Hydrocarbons, C4

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

other: EU Risk Assessment

Adequacy of study:

other information

Reliability:

other:

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference 1

Reference Type:

other: EU Risk Assessment

Title:

European Union Risk Assessment Report 1,3-BUTADIENE, CAS No: 106-99-0, EINECS No:203-450-8

Author:

[ECB] European Chemicals Bureau

Year:

2002

Reference 2

Reference Type:

review article or handbook

Title:

Overview of reproductive and developmental toxicity studies of 1,3-butadiene in rodents.

Author:

Morrissey, R.E.

Year:

1990

Bibliographic source:

Environ Health Persp. 86; 79-84.

Reference 3

Reference Type:

study report

Title:

Unnamed

Year:

1988

Reference 4

Reference Type:

publication

Title:

Ovarian toxicity and carcinogenicity in eight recent National Toxicology Program studies.

Author:

Maronpot, R.R.

Year:

1987

Bibliographic source:

Environ Health Persp. 73; 125-130.

Reference 5

Reference Type:

publication

Title:

Multiple organ carcinogenicity of 1,3-butadiene in B6C3F1 mice after 60 weeks of inhalation exposure.

Author:

Huff, et al.

Year:

1985

Bibliographic source:

Science. 227; 548-549.

Reference 6

Reference Type:

publication

Title:

Toxicology and carcinogenesis studies of 1,3-butadiene in B6C3F1 mice (inhalation studies).

Author:

NTP

Year:

1993

Bibliographic source:

NTP Technical Report Series no 434, NIH Publication 93-3165, Research Triangle Park, NC, USA

Materials and methods

Principles of method if other than guideline:

EU Risk Assessment on the major component of C4 Hydrocarbons: 1,3-Butadiene

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

Buta-1,3-diene

EC Number:

203-450-8

EC Name:

Buta-1,3-diene

Cas Number:

106-99-0

Molecular formula:

C4H6

IUPAC Name:

buta-1,3-diene

Details on test material:

- Name of test material (as cited in study report): 1,3-butadiene
- CAS number: 106-99-0
- EINECS number: 203-450-8

Test animals

Species:

mouse

Administration / exposure

Route of administration:

inhalation: gas

Results and discussion

Any other information on results incl. tables

A sperm-head morphology assay was conducted in mice (Hackett et al., 1988a). Details of the study are provided by Morissey et al. (1990).

Groups of 20 male mice were exposed to 0, 200, 1,000 or 5,000 ppm butadiene 6 hours/day for 5 days and sacrificed in the fifth week postexposure. Mice were examined for lesions of the reproductive tract and for gross tissue abnormalities. At least 500 sperm heads per mouse were examined for morphological abnormalities. Transient signs of toxicity, piloerection and dyspnea, were observed immediately following exposure to 5,000 ppm butadiene, but there were no mortalities and no effect on bodyweight in any groups compared with control.

There was a concentration- related increase in the percentage of abnormal sperm in exposed mice, with an increase of 21% in abnormal sperm at 200 ppm, 73% at 1,000 ppm and 129% at 5,000 ppm, relative to controls. The increases at 1,000 and 5,000 ppm were statistically significant.

Information on the effects of butadiene on reproductive organs is available from NTP and IISRP toxicity and carcinogenicity studies (Maronpot, 1987). In one NTP study, ovarian atrophy, hyperplasia and neoplasia in female mice and testicular atrophy in male mice were reported following exposure to 625 or 1,250 ppm butadiene for 60-61 weeks (Huff et al., 1985). A NOAEL for these effects was not identified from this study.

In the second NTP bioassay, mice were exposed to 0, 6.25, 20, 62.5, 200 or 625 ppm butadiene 6 hours/day, 5 days/week for up to 2 years (NTP, 1993). Interim sacrifices of 10 animals per sex per group were performed at 9 and 15 months, except at 625 ppm, when the reduction in survival was such that 2-8 animals were examined. In females, a statistically significantly increased incidence of ovarian atrophy was seen at 200 and 625 ppm at the 9-month sacrifice and at 62.5 ppm and above at the 15-month interim sacrifice. After 2 years, the incidence of ovarian atrophy showed a dose-related statistically significantly increase in all exposure groups, from 6.25 ppm upwards and it was reported that affected females had no evidence of oocytes, follicles or corpora lutea. After 2 years, the incidence of ovarian atrophy was 4/49 in controls compared with 19/49, 32/48, 42/50, 43/50 and 69/79 at 6.25, 20, 62.5, 200 and 625 ppm butadiene respectively. Uterine atrophy also occurred with increased incidence at 200 and 625 ppm, compared with controls, at 9 and 15 months and after 2 years of exposure. The incidence at 2 years was 1/50 in controls, compared with 8/50 and 41/78 at 200 and 625 ppm respectively. In males, there was an increased incidence of testicular atrophy at 625 ppm exposure groups at both the 9 and 15-month interim sacrifices and at 2 years. At 2 years the incidence was 53/72 compared with 1/50 in controls. In view of the reduction in survival in both sexes at 20 ppm and above and the severity of the neoplastic response in both sexes at 20 ppm and above and also in females at 6.25 ppm, it is possible that the gonadal effects seen in this study are a secondary consequence of severe generalised toxicity, rather than a direct effect of butadiene on the reproductive system. No significant ovarian effects were seen in females following either 15 days or 14 weeks of exposure to 625, 1,250, 2,500, 5,000 or 8,000 ppm butadiene (Maronpot, 1987).

Leydig cell tumours were observed in the IISRP bioassay in rats, at 1,000 and 8,000 ppm (Owen, 1981; Owen and Glaister, 1990; Owen et al., 1987).