Pent-1-ene

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

OECD 422 (read-across, GLP, Key, rel.1): NOAEC(fertility) = 18359 mg of but-1-ene /m3, ca. 22947 mg of pent-1-ene /m3

Link to relevant study records

Reference

Reference 1

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

Combined repeated exposure toxicity, reproduction and neurotoxicity screening in rats via whole-body inhalation exposures

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP compliant, guideline study, available as unpublished report, fully adequate for assessment

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: Crl:CD® (Sprague-Dawley) IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charles River Laboratories, Kingston, New York, USA.
- Age at study initiation: c.a. 8 weeks
- Weight at study initiation: Males 200-300g, females 150-250 g
- Housing: Individually in stainless steel, wire mesh cages within a 1.0 m3 glass and stainless steel whole body exposure chamber except during the mating period when one male and one female were housed together in a cage of suitable size.
- Diet: Certified Rodent Diet No. 5002 (PMI Nutrition International, St. Louis, MO, USA) ad libitum except during exposure
- Water: Mains water ad libitum except during exposure.
- Acclimation period: Approximately 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 20-25°C
- Humidity: 36-82%
- Air changes: Not reported
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 1 July 2002 To: 25 August 2002

Route of administration:

inhalation: gas

Type of inhalation exposure (if applicable):

whole body

Remarks on MMAD:

MMAD: 0.822 ± 0.1, 0.893 ± 0.2, 0.7986 ± 0.0343 and 3.6503 ± 7.0 for 0, 500, 2000 and 8000 ppm respectively
GSD: 2.019 ± 0.4, 1.869 ± 0.3, 1.893 ± 0.3 and 2.181 ± 0.8 for 0, 500, 2000 and 8000 ppm respectively

Vehicle:

air

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The whole-body exposure chambers each had a volume of approximately 1000 L. The chambers were operated at a minimum flow rate of 200 L/minute. The final airflow was set to provide at least one air change in 5.0 minutes (12 air changes/hour) and a T99 equilibrium time of at most 23 minutes At the end of the 6-hour exposure, all animals remained in the chambers for a minimum of 30 minutes. During this time, the chambers were operated at approximately the same flow rate using clean air only. The chambers were exhausted through the in housed filtering system, which consisted of a coarse filter, a HEPA filter and activated charcoal.
For the treated groups, the test article was delivered from the cylinder via a regulator with a backpressure gauge via 1/4" tubing through a flowmeter via 1/4" tubing. The outlet of the flowmeter was regulated by a built-in metering valve. The test article laden airstream was directed into the turret of a 1.0 m3 glass and stainless steel exposure chamber via 1/4" tubing, where it was diluted with room air as it was drawn into the chamber. For controls, room air was drawn into the turret of the 1.0 m3 glass and stainless steel exposure chamber.



TEST ATMOSPHERE
During each exposure, measurements of airborne concentrations were performed in the animals' breathing zone at least 4 times using an appropriate sampling procedure and on-line GC analytical method. During each week of exposure, particle size determinations were performed using a TSI Aerodynamic Particle Sizer to characterize the aerodynamic particle size distribution of any aerosol present.

Details on mating procedure:

- M/F ratio per cage: 1 male and 1 female
- Length of cohabitation: until evidence of mating seen or for 2 weeks
- Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged Individually

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The mean (± standard deviation) analytical (GC) concentrations for the control and the exposure groups were as follows: 0 ± 0, 524 ± 40, 2062 ± 126 and 8271 ± 683 ppm. The analytically measured exposure levels of the airborne test article were reasonably close to the targeted exposure levels.

Duration of treatment / exposure:

Two weeks prior to breeding, during breeding, and continuing through day 19 of gestation. The dams were then allowed to deliver their litters, which were retained until lactation day 4.

Frequency of treatment:

6 hours/day, 7 days/week

Details on study schedule:

see below

Dose / conc.:

0 ppm (nominal)

Remarks:

analytical: 0 ± 0 ppm

Dose / conc.:

500 ppm (nominal)

Remarks:

analytical: 524 ± 40 ppm

Dose / conc.:

2 000 ppm (nominal)

Remarks:

analytical: 2062 ± 126 ppm

Dose / conc.:

8 000 ppm (nominal)

Remarks:

analytical: 8271 ± 683 ppm

No. of animals per sex per dose:

12

Control animals:

yes, sham-exposed

Positive control:

None

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: At least twice/day

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Females weekly during pre-mating and on gestations days 0, 7, 14, 20 and lactation days 0, 1 and 4.

