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Toxicological information

Specific investigations: other studies

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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

Constituent 1
Chemical structure
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).

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