were converted to mg/kg bw by division by factor 10 [Derelanko (2000). Toxicologist's Pocket Handbook. CRC Press])
Basis:
nominal in diet

No. of animals per sex per dose:

30 (10/30 animals were used for the recovery groups)

Control animals:

yes, plain diet

Details on study design:

Post-exposure period: 42 days (recovery; 10 animals per sex per dose)

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: Body weights were recorded weekly


FOOD CONSUMPTION: Yes
-Time schedule: Food consumption was recorded daily


HAEMATOLOGY: Yes
- Time schedule for collection of blood: before the start of the study (prefeeding/acclimatisation period) , after week 4 and week 12 in all animals; after week 6 of the recovery period in all animals of the recovery group
- parameters: hemoglobin, hematocrit, erythrocyte count, mean cell volume, mean cell hemoglobin concentration of single erythrocytes, mean corpuscular hemoglobin concentration, total and differential leucocyte counts, thrombocyte count


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: before the start of the study, during week 6 and during week 13
- Animals fasted: No data
- How many animals: 10 males and 10 females
- parameters: alkaline phosphatise, glutamate pyruvate transaminase, glucose, urea, total protein, total lipid, total bilirubin, sodium, potassium, chloride, calcium, inorganic phosphate , carbon dioxide, creatinine.


URINALYSIS: Yes
- Time schedule for collection of urine after week 3, 7 and 11 in all animals; after week 5 of the recovery period in all animals of the recovery groups
- Metabolism cages used for collection of urine: yes
- parameters: pH, glucose, protein, urobilinogen, sediment

Sacrifice and pathology:

At the end of the exposure and at the end of the post exposure period, fasted animals were sacrificed and individual necropsies were performed.
Tissues examined included: heart, liver, kidney, spleen, testicles (ovaries), thyroid gland, adrenal glands, pituitary gland, brain, lung, pancreas, stomach, small intestine, large intestine, lymph nodes, skin, eyes with optic nerve, nerves, nasal and faucal mucosa, tongue, cranial bone, salivary glands, skeletal muscles, thymus, trachea, oesophagus, aorta thoracica, prostate gland, uterus, seminal vesicles, epididymis, adipose tissue, tail, left hind leg and sternum.
Following organs were weighed: heart, liver, kidneys, spleen, gonads, thyroid and adrenals (the latter two having
been fixed immediately after dissection).

Statistics:

Food uptake, body weights & organ weights: ANOVA, t-test
Clinical chemistry & hematology : Nalimov correction followed by t-test
Urinalysis: chi2-test with Yates correction

Results and discussion

Results of examinations

Details on results:

2 mg/kg bw (2 ppm):
No effect was seen.

10 mg/kg bw (100 ppm):
No effect was found concerning clinical parameters.
Hematological and clinicochemical alterations:
From the 8th week of study alkaline phosphatase activity was reduced, returning to normal in the recovery period.
Necropsy:
Reversible effects were seen for the organ weigths of liver and kidney.
Observed fine vacuolar degenerations of the liver were also reversible.

50mg/kg bw (500 ppm):
Clinical parameters:
In females feed consumption and body weight gain were reduced.
Slightly ruffled fur and hyperexcitability were described for both genders.
Hematological and clinicochemical alterations:
Increased protein contents, decreased glucose values, and increased total lipid contents in both genders.
Alkaline phosphatase activity in plasma was reduced at the end of the study, hemoglobin count was reduced in females, thrombocyte count was increased in both genders.
At the end of the recovery period, these values returned to normal.
Necropsy:
All investigated organs in males (liver, kidney, spleen, testes, adrenals), with the exception of the thyroid, showed increased absolute and relative weights.
In females, absolute liver weights were increased; the only increased relative weights were those of liver, too, and kidney.
The organ weight changes were reversible in the recovery period.
In 12/20 males and 7/20 females, degeneration in the hepatic epithelium was seen at the end of the treatment period, which could only be observed in 1/10 males and 1/10 females at the end of the recovery period.

250 mg/kg bw (2500 ppm):
Within the lethal range.
3/30 males and 4/30 females died.
Clinical parameters:
Slightly ruffled fur, nervousness, and partially distended abdomen were described, after 4 weeks of treatment increased aggression was observed.
Towards the end of the study atrophy of the muscles of the hind limbs was detected.
Food consumption and body weight gain were considerably impaired in this group.
Hematological and clinicochemical alterations:
Reduced glucose values, increased lipid values and an increased activity of alkaline phosphatase were described. Hemoglobin contents and hematocrit values were reduced, thrombocyte counts increased.
Necropsy:
The increased weights of liver and adrenals were irreversible.

Effect levels

1

Dose descriptor:

NOEL

Effect level:

ca. 2 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: equivalent to 20 ppm; no effects observed

2

Dose descriptor:

NOAEL

Effect level:

ca. 10 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: equivalent to 100 ppm; reversible effects (reduced alkaline phosphatase activity, changed liver and kidney weight, fine vascular degeneration in the liver) were considered as not adverse

3

Dose descriptor:

LOAEL

Effect level:

ca. 50 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Target system / organ toxicity

Critical effects observed:

not specified