BODY WEIGHT: Yes
- Time schedule: Females day treatment initiated, twice/week until copulation confirmed, gestations days 0, 7, 14 and 20, lactation days 1 and 4. Females without evidence of mating were weighed weekly. All weighed at termination.

FOOD CONSUMPTION: Yes
- Time schedule: Females weekly during pre-mating period, gestation days 0-7, 7-14, 14-20 and lactation days 1-4.

Oestrous cyclicity (parental animals):

not determined

Sperm parameters (parental animals):

not determined

Litter observations:

STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: No

PARAMETERS EXAMINED
The following parameters were examined as soon as possible after parturition and twice/day thereafter: number of live and dead pups and sex of pups, physical or behavioural abnormalities.

GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities and presence/absence of milk in stomach

Postmortem examinations (parental animals):

SACRIFICE
- Maternal animals: Mated animals on day 5 post partum, animals when evidence of mating was detected but failed to deliver 26 days after evidence of mating, animals with no evidence of mating 26 days after completion of mating period.

GROSS NECROPSY
- Maternal animals: Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera. Number of implantation sites and corpora lutea were assessed.

ORGAN WEIGHTS
Maternal animals: ovaries with oviducts, uterus with vagina, adrenals, brain with brainstem, heart, kidneys, liver, thymus, spleen, lungs.

MICROSCOPIC EXAMINATION: No

Postmortem examinations (offspring):

External macroscopic postmortem examinations performed on all F1 pups found dead during lactation and at termination on lactation day 4. No microscopic examination of pups.

Statistics:

Mean values of all exposure groups were compared to the mean value for the control group at each time interval. For all parameters except for organ weights, the standard one-way analysis of variance (ANOVA) using the F ratio to assess significance was used. If significant differences among the means were indicated, additional testing was performed using Dunnett's t-test to determine which means were significantly different from the control. Organ weight data was analyzed only by parametric methods. Bartlett's test was performed to determine if groups had equal variances. The standard
one-way analysis of variance (ANOVA) using the F ratio to assess significance was used. If significant differences among the means were indicated, additional tests were used to determine which means were significantly different from the control: Dunnett's t-test for homogeneous data, or Cochran and Cox's modified t-test for non-homogeneous data. All t-tests were conducted at the 5% and 1% significance levels. For incidence data, a Fisher Exact Test with Bonferonni correction was performed to identify differences between the control and treatment groups.

Reproductive indices:

Gonadal function, mating behaviour, implantation, and general fertility were evaluated.

Offspring viability indices:

Litter size, pup survival, sex, body weight, and the presence of gross external malformations were assessed in the offspring.

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:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

not specified

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

see below

Key result

Dose descriptor:

NOAEC

Effect level:

8 000 ppm (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no treatment-related effects on dams at the highest concentration tested, no effects on reproductive performance or fertility

Remarks on result:

other: (18359 mg/m3, 18.4 mg/m3) nominal

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 examined

Gross pathological findings:

no effects observed

see below

Key result

Dose descriptor:

NOAEC

Generation:

F1

Effect level:

8 000 ppm (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no treatment-related effects on pups at the highest concentration tested, no effects on pup viability, body weight or development

Remarks on result:

other: (18359 mg/m3, 18.4 mg/L) nominal

Reproductive effects observed:

not specified

All mated female animals (except one animal in the 2000 ppm group) were found pregnant and delivered live pups. Mating indices for the male rats treated with the test article were comparable to controls. Mating, fertility and gestation indices for the female rats treated with the test article were comparable to controls. Most of the females mated at the first opportunity. There were also no treatment-related differences in the other reproductive parameters up to the time of parturition including the percent of females completing delivery and the duration of gestation, when compared to controls. There were no treatment related differences in all parturition parameters including the total number of pups delivered, the number of pups dying, the viability (4 day survival) index, the number of implantation sites and corpora lutea per dam, the pup sex ratio and the number of live pups/litter, when compared to controls.

Conclusions:

Under the test conditions, repeated inhalation exposure of 1-butene to female Sprague Dawley rats at levels of 0, 500, 2000, or 8000 ppm produced no evidence of adverse effects on any measures of reproductive function. Therefore, the NOAEC was 8000 ppm (18359 mg/m3).

