2-vinylpyridine

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

other: OECD 408

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: While this study is not a reproductive toxicity screening study, observations of the reproductive organs in subchronic studies can be helpful in understanding target organ toxicity.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 408: 90-day repeated dose oral toxicity

Deviations:

yes

Remarks:

5 days/week rather than 7 days/week. This study precedes establishment of 408 Guideline

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-vinylpyridine

EC Number:

202-879-8

EC Name:

2-vinylpyridine

Cas Number:

100-69-6

Molecular formula:

C7H7N

IUPAC Name:

2-ethenylpyridine

Details on test material:

The material submitted had a 97% minimum purity, with inhibitor (tertiary butyl catechol) added 0.09-0.11% by weight. Material was distilled byt he Chemical Processing Engineering Laboratory, of Kodak Research Laboratories to remove impurities and stabilizer. Average purity of triplicate analysis was 97.34 ± 0.15% pure 2-VP.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The concentration of the test material in corn oil was assayed (UV/Vis spectroscopy) throughout the experimental period. 2-Vinylpyridine was determined to be stable for at least 11 days, as prepared and stored.

Duration of treatment / exposure:

92 days, 5 days per week excluding weekends.

Frequency of treatment:

5 days per week excluding weekends.

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 20, 60, 120 mg/kg body weight/day
Basis:
actual ingested

No. of animals per sex per dose:

30

Positive control:

none

Examinations

Parental animals: Observations and examinations:

Adult males and non-gravid females were examined for gross abnormalities and for histopathologic effects of treatment.

Postmortem examinations (parental animals):

Body weight, organ weights, gross and histopathological examination of organs.

Statistics:

All numerical data were evaluated using computerized tests as follows: One-way analysis of variance, Bartlett's test and Duncan's multiple range test. F-tests were performed where the Bartlett's test indicated a significant difference in variances which would interfere with interpretation of analytical results.

Reproductive indices:

Organ weight and histopathologic examination

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Food consumption and body weight gain was significantly decreased at 120 mg/kg bw/d.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Food consumption and body weight gain was significantly decreased at 120 mg/kg bw/d.

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

No histopathology

Details on results (P0)

Food consumption was significantly decreased in the high dose (120 mg/kg bw/day) males, correlated with decreased body weight and increased relative organ weights. Testes weight relative to body weight (but not absolute weight) was increased in high dose males, as were weights of liver, kidney, brain and adrenal gland. Relative ovary weight (but not absolute weight) was significantly increased in high dose females, along with weights of liver and kidney. No effects were noted in the mid-dose group of 60 mg/kg bw/d. No gross or microscopic lesions were found when histopathologic examination was undertaken.

Effect levels (P0)

1

Dose descriptor:

NOAEL

Effect level:

60 mg/kg bw/day (actual dose received)

Sex:

male

2

Dose descriptor:

NOAEL

Effect level:

ca. 60 mg/kg bw/day (actual dose received)

Sex:

female

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

If weight changes qualify as toxicity, the NOAEL for reproductive organ toxicity is 60 mg/kg bw/d. These, however, are considered minor in the absence of histopathology. The overall NOAEL for systemic effects in the 90-day study is 20 mg/kg bw/d.

Applicant's summary and conclusion

Conclusions:

In a subchronic study of 2VP, male and female Sprague Dawley rats were administered test material by oral gavage 5 days per week, for 92 weeks, at doses of 120, 60 and 30 mg/kg bw/day. Food and water consumption, weight gain and body weights were tracked, and gross and histopathologic examinations were undertaken after sacrifice at 92 days. Food consumption, weight gain and body weight were significantly decreased among high dose animals. Relative organ weight changes in testis and ovaries were observed in high dose animals. No histopathologic effects were noted upon examination. Relative organ weights can indicate sparing of these organs when body weight decreases due to stress or chemical exposure. The NOAEL for reproductive organ toxicity can conservatively be 60 mg/kg bw/d. The overall NOAEL for the 90-day study is 20 mg/kg bw/d. This indicates that 2VP does not specifically promote reproductive toxicity.