2-ethylhexyl acetate

Specific investigations: other studies

Administrative data

Endpoint:

biochemical or cellular interactions

Type of information:

other: experimental result

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication/study report which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Effects of DEHP and five of its metabolites including 2-EH on rat testis in vivo and in vitro

GLP compliance:

not specified

Endpoint addressed:

toxicity to reproduction / fertility

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:

bis(2-ethylhexyl) phthalate

Details on test material:

- Name of test material (as cited in study report):

- 2-EH

- Other test substances examined in the same study:

DEHP
MEHP
Metabolite IX (mono-2-ethyl-hexanol-6-hexanoic acid)-phthalate; w-oxidation product of MEHP)
Metabolite VI (mono-2-ethyl-5-keto-hexanol)-phthalate
Metabolite V (mono-2-ethyl-5-hydroxy-hexanol)-phthalate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: propylene glycol (MEHP and MEHP-metabolites; DEHP and 2-EH: suspension without vehicle

Duration of treatment / exposure:

5 exposures

Frequency of treatment:

1/day

Doses / concentrations

Remarks:

Doses / Concentrations:
2.7 mmol/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

6 animals per test substance

Control animals:

yes, concurrent vehicle

Examinations

Examinations:

In vivo: metabolite blood levels (excluding 2-EH). Absolute and relative testes and prostate weight; degenerate dcells in seminiferous tubules.
In vitro: germ cell detachment in primary rat testicular cell cultures.

Results and discussion

Details on results:

Degeneration of testes and Sertoli cells were not associated with 2 -EH, but with MEHP, which is generated following the administration of DEHP.

Any other information on results incl. tables

In vivo: Five of six rats receiving MEHP had a much higher frequency of degenerating cells (degenerated spermatocytes and spermatids) in the seminiferous tubules, compared to the control animals or rats receiving DEHP, 2 -EH, or the metabolites of MEHP. Therefore, no testicular damage was observed in animas given 2 -EH.
In vitro: Germ cell detachment was significantly increased in primary rat testicular cell cultures when MEHP was adminsitered at concnetrations oft 1 µM and above (Table). DEHP and 2 -EH administered at 200 µM were not different from controls at 24 and 48 hours.

Applicant's summary and conclusion

Conclusions:

MEHP is the metabolite that is responsible for the testicular damage that is observed following administration of DEHP to rats.
2-EH has no adeverse effect on testis, germ cell detachment in vivo or in vitro.

Executive summary:

In was shown vivo and also in primary rat testicular cell cultures in vitro that MEHP was the metabolite that causes testicular damage following administration of DEHP. MEHP caused a significantly increased germ cell detachment in vitro at 1 µM and above, whereas effcts of 200 µM DEHP and 2 -EH were not different from controls after 24 or 48 hour incubation in vitro (Sjöberg et al., 1986).