Executive summary:

In a Combined Repeated dose toxicity study with Reproductive/Developmental toxicity screening Test performed according to the OECD Guideline No. 422 and in compliance with GLP, male and female rats were exposed by inhalation (whole body) to 1-butene at target concentrations of 500, 2000, 8000 ppm (1147, 4589, 18359 mg/m3) for two weeks prior to breeding, during breeding and until day 19 of gestation. The dams were then allowed to deliver their litters, which were retained until post-natal day 4.

There was no evidence of systemic toxicity in the parents.

There were no effects on mating behaviour, fertility and gestation indices, the number of implantation sites and corpora lutea per dam, numbers of pups delivered, viability of pups at and after birth and the pup sex ratio when compared to the control group.

Based on these data, the NOAEC for reproductive toxicity was the highest concentration tested 8000 ppm (18359 mg/m3).

There were no treatment-related effects on the development of pups. There were no effects on body weight gain or observed during macroscopic examination of pups at post mortem.

Based on these data, the NOAEC for developmental toxicity was also the highest concentration tested 8000 ppm (18359 mg/m3).

Reference 2

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

Combined repeated exposure toxicity, reproduction and neurotoxicity screening in rats via whole-body inhalation exposures

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

See RAAF document.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

read-across source

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:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

not specified

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

see below

Key result

Dose descriptor:

NOAEC

Effect level:

8 000 ppm (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no treatment-related effects on dams at the highest concentration tested, no effects on reproductive performance or fertility

Remarks on result:

other: ca. 22947 mg/m3 of pent-1-ene based on its MW of 70.1329 g/mol

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 examined

Gross pathological findings:

no effects observed

see below

Key result

Dose descriptor:

NOAEC

Generation:

F1

Effect level:

8 000 ppm (nominal)

Sex:

male/female

Basis for effect level:

other: no treatment-related effects on pups at the highest concentration tested, no effects on pup viability, body weight or development

Remarks on result:

other: ca. 22947 mg/m3 of pent-1-ene based on its MW of 70.1329 g/mol

Reproductive effects observed:

not specified

All mated female animals (except one animal in the 2000 ppm group) were found pregnant and delivered live pups. Mating indices for the male rats treated with the test article were comparable to controls. Mating, fertility and gestation indices for the female rats treated with the test article were comparable to controls. Most of the females mated at the first opportunity. There were also no treatment-related differences in the other reproductive parameters up to the time of parturition including the percent of females completing delivery and the duration of gestation, when compared to controls. There were no treatment related differences in all parturition parameters including the total number of pups delivered, the number of pups dying, the viability (4 day survival) index, the number of implantation sites and corpora lutea per dam, the pup sex ratio and the number of live pups/litter, when compared to controls.

Conclusions:

Under the test conditions and based on the read across approach, repeated inhalation exposure of pent-1-ene to female Sprague Dawley rats at levels of 0, 500, 2000, or 8000 ppm is expected to produce no evidence of adverse effects on any measures of reproductive function. Therefore, the NOAEC was 8000 ppm (22947 mg/m3 of pent-1-ene).

Executive summary:

In a Combined Repeated dose toxicity study with Reproductive/Developmental toxicity screening Test performed according to the OECD Guideline No. 422 and in compliance with GLP, male and female rats were exposed by inhalation (whole body) to 1-butene at target concentrations of 500, 2000, 8000 ppm (1147, 4589, 18359 mg/m3) for two weeks prior to breeding, during breeding and until day 19 of gestation. The dams were then allowed to deliver their litters, which were retained until post-natal day 4.

There was no evidence of systemic toxicity in the parents.

There were no effects on mating behaviour, fertility and gestation indices, the number of implantation sites and corpora lutea per dam, numbers of pups delivered, viability of pups at and after birth and the pup sex ratio when compared to the control group.

Based on these data, the NOAEC for reproductive toxicity was the highest concentration tested 8000 ppm (18359 mg/m3 of 1-butene, and ca.22947 mg/m3 of pent-1 -ene by read-across).

There were no treatment-related effects on the development of pups. There were no effects on body weight gain or observed during macroscopic examination of pups at post mortem.

Based on these data, the NOAEC for developmental toxicity was also the highest concentration tested 8000 ppm (18359 mg/m3of 1-butene, and ca. 22947 mg/m3 of pent-1 -ene by read-across).

