2,3,4-trichlorobut-1-ene

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report meeting basic scientific principles

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1976

Reference 2

Reference Type:

secondary source

Title:

No information

Author:

OECD

Year:

1993

Bibliographic source:

OECD/SIDS. Screening Information Data Set (SIDS) of OECD High Production Volume Chemicals Programme, 17, (1993)

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

yes

Remarks:

, lack of historical control data

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,3,4-trichlorobut-1-ene

EC Number:

219-397-9

EC Name:

2,3,4-trichlorobut-1-ene

Cas Number:

2431-50-7

Molecular formula:

C4H5Cl3

IUPAC Name:

2,3,4-trichlorobut-1-ene

Details on test material:

- Name of test material (as cited in study report): 2,3,4-trichlorobutene-1 (TCB)
- Analytical purity: checked by GC
- Stability under test conditions: freshly purified and weekly received
- Other: Source: Bayer AG, Dormagen, Germany
- Storage condition of test material: at room temperature

Test animals

Species:

rat

Strain:

other: Wistar derived albino rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Central Institute for the Breeding of Laboratory Animals TNO, Zeist, The Netherlands.
- Age at study initiation: 4 weeks
- Weight at study initiation: 65 g for males, 71 g for females
- Fasting period before study:
- Housing: 5 per cage, individually during exposure in wire screen cages wihtin an inhalation chamber.
- Diet (e.g. ad libitum): stock diet
- Water (e.g. ad libitum):tap water
- Acclimation period: no data

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: nitrogen flow mixed with air

Remarks on MMAD:

MMAD / GSD: not applicable

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 2.5 m3 stainless steel/glass inhalation chamber
- Method of holding animals in test chamber: all rats were housed individually in wire screen cages within an inhalation chamber
- System of generating particulates/aerosols: Suitable quantities of the test material were put into fritted glass bubble evaporators (kept at room temperature) through which a measured, dried and filtered nitrogen flow was passed. Each of the TCB/nitrogen mixtures thus produced, were fed into the inlet piece of the inhalation chamber, where it was mixed with a carrier air flow of 20m3/h. Teflon and stainless steel transport tubes were used.
- Temperature, humidity, pressure in air chamber: 22 ºC, 50-60 %
- Air flow rate: 20m3/h

TEST ATMOSPHERE
- Brief description of analytical method used: GC, Intersmat 120 DFL gaschromatograph
- Samples taken from breathing zone: yes

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

During the exposures 3-4 air samples/hour were taken from each of the inhalation chambers by a timer controlled sampling valve.
The samples were analyzed by GC.

Duration of treatment / exposure:

28 days

Frequency of treatment:

6h/d, 5d/w

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.004, 0.013, 0.054, 0.103 mg/L (0, 0.55, 2.0, 8.1, 15.5 ppm)
Basis:

No. of animals per sex per dose:

15

Control animals:

yes, sham-exposed

Details on study design:

- Post-exposure recovery period in satellite groups: 5 animals per sex and dose were observed for 2 weeks

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: 2 times a week

HAEMATOLOGY: Yes
- Time schedule for collection of blood: after 4 and six weeks
- How many animals: 15 per sex at week 4, 5 per sex at week 6
- Parameters: diff. blood cell count, Hb, Hct, MCV, MCH

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: after 4 and six weeks
- How many animals: 10 per sex at week 4, 5 per sex at week 6
- Parameters: Serum AP, LDH, GPT, GOT, blood urea nitrogen, GGT

URINALYSIS: Yes
- How many animals: 10 per sex at week 4, 5 per sex at week 6
- Parameters: Volume, creatinine, specific gravity, pH, sugar, protein, blood, urobilinogen, bilirubin, ketones and urine sediment analysis

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

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:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

effects observed, treatment-related

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Details on results:

No haematology, clinical biochemistry and organ weight data were collected from the highest dose group due to early mortality.

