Tris(2-ethylhexyl) phosphate

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: No OECD guideline or GLP defined.

Data source

Reference

Reference Type:

publication

Title:

Toxicological Studies on Tri-(2-Ethylhexyl)-Phosphate

Author:

MacFarland H.N.; Punte C.L.

Year:

1966

Bibliographic source:

Archives of Environmental Health Vol. 13, pp.13-20

Materials and methods

Principles of method if other than guideline:

other: repeated dose toxicity inhalation study in guinea pigs

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:

Mol wt: 434.6;
Sp g: 0.925 at 20 C;
n25D: 1.4473;
Surface tension: 31 dynes/sq cm;
Viscosity: 10.2 cp;
Vap press: 2 mm Hg at 200 C

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: no data

Remarks on MMAD:

MMAD / GSD: 3.8µ, with a geometric standard deviation of 1.7

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

3 months

Frequency of treatment:

6h/d, 5d/w

Doses / concentrations

Remarks:

Doses / Concentrations:
1.6 and 9.6 mg/m³
Basis:
analytical conc.

No. of animals per sex per dose:

20

Control animals:

yes

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:

effects observed, treatment-related

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Effect levels

Dose descriptor:

NOAEC

Effect level:

ca. 9.6 mg/m³ air

Sex:

male

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

RS-Freetext:
at high level significantly increased terminal body weight,
no significant alteration in red blood cell and plasma
cholinesterase activity, no abnormalties at necropsy,
microscopic examination revealed inconsistent and
reversible changes of renal parenchyma of the high level
group, sections of the spinal cord and sciatic nerve stained
to demonstrate the myelin sheaths showed no pathologic
alteration.

Applicant's summary and conclusion

Executive summary:

In an old and limited documented 3 month repeated inhalation study in guinea pigs performed in the same laboratory two different concentrations of test substance aerosol were used in three chambers ( 1.6 and 9.6 mg/m³); the third served as control. The animals were exposed for six hours a day, five days per week, to a total of 60 exposures. Two deaths were recorded, one in the control and one in the low level test substance group; both deaths occurred during the ninth week of exposure. The only gross sign observed was piloerection, seen in both control and treated groups throughout the 12 -week period. Body weights decreased in all three groups during the first week of exposure but steadily increased in the succeeding weeks. The mean kidney weight to body weight ratio for both test substance groups was significantly lower than that of the control group. No significant differences were found in the red blood cell and plasma cholinesterase activities between the control group and either of the treated groups. Gross pathological examination of the two guinea pigs which died during the ninth week of exposure showed extensive consolidation of lung tissue. When the surviving animals were sacrificed at the end of the 12 week´s exposure, midly congested lungs were noted in a quarter of the guinea pigs in the control group, but no abnormalities were found in the test substance treated animals. Microscopic examination of the tissue revealed only inconsistent and apparently reversible changes in the renal parenchyma of the high level test substance groups. Histopathological alterations in the lung and liver were confined to those due to coincidental disease. Sections of the spinal cord and sciatic nerve stained to demonstrate the myelin sheaths showed no pathologic alteration.