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

22 947 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

The key study is GLP-compliant and of high quality (Klimish score = 1), performed on the analogue substance 1-butene. Based on the read across approach, this study was considered sufficiently robust to cover this endpoint.

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

A key study performed on an analogue of pent-1-ene was identified (Huntingdon, 2003). In a Combined Repeated dose toxicity study with Reproductive/Developmental toxicity screening Test performed according to the OECD Guideline No. 422 and in compliance with GLP, male and female rats were exposed by inhalation (whole body) to 1-butene at target concentrations of 500, 2000, 8000 ppm (1147, 4589, 18359 mg/m3) for two weeks prior to breeding, during breeding and until day 19 of gestation. The dams were then allowed to deliver their litters, which were observed until post-natal day 4.

There was no evidence of systemic toxicity in the parents.

There were no effects on mating behaviour, fertility and gestation indices, the number of implantation sites and corpora lutea per dam, numbers of pups delivered, viability of pups at and after birth and the pup sex ratio when compared to the control group.

Based on these data, the NOAEC for fertility/reproductive toxicity was the highest concentration tested 8000 ppm (18359 mg/m3 of 1-butene, and ca.22947 mg/m3 of pent-1-ene by read-across).

Moreover, in the NTP 14 -week studies, mice and rats were exposed by whole body inhalation to the analogue substance isobutene at concentrations up to 8,000 ppm (6 hours per day, 5 days per week). There were no effects on female reproductive parameters and the effects on male reproductive parameters observed at the highest dose were very minor, and were not considered to be of biological relevance. Furthermore, the incidence of nonneoplastic lesions in male and in female rats in the 2 -year inhalation study of isobutene was not increased.

Effects on developmental toxicity

Description of key information

OECD 422 (read-across, GLP, supp, rel.1): NOAEC(development) = 18359 mg of but-1-ene /m3, ca. 22947 mg of pent-1-ene /m3

Link to relevant study records

Reference

Reference 1

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: Crl:CD® (Sprague-Dawley) IGS BR

Details on test animals or test system and environmental conditions:

- Source: Charles River Laboratories, Kingston, New York, USA.
- Age at study initiation: c.a. 8 weeks
- Weight at study initiation: Males 200-300g, females 150-250 g
- Housing: Individually in stainless steel, wire mesh cages within a 1.0 m3 glass and stainless steel whole body exposure chamber except during the mating period when one male and one female were housed together in a cage of suitable size.
- Diet: Certified Rodent Diet No. 5002 (PMI Nutrition International, St. Louis, MO, USA) ad libitum except during exposure
- Water: Mains water ad libitum except during exposure.
- Acclimation period: Approximately 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 20-25°C
- Humidity: 36-82%
- Air changes: Not reported
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 1 July 2002 To: 25 August 2002

Route of administration:

inhalation: gas

Type of inhalation exposure (if applicable):

whole body

Vehicle:

air

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The whole-body exposure chambers each had a volume of approximately 1000 L. The chambers were operated at a minimum flow rate of 200 L/minute. The final airflow was set to provide at least one air change in 5.0 minutes (12 air changes/hour) and a T99 equilibrium time of at most 23 minutes At the end of the 6-hour exposure, all animals remained in the chambers for a minimum of 30 minutes. During this time, the chambers were operated at approximately the same flow rate using clean air only. The chambers were exhausted through the in housed filtering system, which consisted of a coarse filter, a HEPA filter and activated charcoal.
For the treated groups, the test article was delivered from the cylinder via a regulator with a backpressure gauge via 1/4" tubing through a flowmeter via 1/4" tubing. The outlet of the flowmeter was regulated by a built-in metering valve. The test article laden airstream was directed into the turret of a 1.0 m3 glass and stainless steel exposure chamber via 1/4" tubing, where it was diluted with room air as it was drawn into the chamber. For controls, room air was drawn into the turret of the 1.0 m3 glass and stainless steel exposure chamber.



TEST ATMOSPHERE
During each exposure, measurements of airborne concentrations were performed in the animals' breathing zone at least 4 times using an appropriate sampling procedure and on-line GC analytical method. During each week of exposure, particle size determinations were performed using a TSI Aerodynamic Particle Sizer to characterize the aerodynamic particle size distribution of any aerosol present.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The mean (± standard deviation) analytical (GC) concentrations for the control and the exposure groups were as follows: 0 ± 0, 524 ± 40, 2062 ± 126 and 8271 ± 683 ppm. The analytically measured exposure levels of the airborne test article were reasonably close to the targeted exposure levels.

