2,3-epoxypropyl phenyl ether

Toxicity to reproduction

Administrative data

Endpoint:

two-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented study which meets basic scientific principles.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1975

Report date:

1975

Reference 2

Reference Type:

publication

Title:

The inhalation toxicity of phenylglycidyl ether: reproduction, mutagenic, teratogenic, and cytogenetic studies

Author:

Terrill JB, Lee KP, Culik R, Kennedy GL

Year:

1982

Bibliographic source:

Toxicology and applied pharmacology 64, 204-212

Reference 3

Reference Type:

publication

Title:

Unnamed

Year:

1974

Report date:

1974

Reference 4

Reference Type:

review article or handbook

Title:

Unnamed

Year:

1978

Report date:

1978

Reference 5

Reference Type:

secondary source

Title:

Phenyl glycidyl ether

Author:

MAK Commission

Year:

1991

Bibliographic source:

MAK List 1991

Report date:

1991

Materials and methods

Principles of method if other than guideline:

Male rats were exposed to either 0, 1, 5, or 12 ppm, 6 hours/day on 19 consecutive days. Afterwards these rats were mated with untreated female rats and the pups were examined for abnormalities. Litters were mated among each other and the next generation was again examined for abnormalities.

Test material

Test material information

Constituent 1

Reference substance name:

propane, 1,2-epoxy-3-phenoxy

IUPAC Name:

propane, 1,2-epoxy-3-phenoxy

Details on test material:

- Name of test material (as cited in study report): propane, 1,2-epoxy-3-phenoxy
No further information.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Age at study initiation: (P) 10 weeks
- Weight at study initiation: (P) Males: ca. 260 g (females not reported)
- Diet (ad libitum): Purina rat chow
- Water (ad libitum)
No further information.

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Chamber atmospheres were generated by syringe driving the liquid EPP into a heated (310°C) tube. The tube was housed in an oven and constructed in such a way that the nitrogen stream (10 liters/minute) which swept the vapors through the tube was the same temperature as the delivery tube. The exit port of the tube was connected to the top of a 4.5 m3 exposure chamber. Room air at 1,500 liters/minute was also drawn into the chamber at this point.

Details on mating procedure:

- M/F ratio per cage: 1/3
- Length of cohabitation: 5 days
- Proof of pregnancy: no data
- After successful mating each pregnant female was caged individually

Details on analytical verification of doses or concentrations:

Atmospheric samples were collected hourly in a midget impinger that contained 15 cc of 0:1 N NaOH in a 50:50 ethanol-water mixture. Analysis was performed by U.V. spectrophotometry at 270 nanometers.
- Samples taken from breathing zone: no data

Duration of treatment / exposure:

6 hours/day on 19 consecutive days (only F0 male animals)

Frequency of treatment:

daily

Details on study schedule:

- F1 parental animals not mated until 12 weeks post-weaning.

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 1, 5, 12 ppm
Basis:
nominal conc.
corresponding to ca. 0, 0.006, 0.03, 0.07 mg/l (calculated by Derelanko M, 2008)

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 1.75, 5.84, 11.2 ppm
Basis:
analytical conc.

No. of animals per sex per dose:

8

Control animals:

yes, sham-exposed

Details on study design:

The (potential) pregnancies were either terminated on the 18th day of gestation for examination of uterine contents, or continued through parturition. This determination was dependent upon the number of litters sired per male: if three dams were impregnated, two were allowed to deliver and one pregnancy was terminated on the 18th day; if two dams became pregnant, one was allowed to deliver, and one pregnancy was terminated; if one litter was sired, it continued through to parturition.

Positive control:

None.

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: No data

Oestrous cyclicity (parental animals):

No data.

Sperm parameters (parental animals):

Parameters examined in [all P, 8 of F1] male parental generations: testis weight, epididymis weight

Litter observations:

STANDARDISATION OF LITTERS
- Performed at birth: yes
- If yes, maximum of 8 pups/litter; excess pups were killed by random and discarded.

PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2] offspring:
[number and sex of pups, stillbirths, live births, weight gain, physical abnormalities]

GROSS EXAMINATION OF DEAD PUPS:
no

Postmortem examinations (parental animals):

SACRIFICE
Male animals (All surviving animals):
- F0 male animals were sacrificed following completion of the F0 mating trails
- 8 males of each week and group not employed during the F1 mating trials (12 weeks post weaning) and F1 parental males
- any animal appearing abnormal

Maternal animals (All surviving animals):
- each F0 female animal failing to conceive and each failing to deliver by the 23rd day of gestation
- 8 females of each week and group not employed during the F1 mating trials (12 weeks post weaning) and F1 parental females
- any animal appearing abnormal

GROSS NECROPSY
Yes

HISTOPATHOLOGY:
yes: reproductive organs of all the above mentioned animals (in addition, any tissue or organ noted abnormal during gross pathologic examination)

Postmortem examinations (offspring):

SACRIFICE
- The F1 offspring not selected as parental animals were sacrificed at weaning and all F2 offspring were sacrificed 2 weeks post-weaning.

The pups were examined for physical abnormalities and developmental/behavioral anomalies at birth, at weaning and 2 weeks post-weaning prior to their sacrifice.

Statistics:

Fisher’s exact test was used for comparison of treated versus control females for the fertility index. The Mann-Whitney U test was used for comparison of treated versus control for the number of corpora lutea, number of implantations, pre- or postimplantation losses, number of litters with early or late resorptions, and number of viable fetuses. Significance was assessed at the 0.05 probability level.

Reproductive indices:

Fertility index (number of matings (of 24) which resulted in pregancy), post implantation loss (number of implantations minus the number of viable fetuses)

Offspring viability indices:

Lactation index (number of pups alive at day 21 divided by the number retained at day 0)

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

one male rat from each treatment groups showed testicular atrophy (see details)

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

effects observed, treatment-related

Description (incidence and severity):

Groups treated with 2 or 11 ppm PGE: higher number of corpora lutea, implantations and viable fetuses than controls (as result of biological variation rather than treatment); significantly lower number of females pregnant in the 12-ppm group (see details)

Details on results (P0)

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
Statistically significant differences were observed in Week 5 where groups treated with either 2 or 12 ppm PGE had a higher number of corpora lutea, implantations, and viable fetuses than the controls. This isolated finding was probably the result of biological variation rather than treatment.
Also, the number of females pregnant in Week 1 in the 12-ppm-PGE group was significantly lower than that of the controls, but the lack of a consistent reduction makes the significance of the finding questionable, although the dose-time relationship may suggest some interference with reproduction capability. These effects were not considered as adverse.
Indices of fertility in the second matings were atypically low (30 to 40 %) in all groups (not further specified).

HISTOPATHOLOGY (PARENTAL ANIMALS)
One male rat (eight rats per group) from each of the three treatment groups (not further specified) showed testicular atrophy upon histopathologic examination. The gross appearance and weight of these testes did not suggest significant damage and the functional capacity for reproduction was demonstrated in these rats.

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

ca. 0.07 mg/L air (nominal)

Based on:

test mat.

Remarks:

corresponding to 12 ppm

Sex:

male

Basis for effect level:

other: Body weight, mortality, fertility (only males were treated)

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings:

not specified

Details on results (F1)

One F1 male pup, derived from the second week of mating with a male rat exposed to 2 ppm, exhibited a patch of curly hair, especially pronounced on the dorsal surface. This rat was subsequently mated with females of the same treatment group and week (not the same litter), and a proportion (approximately 20%) of the offspring had curly hair.

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

ca. 0.07 mg/L air (nominal)

Based on:

test mat.

Remarks:

corresponding to 12 ppm

Sex:

male/female

Basis for effect level:

other: Body weight, growth, gross structural anomalies, gross pathology (animals were not treated) one male pup, derived of mating with a male rat exposed to 2 ppm, exhibited a patch of curly hair, especially on the dorsal surface

Results: F2 generation

Effect levels (F2)

Dose descriptor:

NOAEL

Generation:

F2

Effect level:

ca. 0.07 mg/L air (nominal)

Based on:

test mat.

Remarks:

corresponding to 12 ppm

Sex:

male/female

Basis for effect level:

other: gross pathology

Overall reproductive toxicity

Reproductive effects observed:

not specified