Octane

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

key study

Study period:

24 Mar - 27 Apr 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

key study

Study period:

24 Mar - 27 Apr 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Species:

rat

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
There were no treatment related effects to mortality or pregnancy rates. In the 9000 ppm exposure group, there was a significant reduction in weight gain on GD 6-9, and GD 6-15, and slightly reduced on GD 9-12. In the 3000 ppm group, there was a significant reduction in weight gain on GD 9-12, but significantly increased on GD 18-21. Food consumption was significantly reduced in the 9000 ppm group on days 6-9, 9-12, 12-15, and 6-15. There were color changes in the lungs of females in the 9000 ppm group. These changes were also seen in one female each in the 0, 900 and 3000 ppm groups. The color changes in the 900 and 3000 ppm groups were not considered treatment related. There were no treatment related effects to gestational parameters.

Key result

Dose descriptor:

NOAEC

Effect level:

10 560 mg/m³ air (nominal)

Basis for effect level:

other: maternal toxicity

Key result

Dose descriptor:

LOAEC

Effect level:

31 680 mg/m³ air (nominal)

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
There were no treatment related effects to the development of fetuses.

Key result

Dose descriptor:

NOAEC

Effect level:

31 680 mg/m³ air (nominal)

Sex:

male/female

Basis for effect level:

other: developmental toxicity

Key result

Abnormalities:

not specified

Key result

Developmental effects observed:

not specified

Gestational Body Weight Changes (g)

	0.0 ppm	900.0 ppm	3000.0 ppm	9000.0 ppm
Day 0-6	28.21 (11.819)	31.55 (6.463)	31.19 (9.344)	29.36 (8.245)
Day 6-9	11.55 (8.103)	9.12 (6.009)	11.18 (4.539)	4.34 (6.029)
Day 9-12	16.02 (5.296)	16.31 (5.531)	11.33 (8.446)	12.65 (4.974)
Day 12-15	17.03 (6.807)	19.04 (4.473)	21.84 (9.577)	19.03 (6.453)
Day 15-18	43.52 (9.483)	41.27 (5.755)	37.83 (16.192)	44.11 (9.902)
Day 18-21	51.61 (15.190)	57.79 (8.681)	63.34 (11.295)	57.30 (12.247)
Day 6-15	44.59 (12.727)	44.47 (9.565)	44.35 (9.870)	36.02 (7.850)

Conclusions:

In rats, the maternal NOAEC was 3000 ppm, and the maternal LOAEC was 9000 ppm based on color changes in the lungs, reduced body weight gain, and reduced food consumption. The developmental NOAEC 9000 ppm in rats.

Executive summary:

This data is being read across from the source study that tested commercial hexane based on analogue read across.

The purpose of this study was to examine the developmental toxicity of commercial hexane in rats. Groups of 25 pregnant female rats were exposed to concentrations of 0, 900, 3000, or 9000 ppm for 6 hrs/day during gestational days 6 -15. The animals were then sacrificed on GD 21. During the study, the animals were examined for clinical signs, mortality, food and water consumption, and body weights taken. After sacrifice, the internal organs were examined, and the uterus was examined for viable fetuses, number of resorptions, and number of corpora lutea. Fetuses were examined for malformations. Necropsy revealed color changes in the lungs of females in the 9000 ppm groups along with reduced body weight gain, and reduced food consumption. No treatment related abnormalities was seen in the fetuses. The maternal NOAEC in rats was 3000 ppm, and the LOAEC 9000 ppm based on lung color changes, reduced body weight gain, and reduced food consumption. The developmental NOAEC in rats was 9000 ppm.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

commercial hexane

IUPAC Name:

commercial hexane

Details on test material:

- Name of test material (as cited in study report): commercial hexane
- Composition of test material, percentage of components: 52.19% n-hexane
- Analytical purity: no data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston, NY
- Age at study initiation: 63 days males, 56 days females at arrival
- Weight at study initiation: 250-300 g male, 175-200 g females
- Housing: individually in stainless steel wire mesh cages, identified with ear tags
- Diet (e.g. ad libitum): Prolab Certified Rodent Food, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 63-74 degree F
- Humidity (%): 40-71
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark


IN-LIFE DATES: From: April 9, 1989 To: April 21, 1989

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure (if applicable):

whole body

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 4320 l glass and stainless steel chambers.
- Method of holding animals in test chamber: cages
- Source and rate of air: 1000 l/min
- Method of conditioning air: Test substance was metered from a piston pump into one or two heated glass evaporators with a temperature of 27-70 degree C. Conditioned air was passed through the evaporators, where it carried the vapor into the exposure chamber.
- Temperature, humidity: monitored every 30 minutes
- Air flow rate: 1000 l/min
- Air change rate: 20 min, 14 air changes per hour
- Treatment of exhaust air: filtration


TEST ATMOSPHERE
- Brief description of analytical method used: GC with flame ionization detection
- Samples taken from breathing zone: yes, 7 times per exposure

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Samples were taken seven times per exposure period and analyzed with GC-FID. Distribution of test substance was evaluated by sampling five different areas of the exposure chamber.