Details on mating procedure:

- M/F ratio per cage: 1 male and 1 female
- Length of cohabitation: until evidence of mating seen or for 2 weeks
- Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged Individually

Duration of treatment / exposure:

Two weeks prior to breeding, during breeding, and continuing through day 19 of gestation. The dams were then allowed to deliver their litters, which were retained until lactation day 4.

Frequency of treatment:

6 hrs/day, 7 days/week

Duration of test:

After an initial exposure period of 2 weeks, males and females were mated for 1 week. Females were allowed to litter and to rear their progeny until day 4 of lactation; after which the parent animals and the pups were killed

Dose / conc.:

500 ppm (nominal)

Dose / conc.:

2 000 ppm (nominal)

Dose / conc.:

8 000 ppm (nominal)

No. of animals per sex per dose:

12

Control animals:

yes, sham-exposed

Details on study design:

none

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: At least twice/day

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Females weekly during pre-mating and on gestations days 0, 7, 14, 20 and lactation days 0, 1 and 4.

BODY WEIGHT: Yes
- Time schedule: Females day treatment initiated, twice/week until copulation confirmed, gestations days 0, 7, 14 and 20, lactation days 1 and 4. Females without evidence of mating were weighed weekly. All weighed at termination.

FOOD CONSUMPTION: Yes
- Time schedule: Females weekly during pre-mating period, gestation days 0-7, 7-14, 14-20 and lactation days 1-4.

SACRIFICE
- Maternal animals: Mated animals on day 5 post partum, animals when evidence of mating was detected but failed to deliver 26 days after evidence of mating, animals with no evidence of mating 26 days after completion of mating period.

Ovaries and uterine content:

GROSS NECROPSY
- Maternal animals: Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera. Number of implantation sites and corpora lutea were assessed.

ORGAN WEIGHTS
Maternal animals: ovaries with oviducts, uterus with vagina, adrenals, brain with brainstem, heart, kidneys, liver, thymus, spleen, lungs.

Fetal examinations:

STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: No

PARAMETERS EXAMINED
The following parameters were examined as soon as possible after parturition and twice/day thereafter: number of live and dead pups and sex of pups, physical or behavioural abnormalities.

GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities and presence/absence of milk in stomach

Postmortem examinations (Offspring)
External macroscopic postmortem examinations performed on all F1 pups found dead during lactation and at termination on lactation day 4. No microscopic examination of pups.

Statistics:

Mean values of all exposure groups were compared to the mean value for the control group at each time interval. For all parameters except for organ weights, the standard one-way analysis of variance (ANOVA) using the F ratio to assess significance was used. If significant differences among the means were indicated, additional testing was performed using Dunnett's t-test to determine which means were significantly different from the control. Organ weight data was analyzed only by parametric methods. Bartlett's test was performed to determine if groups had equal variances. The standard
one-way analysis of variance (ANOVA) using the F ratio to assess significance was used. If significant differences among the means were indicated, additional tests were used to determine which means were significantly different from the control: Dunnett's t-test for homogeneous data, or Cochran and Cox's modified t-test for non-homogeneous data. All t-tests were conducted at the 5% and 1% significance levels. For incidence data, a Fisher Exact Test with Bonferonni correction was performed to identify differences between the control and treatment groups.

Reproductive indices
Gonadal function, mating behaviour, implantation, and general fertility were evaluated.

Offspring viability indices
Litter size, pup survival, sex, body weight, and the presence of gross external malformations were assessed in the offspring.

Indices:

none

Historical control data:

not cited

Details on maternal toxic effects:

Maternal toxic effects: no effects

Details on maternal toxic effects: no effects

Key result

Dose descriptor:

NOAEC

Effect level:

8 000 other: ppm (18,359 mg/m3, 18.4 mg/L) nominal

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Abnormalities:

not specified

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects: no effects

Details on embryotoxic / teratogenic effects: no effects

Key result

Dose descriptor:

NOAEC

Effect level:

8 000 other: ppm (18,359 mg/m3, 18.4 mg/L) nominal

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: developmental toxicity

Abnormalities:

not specified

Developmental effects observed:

not specified

BODY WEIGHT AND WEIGHT GAIN (PARENTS)

No effects

BODY WEIGHT (OFFSPRING)

No effects

Conclusions:

No effects on or pup development were seen when male and female rats were exposed to 1-butene at concentrations of 500, 2000, or 8000 ppm for two weeks prior to breeding, during breeding and until day 19 of gestation. The NOAEC for reproductive and developmental toxicity was 8000 ppm (18,359 mg/m3), the highest concentration tested.

