Registration Dossier

Toxicological information

Repeated dose toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26-11-1979 to 21-12-1979
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The purpose of the study was to observe the effects of 2,3-dichloro-1,3-butadiene (DCBD) on male rats after repeated inhalation exposure. An earlier acute study has shown the 4-hour LC50 of DCBD to be 2.08 mg/L. Based on these results concentrations for this study were set at 0 and 0.4 mg/L.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Analytical purity: 99% with 400 ppm phenothiazine added as a stabiliser.

Test animals

Species:
rat
Strain:
other: Crl:CD
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: Ten experimental rats: between 250 and 287 g, 10 control rats: between 246 and 285 g.
- Housing: Male albino rats were housed in pairs in 8' x 8' x 14' stainless steel cages.
- Diet: ad libitum, Purina certified rodent chow.
- Water: ad libitum.
- Acclimation period: 1 week prior to the test.

Administration / exposure

Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
other: DCBD vapours generated by passing nitrogen through a midget impinger containing DCBD
Remarks on MMAD:
MMAD / GSD: Not applicable for volatile gas
Details on inhalation exposure:
DCBD vapours generated by passing nitrogen through a midget impinger containing DCBD. The impinger was suspended in an ethylene glycol bath maintained at 0 °C by an Endocal refrigeration unit. Vapours were diluted with houseline air and carried to a 20 L glass exposure chamber via Teflon tubing.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
DCBD vapours were analysed on a Hewlett Packard 5710 Gas Chromatograph with a flame ionisation detector. The column used was a 1/4' x 5' stainless steel coil packed with a mixture of 3% 0V-17 on 80/100 Supelcoport and 5% 0V-7 on 100/120 Chromosorb G-HP. The column oven was operated at 110 °C. Gas standards were prepared daily by injecting measured amounts of DCD into evacuated glass bottles. After evaporation, DCBD vapours were mixed with room air by venting the bottles. Standard and chamber samples were injected into the G.C. by gastight syringe. Chamber samples were collected every half hour and atmospheric concentrations were calculated from the standard curve. Chamber temperature was monitored with a thermometer to assure a temperature = 27 °C. Chamber oxygen was monitored with a Biomarine Oxygen analyser to assure an atmosphere = 19%.
Duration of treatment / exposure:
10 rats were exposed to DCD 6 hours/day, 5 days/week for 2 weeks (10 exposures in total).
Frequency of treatment:
10 rats were exposed to DCD 6 hours/day, 5 days/week for 2 weeks.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.0 mg/L
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
0.40 mg/L
Basis:
analytical conc.
No. of animals per sex per dose:
10 male rats were included in this study.
Control animals:
yes, concurrent no treatment
Details on study design:
The purpose of the study was to observe the effects of 2,3-dichloro-1,3-butadiene (DCBD) on male rats after repeated inhalation exposure. The 4-hour LC50 of DCBD was found to be 2.08 mg/L. Based on this, design concentrations for this study were set at 0 and 0.4 mg/L. Ten rats were exposed to DCBD 6 hours/day, 5 days/week for 2 weeks, and ten control rats were simultaneously exposed to air only.
Positive control:
Not included in this study.

Examinations

Observations and examinations performed and frequency:
All rats were weighed and observed daily (except weekends) through the exposure period and for 14 days post-exposure.
Sacrifice and pathology:
After the 10th exposure, 5 rats were selected and sacrificed for gross and histopathological examination. The remaining rats were sacrificed on the 14th day of recovery for similar examination.
Other examinations:
Organ weights and organ to body weight ratios were determined for the heart, liver, lungs, kidney, spleen, testes and thymus.
Statistics:
Not included in this study.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL OBSERVATIONS: There were no notable differences between test and control rats in relation to clinical response to exposure.

BODY AND ORGAN WEIGHT ANALYSIS: Rats exposed to 0.4 mg/L showed an initial body weight depression followed by weight gain similar to that of controls. The mean relative liver weight of test rats was significantly higher in comparison with controls after the 10th exposure but had reverted to normal after 14 days treatment-free. The mean absolute lung and kidney weights of test rats were significantly lower than those of controls after the 10th exposure which correlates with significantly lower body weights of test rats at that time. The only organ weight effect evident after 14 days recovery was the significantly higher mean relative testis weight of test rats in comparison with controls. In the absence of any microscopic changes, the relevance of this weight change is unclear.

PATHOLOGY: No treatment -related macroscopic changes were evident. Microscopically, in the liver there was a slight increase in mitotic figures in the midsonal lobules of the 5 test rats sacrificed after the 10th exposure. The significance of this change is not clear since no other related morphologic alterations were observed. This change was also reversible - not evident in rats terminated 14 days after the last exposure. All other pathologic findings were considered either spontaneous or the result of intercurrent disease.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Table 1 - Exposure Data

Exposure Number

DCBD Concentration (mg/L)

Mean

S.D.

Range

1

0.45

0.06

0.38-0.58

2

0.39

0.06

0.31-0.47

3

0.40

0.05

0.26-0.44

4

0.41

0.02

0.36-0.44

5

0.39

0.06

0.26-0.45

6

0.44

0.06

0.33-0.52

7

0.38

0.04

0.31-0.41

8

0.37

0.05

0.28-0.43

9

0.41

0.02

0.28-0.43

10

0.37

0.11

0.04-0.42

Overall

0.40

0.07

0.04-0.58

Applicant's summary and conclusion

Conclusions:
Ten male Crl:CD rates were exposed 6 hours/day, 5 days/week for 2 weeks to 0.40 mg/L of DCD in air. A control group was simultaneously exposed to air only. During exposure, clinical observations of test rats were indistinguishable from those of controls. Test rats had significantly lower body weights than controls during the exposure period but showed a normal rate of weight gain during the recovery period. Pathologic examination showed no compound-related microscopic changes in rats exposed to DCD. Microscopically, there was a slight increase in liver mitotic figures following the 10th exposure. This change was not observed following 14 days recovery. The significance of this change is not clear since no other morphologic alterations were observed. The mean relative liver weight of the test rats was significantly higher upon comparison with controls after the 10th exposure but was in the normal range after 14 days recovery. The mean relative testing weight of test rats was significantly higher than that of controls after 14 days recovery. In the absence of any microscopic changes, the relevance of this weight change is questionable.
Executive summary:

Ten male Crl:CD rates were exposed 6 hours/day, 5 days/week for 2 weeks to 0.40 mg/L of DCBD in air. A control group was simultaneously exposed to air only. During exposure, clinical observations of test rats were indistinguishable from those of controls. Test rats had significantly lower body weights than controls during the exposure period but showed a normal rate of weight gain during the recovery period. Pathologic examination showed no compound-related microscopic changes in rats exposed to DCD. Microscopically, there was a slight increase in liver mitotic figures following the 10th exposure. This change was not observed following 14 days recovery. The significance of this change is not clear since no other morphologic alterations were observed. The mean relative liver weight of the test rats was significantly higher upon comparison with controls after the 10th exposure but was in the normal range after 14 days recovery. The mean relative testing weight of test rats was significantly higher than that of controls after 14 days recovery. In the absence of any microscopic changes, the relevance of this weight change is questionable.