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/1
- Length of cohabitation: April 2, 1989-April 6, 1989
- Proof of pregnancy: vaginal plug referred to as day 0

Duration of treatment / exposure:

gestation day (GD) 6-15

Frequency of treatment:

6 hrs/day

Duration of test:

GD 21

No. of animals per sex per dose:

25 pregnant females per exposure group

Control animals:

yes

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations: mortality, clinical signs

BODY WEIGHT: Yes
- Time schedule for examinations: GD 0, 6, 9, 12, 15, 18, 21

FOOD CONSUMPTION: Yes

WATER CONSUMPTION: Yes

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 21
- Organs examined: gravid uterus, ovaries, cervix, vagina, abdominal cavities, thoracic cavities, liver, kidneys

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: live and dead fetuses

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter were examined for thoracic and abdominal visceral abnormalities
- Skeletal examinations: Yes: half per litter

Statistics:

Quantitative continuous variables were compared by use of Levene's test for equal variance, analysis of variance, and t-tests with Bonferroni probabilities. Nonparametric data was evaluated using the Kruskal-Wallis test, followed by the Mann-Whitney U test. Indices were compared using Fisher's exact test. 0.05 was used as the criteria for statistical significance.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
There were no treatment related effects to mortality or pregnancy rates. In the 9000 ppm exposure group, there was a significant reduction in weight gain on GD 6-9, and GD 6-15, and slightly reduced on GD 9-12. In the 3000 ppm group, there was a significant reduction in weight gain on GD 9-12, but significantly increased on GD 18-21. Food consumption was significantly reduced in the 9000 ppm group on days 6-9, 9-12, 12-15, and 6-15. There were color changes in the lungs of females in the 9000 ppm group. These changes were also seen in one female each in the 0, 900 and 3000 ppm groups. The color changes in the 900 and 3000 ppm groups were not considered treatment related. There were no treatment related effects to gestational parameters.

Effect levels (maternal animals)

1

Key result

Dose descriptor:

NOAEC

Effect level:

10 560 mg/m³ air (nominal)

Basis for effect level:

other: maternal toxicity

2

Key result

Dose descriptor:

LOAEC

Effect level:

31 680 mg/m³ air (nominal)

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
There were no treatment related effects to the development of fetuses.

Effect levels (fetuses)

Key result

Dose descriptor:

NOAEC

Effect level:

31 680 mg/m³ air (nominal)

Sex:

male/female

Basis for effect level:

other: developmental toxicity

Fetal abnormalities

Key result

Abnormalities:

not specified

Overall developmental toxicity

Key result

Developmental effects observed:

not specified

Any other information on results incl. tables

Gestational Body Weight Changes (g)

	0.0 ppm	900.0 ppm	3000.0 ppm	9000.0 ppm
Day 0-6	28.21 (11.819)	31.55 (6.463)	31.19 (9.344)	29.36 (8.245)
Day 6-9	11.55 (8.103)	9.12 (6.009)	11.18 (4.539)	4.34 (6.029)
Day 9-12	16.02 (5.296)	16.31 (5.531)	11.33 (8.446)	12.65 (4.974)
Day 12-15	17.03 (6.807)	19.04 (4.473)	21.84 (9.577)	19.03 (6.453)
Day 15-18	43.52 (9.483)	41.27 (5.755)	37.83 (16.192)	44.11 (9.902)
Day 18-21	51.61 (15.190)	57.79 (8.681)	63.34 (11.295)	57.30 (12.247)
Day 6-15	44.59 (12.727)	44.47 (9.565)	44.35 (9.870)	36.02 (7.850)

Applicant's summary and conclusion

Conclusions:

In rats, the maternal NOAEC was 3000 ppm, and the maternal LOAEC was 9000 ppm based on color changes in the lungs, reduced body weight gain, and reduced food consumption. The developmental NOAEC 9000 ppm in rats.

Executive summary:

The purpose of this study was to examine the developmental toxicity of commercial hexane in rats. Groups of 25 pregnant female rats were exposed to concentrations of 0, 900, 3000, or 9000 ppm for 6 hrs/day during gestational days 6 -15. The animals were then sacrificed on GD 21. During the study, the animals were examined for clinical signs, mortality, food and water consumption, and body weights taken. After sacrifice, the internal organs were examined, and the uterus was examined for viable fetuses, number of resorptions, and number of corpora lutea. Fetuses were examined for malformations. Necropsy revealed color changes in the lungs of females in the 9000 ppm groups along with reduced body weight gain, and reduced food consumption. No treatment related abnormalities was seen in the fetuses. The maternal NOAEC in rats was 3000 ppm, and the LOAEC 9000 ppm based on lung color changes, reduced body weight gain, and reduced food consumption. The developmental NOAEC in rats was 9000 ppm.