Ethylbenzene

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: other: NTP protocol

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

Ethylbenzene

EC Number:

202-849-4

EC Name:

Ethylbenzene

Cas Number:

100-41-4

Molecular formula:

C8H10

IUPAC Name:

ethylbenzene

Details on test material:

as prescribed by 1.1 - 1.4

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Species/strain: Mouse BCC3F1
- Number of animals: 50M+50F/dose level
- Source: Simonsen Laboratories, Inc., Gilroy, CA
- Age at study initiation: 6 weeks at start of study
- Weight at study initiation: M 22.3-23.0 g; F 18.0-18.6 g g (Range of average weights reported for week 1)
- Housing: individually housed in stainless steel cages
- Diet: NIH-07 open formula pelleted diet (Zeigler Brothers Inc., Gardners, PA), ad libitum except during exposure
- Water: untreated course-filtered City of Chicago water, ad libitum except during exposure

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure (if applicable):

whole body

Vehicle:

other: air

Details on exposure:

GENERATION OF TEST ATMOSPHERE/CHAMBER DESCRIPTION
- Chambers: Stainless steel chambers
- Exposure apparatus: Flash evaporator units
- Chamber concentrations: Actual mean exposure concentrations achieved in the chambers throughout the study were 75.2, 248 and 748 ppm ethylbenzene.

TEST SUBSTANCE
Ethylbenzene was used from two lots: A060989 and A051890; A060989 had an overall purity > 99% and contained 62 +/- 3.1 ppm cumene; lot A051890 also had an overall purity of > 99%. Concentration of peroxide ranged from 1.12 to 10.7 ppm

TEST ATMOSPHERE
- Concentration: monitored by an automatic sampling system coupled to a gas chromatograph equipped with a flame ionization detector. Each study chamber atmosphere was analyzed hourly during the 6 hour exposure.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

104 weeks

Frequency of treatment:

6 hours/day, 5 days/week

Duration of test:

104 weeks

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
75 ppm (325 mg/m3)
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
250 ppm (1084 mg/m3)
Basis:
nominal conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
750 ppm (3251 mg/m3)
Basis:
nominal conc.

No. of animals per sex per dose:

50M+50F/dose level

Control animals:

yes

Details on study design:

50M+50F/dose level
Post exposure period:None

Statistics:

Statistical analyses for possible dose-related effects on survival used Cox's method for testing two groups for equality and Tarone's life table test to identify dose-related trends. The incidences of neoplasms and nonneoplastic lesions were calculated as were the survival-adjusted neoplasm rate for each group and each site-specific neoplasm. The majority of the neoplasms in these studies were considered incidental to the cause of death or not rapidly lethal. Thus the primary statistical method used was logistic regression analysis, which assumed that the diagnosed neoplasm were discovered as the result of death from an unrelated cause and thus did not affect the risk of death. Neoplastic prevalence was modeled as a logistic function of chemical exposure and time. The neoplasm incidences of exposed and control groups were compared on the basis of the likelihood score test for the regression coefficient of dose. In addition to logistic regression other methods employed were the life table test appropriate for rapidly lethal neoplasms, and the Fisher exact test and the Cochran-Armitage trend test, procedures based on the overall proportion of neoplasm-bearing animals. Tests of significance included pair wise comparisons of each exposed group with controls and a test for an overall dose related trend. For the analysis of nonneoplastic lesions, the primary statistical analysis used was a logistic regression analysis in which nonneoplastic lesion prevalence was modeled as a logistic function of chemical exposure and time. Average severity values were analyzed for significance with the Mann-Whitney test.

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Effect level:

750 ppm

Sex:

male/female

Basis for effect level:

other: Overall effects

Observed effects

MORTALITY AND TIME TO DEATH:
Survival of exposed groups of male and female mice was similar to that of the chamber controls. No clinical findings were attributed to ethylbenzene exposure. Mean survival for male mice was 636 days in controls, 684, 692 and 665 days for 75, 250 and 750 ppm groups respectively. In females the mean survial was 689, 700, 701 and 692 days for 75, 250 and 750 ppm groups respectively.

BODY WEIGHTS: Mean body weights of female mice exposed to 75 ppm, were greater (about 6%) than those of the chamber controls from week 72 until the end of the study. Mean body weights of 750 ppm females were generally less than those of the chamber controls from week 24 through week 68 but were similar to those of the chamber control from week 72 until the end of the study. Mean body weights of male mice were similar to controls throughout the study

CLINICAL FINDINGS: No clinical findings were attributed to ethylbenzene exposure.

HISTOPATHOLOGY: Test article-related organ pathology was present in the lung, liver, thyroid gland and pituitary gland of ethylbenzene exposed mice. There were no treatment related effects on the reproductive organs

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:

Ethylbenzene at atmosphric concentrations up to 750 ppm for 2 years had no adverse effect on the reproductive organs of male or female mice as determined by histopathological examination.

Executive summary:

Refer to section 7.5.2. Repeated dose toxicity: inhalation: KS_NTP_1999_104 Week Inhalation Mice

Ethylbenzene at atmosphric concentrations up to 750 ppm for 2 years had no adverse effect on the reproductive organs of male or female mice as determined by histopathological examination.