Propene

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study, fully adequate for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.31 (Prenatal Developmental Toxicity Study)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Propene

EC Number:

204-062-1

EC Name:

Propene

Cas Number:

115-07-1

Molecular formula:

C3H6

IUPAC Name:

prop-1-ene

Constituent 2

Reference substance name:

Propylene

IUPAC Name:

Propylene

Details on test material:

- Name of test material (as cited in study report): propene
- Chemical name: propene
- Physical state: colourless gas
- Analytical purity: 99.53%
- Lot/batch No.: from Tank B 41
- Stability under test conditions: No changes were detected by gas chromatography over the in life phase of the study
- Storage condition of test material: gas cylinders stored in suitable containment outside the building

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Germany
- Strain: Wistar rats (CrlGlxBrlHan:WI)
- Age at study initiation: 70-84 days old. Supplied on day 0 post coitum (= detection of vaginal plug / sperm)
- Weight at study initiation: 142.7-173.4 g
- Housing: Singly from day 0 - 20 post coitum in type DK III stainless steel wire mesh cages (height: 15 cm, length: 37.5 cm,
width: 21 cm; floor area about 800 cm²)
- Diet: Ground Kliba rat/mouse/hamster laboratory diet (Provimi Kliba SA, Kaiseraugst, Switzerland) ad libitum (except during exposure)
- Water: Tap water ad libitum (except during exposure)

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24°C
- Humidity: 30-70%
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: From: 21 August 2001 To: 12 September 2001

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure (if applicable):

whole body

Vehicle:

other: conditioned air

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus / Method of holding animals in test chamber: The animals were kept singly in wire cages located in a glass-steel inhalation chamber with a volume of 1.4 m³
- Method of conditioning air: Charcoal filtered air conditioned to 50% ± 20% relative humidity and 22°C ± 2°C.
- Source and rate of air: Air conditioned supply air at 28 ± 2 m³/h
- System of generation : For each concentration, the test substance was supplied at a constant rate via the flow meter to a thermostat-controlled vaporizer (25 ± 5°C). There it was mixed with conditioned supply air and passed into the supply air of the inhalation system, where it was further diluted to the desired concentration.
- Air flow rate: 5-8, 22-38 and 245-377 L/h for groups exposed to 200, 1000 and 10000 ppm respectively

TEST ATMOSPHERE
- Brief description of analytical method used: Gas chromatography (in groups exposed to propene the constancy of concentration in each inhalation chamber was continuously monitored using total hydrocarbon analyzers).
- Samples taken from breathing zone: yes

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

For target concentrations of 200, 1000 and 10,000 ppm, the measured concentrations were determined to be 199.5±4.1, 1002±25 and 10010±197 ppm respectively with a nominal concentration of 205.2, 947 and 11593 ppm respectively. No propene was detected in the samples from the control chamber atmosphere.

Details on mating procedure:

- Impregnation procedure: purchased timed pregnant
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as day 0 of pregnancy

Duration of treatment / exposure:

14 days

Frequency of treatment:

6 hours/day

Duration of test:

day 6 through day 19 post coitum

No. of animals per sex per dose:

25

Control animals:

yes, sham-exposed

Details on study design:

Sex: female

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once during the chamber adaptation (preflow) period, on study day 0 and on post-exposure observation days and at least 3 times on exposure days (before, during and after exposure).

BODY WEIGHT: Yes
- Time schedule for examinations: study days 0, 1, 3, 6, 8, 10, 13, 15, 17, 19 and 20 p.c

FOOD CONSUMPTION: Yes
- Time schedule for examinations: study days 0, 1, 3, 6, 8, 10, 13, 15, 17, 19 and 20 p.c

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / No data
- Time schedule for examinations: study days 0, 1, 3, 6, 8, 10, 13, 15, 17, 19 and 20 p.c

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: ovaries, uterus

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: Conception rate and pre-and postimplantation losses were calculated

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: No data

Statistics:

Simultaneous comparison of all concentration groups with the control group using the Dunnett-test (2-sided). Pairwise comparison of each concentration group with the control group using FISHER'S EXACT test (one-sided) for the hypothesis of equal proportions. Pairwise comparison of each concentration group with the control group using the WILCOXON-test (one-sided) for the hypothesis of equal medians.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Effect levels (maternal animals)

1

Dose descriptor:

NOAEC

Effect level:

10 000 ppm (nominal)

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEC

Effect level:

10 000 ppm (nominal)

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:

NOAEC

Effect level:

10 000 ppm (nominal)

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

There were no substance-related effects on the dams concerning food and  water consumption, body weight, body weight change, uterine weights,  corrected body weight change, clinical and necropsy observations up to and including a concentration of 10,000 ppm.

There were no differences of toxicological relevance between the control and the substance exposed groups (200, 1,000 and 10,000 ppm) on the  gestational parameters, i.e. in conception rate, mean number of corpora  lutea, total implantations, resorptions and live foetuses, foetal sex ratio  or in the values calculated for the pre- and the postimplantation losses.  No substance-related differences were recorded for placental and foetal  body weights. The external, soft tissue and/or skeletal examinations of  the foetuses revealed no toxicological relevant differences between the  control and the substance-exposed groups.

Applicant's summary and conclusion

Conclusions:

The NOAEC for maternal and developmental toxicity to the Wistar rat is 10,000 ppm, a concentration of propene approaching the lower explosion limit.

Executive summary:

Under the conditions of this prenatal developmental toxicity study, the inhalation exposure of pregnant Wistar rats to propene from implantation to one day prior to the expected day of parturition (days 6 - 19 p .c .) elicited no maternal toxicity at any tested concentration up to 10,000 ppm, which is in the range of the lower explosion limit . There were no substance-induced, concentration-related influences on the gestational parameters and no signs of prenatal developmental toxicity, especially no substanceinduced indications of teratogenicity . Based on these results, the no observed adverse effect concentration (NOEC) for prenatal developmental and maternal toxicity from exposure to propene is 10,000 ppm .