Tris(2-ethylhexyl) phosphate

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: No OECD study or GLP defined.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1983

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1985

Reference 3

Reference Type:

publication

Title:

Unnamed

Year:

1986

Reference 4

Reference Type:

other: Microfiche

Title:

Unnamed

Year:

1983

Reference 5

Reference Type:

other: microfiche

Title:

Unnamed

Year:

1900

Reference 6

Reference Type:

other: Microfiche

Title:

Unnamed

Year:

1984

Materials and methods

Principles of method if other than guideline:

other: oral repeated dose toxicity study in rats.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tris(2-ethylhexyl) phosphate

EC Number:

201-116-6

EC Name:

Tris(2-ethylhexyl) phosphate

Cas Number:

78-42-2

Molecular formula:

C24H51O4P

IUPAC Name:

tris(2-ethylhexyl) phosphate

Details on test material:

Purity of ca. 97-98%.

Test animals

Species:

rat

Strain:

other: F344/N

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: corn oil

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

5 d/w

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 250, 500, 1000, 2000 or 4000 mg/kg bw
Basis:
other: gavage

No. of animals per sex per dose:

10

Control animals:

other: yes (corn oil)

Details on study design:

Post-exposure period: no

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

no effects observed

Details on results:

Diminuated bw. of female rats beginning at the dose of 2000 mg/kg bw and in male rats beginning at the dose of 4000 mg/kg bw (5%); no substance-related histopathological findings.

Effect levels

1

Dose descriptor:

NOEL

Effect level:

ca. 1 000 mg/kg bw/day (nominal)

Sex:

female

Basis for effect level:

other: diminuated bw of female rats beginning at the dose of 2000 mg/kg bw .

2

Dose descriptor:

NOEL

Effect level:

ca. 2 000 mg/kg bw/day (nominal)

Sex:

male

Basis for effect level:

other: diminuated bw of male rats beginning at the dose of 4000 mg/kg bw .

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Survival and mean body weights of rats in the 13 weeks gavage studies:

		Mean Body Weights (grams)
Dose (mg/kg bw)	Survival*	Initial	Final	Change	Final Weight relative to Vehicle Controls *** (percent)
Male
0	**9/10	105	285	+ 180	--
250	10/10	106	292	+ 186	+ 2.5
500	10/10	107	304	+ 197	+ 6.7
1000	**8/10	106	302	+ 196	+ 6.0
2000	**7/10	108	300	+ 192	+ 5.3
4000	**9/10	105	270	+ 165	- 5.3
Female
0	10/10	101	179	+ 78	--
250	10/10	100	178	+ 78	- 0.6
500	10/10	102	176	+ 74	- 1.7
1000	10/10	100	177	+ 77	- 1.1
2000	**9/10	100	161	+ 61	-10.1
4000	**9/10	101	170	+ 69	- 5.0

* Number surviving/number per group

** Deaths were a result of gavage error

*** Final weight relative to vehicle controls= Fianal weight (Dosed group)* Final weight (Vehicle control) x 100

Final Weight (Vehicle Control)

Applicant's summary and conclusion

Executive summary:

In a 13 week oral repeated dose study male and female four-week-old F344/N rats were administered by gavage with the test substance (5 days per week). The study was conducted to evaluate the cumulative toxicity of the test substance and to determine the doses to be used in the 2 -year studies. Groups of rats of each sex were administered 0, 250, 500, 1000, 2000 or 4000 mg/kg bw. test substance, 5 days per week for 13 weeks by gavage. The animals were checked twice daily for signs of moribundity and mortality; moribund animals were killed. Animal weights were recorded weekly. At the end of the 13 -week studies, survivors were killed. Necropsies were performed on all animals, except those excessively autolyzed or cannibalized. No hematology or clinical biochemistry was performed. The following tissues were examined microscopically in vehicle controls, highest dose group, and all animals that died during the study: gross lesions and tissue masses, mandibular lymph node, salivary gland, sternebrae, including marrow, thyroid, parathyroids, small intestine, colon, liver, prostate/testes or ovaries/uterus, lungs and mainstem bronchi, mammary gland, skin, heart, esophagus, stomach, brain, thymus, trachea, pancreas, spleen, kidneys, adrenal glands, urinary bladder, pituitary, spinal cord if neurological signs were present, eyes if grossly abnormal. No compound related deaths, slight-moderate depression of weight gain at 2000 or 4000 mg/kg in female rats and at 4000 mg/kg bw. in male rats could be seen. No histopathologic effects could be observed. The NOEL in female rats was 1000 mg/kg bw. and 2000 mg/kg bw. in male animals .