Triethyl phosphite

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Adopted according to OECD SIDS (publicly available peer reviewed source). Original document not available.

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

SIDS Initial Assessment Report For SIAM 16 (Triethyl Phosphite), 2003 Paris.

Author:

OECD

Year:

2003

Bibliographic source:

UNEP Publications

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Version / remarks:

(adopted 1981)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Triethyl phosphite

EC Number:

204-552-5

EC Name:

Triethyl phosphite

Cas Number:

122-52-1

Molecular formula:

C6H15O3P

IUPAC Name:

triethyl phosphite

Details on test material:

Purity: 98.8%

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

(400, Lutrol)

Details on oral exposure:

VEHICLE
- Amount of vehicle: 5 mL/kg bw

Duration of treatment / exposure:

32 days

Frequency of treatment:

Once daily

Doses / concentrations

Remarks:

Doses / Concentrations:
30, 150, or 750 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

FOOD CONSUMPTION AND WATER CONSUMPTION: Yes

HAEMATOLOGY: Yes
Red blood cell count (RBC), hemoglobine (Hb), hematocrit (Hct), white blood cell count (WBC), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), Platelets, differential WBC, coagulation

CLINICAL CHEMISTRY: Yes
Alkaline phosphatase, aspartate amino transferase (ASAT), alanine amino transferase (ALAT), glucose, bilirubin, cholesterol, triglycerides, creatinine, total protein, urea, albumin, phosphate, calcium, chloride

URINALYSIS: Yes
Spec. gravity, volume, bilirubin, blood, Hb, ketones, pH, protein, sediment

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

Necropsy: gross necropsy with collection of >50 tissues
Organ weights: brain, heart, testes, liver, lung, kidney, spleen, adrenal gland
Histopathology: heart, liver, spleen, kidney, adrenals of control and high dose animals; lungs of all animals; all macroscopically altered tissues.

Statistics:

Mann-Whitney U-test at significance levels of p = 0.05 and 0.01.

Results and discussion

Results of examinations

Details on results:

CLINICAL SIGNS AND MORTALITY
750 mg/kg bw: impaired general condition, emaciation, umkempt fur, increased mortality (1 male and 1 female; another female was killed in moribund state)
150/30 mg/kg bw: No effects on mortality were seen.

BODY WEIGHT, FOOD CONSUMPTION, WATER CONSUMPTION:
750 mg/kg bw: reduction of all 3 parameters (body weight gain: - 37% (males), - 13% (females); food consumption: - 29% (males), - 15% (females); water consumption: - 28% (males), - 12% (females).
150/30 mg/kg bw: No effect on body weight gain, food and water consumption was noted.

HAEMATOLOGY
750mg/kg, males only: statistically significant increases in RBC, Hb, Hct, and granulocyte counts; decreases in MCH, MCV, and lymphocytes.
No relevant changes were found in males at 150 mg/kg bw and in females at any dose group with the exception of one single female of the 150 mg/kg bw group showing anisocytosis and changes in red and white blood which were interpreted as a chance event by the study authors.

CLINICAL CHEMISTRY
750 mg/kg bw: increases in alkaline phosphatase activity (males only), and decreases of plasma albumin (both sexes) and triglyceride concentrations (males only).
150 mg/kg bw: no relevant findings

URINALYSIS
750 mg/kg bw: reduced urine volume in males;
150 mg/kg bw: no relevant findings


ORGAN WEIGHTS
750 mg/kg bw: increases in relative lung weights (males: +65%, females +69% as compared to the controls) and in absolute lung weights in females (+46%). Increases in relative adrenal weights (+33% in males, +30% in females), in relative kidney weights (+32% in males, +17% in females), and in relative liver weights (females only, +17%).
150 mg/kg bw: no effect on organ weights

GROSS PATHOLOGY:
750 mg/kg bw: lungs: brown stains in all animals that survived to the end of the study. The male that had died during the study showed dark lungs and yellow spots in the epididymides.

HISTOPATHOLOGY: NON-NEOPLASTIC
750 mg/kg bw:
lungs: focal inflammation (all males, 4 females), and fibrosis (4 males, 4 females); hyperplasia of bronchial epithelium in all animals. Foreign material was found in the lungs of 3/10 animals. In the animal that died during the study, sperm granulomas were noted in the epididymidis.
150 mg/kg bw: no pathological changes.
30 mg/kg bw: foreign material was found in the lung of a single animal, together with a minimal inflammatory response in the lung. As this effect was not noted in any other animal of this dose group the study authors assumed that it might have been caused by aspiration following an error in the gavage procedure.

Effect levels

Dose descriptor:

NOAEL

Effect level:

150 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Pathological and histopathological effects on the lung.

Target system / organ toxicity

Critical effects observed:

not specified