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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: 28 d repeated dose study
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Principles of method if other than guideline:
Bis(2-ethylhexyl) hydrogen phosphate was administered by gavage to 5 male and 5 female Wistar rats per dose group in daily doses of 0, 30, 150 or 750 mg/kg bw for 28 days to asses its toxicity. At the end of the treatment period all animals were killed and necropsied. The pathologic evaluation consisted of organ weight, gross and microscopic examination of reproductive organs, incl. testes, epididymis, prostate gland, seminal vesicle, vagina, cervix, uterus, ovary/oviduct.
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(2-ethylhexyl) hydrogen phosphate
EC Number:
206-056-4
EC Name:
Bis(2-ethylhexyl) hydrogen phosphate
Cas Number:
298-07-7
Molecular formula:
C16H35O4P
IUPAC Name:
bis(2-ethylhexyl) hydrogen phosphate
Test material form:
other: liquid
Details on test material:
Purity 99.3%
Appearance Colorless liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on mating procedure:
not applicable - 28 day repeated dose study
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 30, 150, or 750 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
5 male and 5 female rats/dose
Control animals:
yes, concurrent vehicle

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

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Dose descriptor:
NOAEL
Effect level:
150 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: At a dose of 750 mg/kg bw/day, weight of seminal vesicles was reduced an a minimally increased proportion of round spermatides in the epididymides was noted
Dose descriptor:
NOAEL
Effect level:
> 750 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: No findings on female reproduction organs were reported

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Daily oral treatment of rats with bis(2-ethylhexyl) hydrogen phosphate at doses of 0, 30, 150, 750 mg/kg bw for a period of 4 weeks resulted in effects in the alimentary tract (hyper- and parakeratosis, edema, gastritis, erosions and ulcers), partially leading to peritonitis, partly starting at the low dose of 30 mg/kg bw/day and indicating a local irritating and corrosive effect of bis(2-ethylhexyl) hydrogen phosphate.

At the dose of 750 mg/kg bw/day, weight of seminal vesicles was decreased correlating to reduced secretion in the prostate and seminal vesicle at histopathology. Additionally, a minimally increased proportion of round spermatids in the epididymides was noted in male animals after 750 mg/kg. These findings might indicate a primary systemic effect but also it is more likely that they reflect delayed sexual maturation as a sequel of poor condition of these animals. No other findings were reported for male reproduction organs. In female rats no changes (organs weights, gross or histopahtological changes) concerning the the reproduction organs were noted.

Applicant's summary and conclusion

Executive summary:

Bis(2-ethylhexyl) hydrogen phosphate was administered by gavage to 5 male and 5 female Wistar rats per dose group in daily doses of 0, 30, 150 or 750 mg/kg bw for 28 days to asses its toxicity. At the end of the treatment period all animals were killed and necropsied. The pathologic evaluation consisted of organ weight, gross and microscopic examination of reproductive organs, incl. testes, epididymis, prostate gland, seminal vesicle, vagina, cervix, uterus, ovary/oviduct.

At the dose of 750 mg/kg bw/day, weight of seminal vesicles was decreased correlating to reduced secretion in the prostate and seminal vesicle at histopathology. Additionally, a minimally increased proportion of round spermatids in the epididymides was noted in male animals after 750 mg/kg. These findings might indicate a primary systemic effect but also it is more likely that they reflect delayed sexual maturation as a sequel of poor condition of these animals. No other findings were reported for male reproduction organs. In female rats no changes (organs weights, gross or histopahtological changes) concerning the the reproduction organs were noted.

Due to the decreased weight in seminal vesicels correlating to reduced secretion in the prostate and seminal vesicle at histopathology and the minimally increased proportion of round spermatides in the epididymides a NOAEL of > 150 mg/kg bw/day is assumed for male rats.

This assumption includes that this findings indicate a primary systemic effects. However, it is more likely that they reflect delayed sexual maturation as a sequel of poor condition of these animals due to the effects in the alimentary tract caused by the local irritant and corrosive properties of bis(2-ethylhexyl) hydrogen phosphate.

No effects were reported for female reproduction organs at the highest applied dose. Therefore for female rats a NOAEL of > 750 mg/kg bw/day for reproduction is justified.