CLINICAL SIGNS AND MORTALITY
Mortality was increased at 8.1 ppm and was 100 % at the highest dose level of 15.5 ppm. Animals of these gorups showed nose and eye irritation, dyspnoe and temporary incontinence of faeces and urine. Rats of the 2.0 ppm group showed restlessness.

BODY WEIGHT AND WEIGHT GAIN
The body weight gain was reduced in animals of the 2.0, 8.1 and 15.5 ppm groups in a dose-related manner.
At 0.55 ppm the body weights were comparable with the control animals.

HAEMATOLOGY
Increased normochromatic erythrocytes and decreased numbers of lymphocytes were observed at 2.0 and 8.1 ppm.
A slight eosinophilia occured at 8.1 ppm.

CLINICAL CHEMISTRY
Serum AP enzyme activities were increased in males of the 8.1 and 2.0 ppm groups after 4 and 6 weeks.
Blood urea nitrogen levels were increased at 8.1 ppm after 4 weeks.

URINALYSIS
Decreased urine volumes were found in females of the 8.1 ppm group after 4 and 6 weeks.

ORGAN WEIGHTS
At 2.0 and 8.1 ppm increased relative weight of lungs were observed.
Relative liver weights were increased in females of the 8.1 ppm group.

GROSS PATHOLOGY
Lungs of the 15.5 ppm group appeared insufficiently collapsed and showed focal congestion and haemorrhages.
At 8.1 and 2.0 ppm lungs looked too spongy, and showed small haemorrhages and pneumonic areas.

HISTOPATHOLOGY: NON-NEOPLASTIC
At 2.0 and 8.1 ppm hyperplasia and degenerative metaplasia of the epithelium of lung, nose and bronchi were observed.
At 0.55 ppm slight hyper- and metaplasie of the lining epithelium was observed in the trachea and nasal cavity.

Effect levels

1

Dose descriptor:

NOAEC

Effect level:

< 0.55 ppm

Sex:

male/female

Basis for effect level:

other: 0.004 mg/L

2

Dose descriptor:

LOAEC

Effect level:

0.55 ppm

Sex:

male/female

Basis for effect level:

other: 0.004 mg/L hyper- and metaplasia of the lining epithelium in the trachea and nasal cavity

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

RS-Freetext:
15.5 ppm: mortality 100 %, nose and eye irritation,
dyspnoe, degenerative, hyperplastic and metaplastic
epithelial changes of respiratory tract
8.1 ppm: increased mortality, nose and eye irritation,
dyspnoe, growth retardation, haematological changes,
biochemical changes (alkaline phosphatase) in male,
decreased urine volume in female, increased rel. lung
weights, increased rel. liver weights in female,
degenerative, hyperplastic and metaplastic epithelial
changes of respiratory tract 2.0 ppm: restlessness, growth
retardation, haematological changes, biochemical changes
(alkaline phosphatase) in male, increased rel. lung weights,
degenerative, hyperplastic and metaplastic epithelial
changes of respiratory tract 0.55 ppm: slight hyper- and
metaplasia in trachea and nasal cavitiy

Applicant's summary and conclusion

Conclusions:

A NOAEC of 0.55 ppm for repeated inhalation exposure in rats could be established.
A LOAEC of 2.0 ppm was established based on increased relative lung weights and histopathologic changes of the respiratory epithelium.

Executive summary:

In a subacute inhalation toxicity study male and female Wistar derived albino rats were exposed to 0, 0.55, 2.0, 8.1 and 15.5 ppm 1-Butene, 2,3,4-trichloro for 6 hours a day, 5 days per week for 28 days. The exposure period was followed by 2 weeks observation time. Biochemistry, haematology and clinical pathology were assessed.

A NOAEC of 0.55 ppm could be established. At 2.0 and 8.1 ppm increased relative weight of lungs and hyperplasia and degenerative metaplasia of the epithelium of lung, nose and bronchi were observed. Mortality was increased at 8.1 ppm and was 100 % at the highest dose level of 15.5 ppm.