Bis(2-ethylhexyl) phthalate

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, acceptable with retrictions

Data source

Reference

Reference Type:

publication

Title:

Testicular toxicity of di(2-ethylhexyl) phthalate in developing rats.

Author:

Parmar, D., Srivastava, S.P., Srivastava, S.P.

Year:

1995

Bibliographic source:

Vet. Human. Toxicol. 37, 310-313.

Materials and methods

Principles of method if other than guideline:

Investigation of the activities of the testicular enzymes associated with spermatogenesis

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-ethylhexyl) phthalate

EC Number:

204-211-0

EC Name:

Bis(2-ethylhexyl) phthalate

Cas Number:

117-81-7

Molecular formula:

C24H38O4

IUPAC Name:

1,2-bis(2-ethylhexyl) benzene-1,2-dicarboxylate

Details on test material:

DEHP (purity not specified)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: groundnut oil

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

30 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 50, 100, 250 or 500 mg/kg
Basis:
actual ingested

No. of animals per sex per dose:

6 male rats per dose group

Control animals:

yes

Results and discussion

Effect levels

Dose descriptor:

LOAEL

Effect level:

50 mg/kg bw/day

Sex:

male

Basis for effect level:

other: effects on absolute and relative testis weight, and reduced testicular enzyme activities

Observed effects

There was an exposure-related and significant decrease of absolute and relative testicular weight at all dose levels.
From 50 mg/kg also a dose-dependent and significant increase in the activities of LDH and GGT was noted while that of SDH decreased.
β-glucuronidase increased at 250 or 500 mg DEHP/kg, while acid phosphatase decreased at the same dose levels.
The administration also resulted in marked destructive changes in the advanced germ cell layers and marked degrees of vacuolar degeneration in the testes at 250 and 500 mg/kg bw.
The significant alterations in the activities of SDH, LDH, and GGT occurred thus at much lower DEHP levels and prior to the histopathological changes. The Leydig cells and the fibroblasts appeared normal.

Applicant's summary and conclusion

Executive summary:

The activities of the testicular enzymes associated with spermatogenesis including LDH, GGT, SDH, β-glucuronidase, and acid phosphatase were studied in a similar study investigating the oral effect of DEHP on 25 day old male Wistar rats. Doses of 0, 50, 100, 250 or 500 mg/kg bw of DEHP (purity not specified) in groundnut oil were given for 30 consecutive days to 6 male rats per dose group. There was an exposure-related and significant decrease of absolute and relative testicular weight at all dose levels. From 50 mg/kg also a dose-dependent and significant increase in the activities of LDH and GGT was noted while that of SDH decreased. β-glucuronidase increased at 250 or 500 mg DEHP/kg, while acid phosphatase decreased at the same dose levels. The administration also resulted in marked destructive changes in the advanced germ cell layers and marked degrees of vacuolar degeneration in the testes at 250 and 500 mg/kg bw. The significant alterations in the activities of SDH, LDH, and GGT occurred thus at much lower DEHP levels and prior to the histopathological changes. The Leydig cells and the fibroblasts appeared normal.

A LOAEL for young rats of 50 mg/kg bw/day is derived from this study for effects on absolute and relative testies weight, and reduced testicular enzyme activities.