Executive summary:

Male and female rats were exposed to 1-butene at target concentrations of 500, 2000, 8000 ppm (1147, 4589, 18,359 mg/m3) for two weeks prior to breeding, during breeding and until day 19 of gestation. The dams were then allowed to deliver their litters, which were retained until post-natal day 4. There was no evidence of significant systemic toxicity in the parents. There were no treatment-related effects on the development of pups. There were no effects on body weight gain or observed during macroscopic examination of pups at post mortem.

Under the test conditions, the NOAEC for reproductive and developmental toxicity was 8000 ppm (18,359 mg/m3), the highest concentration tested.

Reference 2

Endpoint:

developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

See RAAF Document.

Reason / purpose for cross-reference:

read-across source

Details on maternal toxic effects:

Maternal toxic effects: no effects

Details on maternal toxic effects: no effects

Key result

Dose descriptor:

NOAEC

Effect level:

8 000 ppm (nominal)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Remarks on result:

other: ca. 22947 mg/m3 of pent-1-ene based on its MW of 70.1329 g/mol

Abnormalities:

not specified

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects: no effects

Details on embryotoxic / teratogenic effects: no effects

Key result

Dose descriptor:

NOAEC

Effect level:

8 000 ppm (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: developmental toxicity

Remarks on result:

other: ca. 22947 mg/m3 of pent-1-ene based on its MW of 70.1329 g/mol

Abnormalities:

not specified

Developmental effects observed:

not specified

BODY WEIGHT AND WEIGHT GAIN (PARENTS)

No effects

BODY WEIGHT (OFFSPRING)

No effects

Conclusions:

No effects on or pup development were seen when male and female rats were exposed to 1-butene at concentrations of 500, 2000, or 8000 ppm for two weeks prior to breeding, during breeding and until day 19 of gestation. The NOAEC for reproductive and developmental toxicity was 8000 ppm (18,359 mg/m3), ca. 22947 mg/m3 of pent-1-ene.

Executive summary:

Male and female rats were exposed to 1-butene at target concentrations of 500, 2000, 8000 ppm (1147, 4589, 18,359 mg/m3) for two weeks prior to breeding, during breeding and until day 19 of gestation. The dams were then allowed to deliver their litters, which were retained until post-natal day 4. There was no evidence of significant systemic toxicity in the parents. There were no treatment-related effects on the development of pups. There were no effects on body weight gain or observed during macroscopic examination of pups at post mortem.

Under the test conditions, the NOAEC for reproductive and developmental toxicity was 8000 ppm (18,359 mg/m3 of 1-butene), the highest concentration tested, ca. 22947 mg/m3 of pent-1-ene by read-across.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

22 947 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

The study is GLP-compliant and of high quality (Klimish score = 1), performed on the analogue substance 1-butene. Based on the read across approach, this study was considered sufficiently robust to cover this endpoint.

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

A study performed on an analogue of pent-1-ene was identified (Huntingdon, 2003). In a Combined Repeated dose toxicity study with Reproductive/Developmental toxicity screening Test performed according to the OECD Guideline No. 422 and in compliance with GLP, male and female rats were exposed by inhalation (whole body) to 1-butene at target concentrations of 500, 2000, 8000 ppm (1147, 4589, 18359 mg/m3) for two weeks prior to breeding, during breeding and until day 19 of gestation. The dams were then allowed to deliver their litters, which were observed until post-natal day 4.

There was no evidence of systemic toxicity in the parents.

There were no treatment-related effects on the development of pups. There were no effects on body weight gain or observed during macroscopic examination of pups at post mortem.

Based on these data, the NOAEC for developmental toxicity was also the highest concentration tested 8000 ppm (18359 mg/m3of 1-butene, and ca. 22947 mg/m3 of pent-1-ene by read-across).

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the regulation (EC) No. 1272/2008.

 

Self-classification:

The substance is not considered to have adverse effects on reproduction or development based on the results of studies performed on valid supporting substances. Classification of the substance for this endpoint is not justified in the absence of treatment-related effect according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.