3,4-dichlorobut-1-ene

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Remarks:

combined repeated dose and reproduction / developmental screening

Type of information:

experimental study

Adequacy of study:

other information

Study period:

1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-guideline study. Adopted according to OECD SIDS (public available peer reviewed source). The original source is available and has been reviewed.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Toxicity testing reports of environmental chemicals

Author:

Ministry of Health & Welfare (Japan)

Year:

1996

Bibliographic source:

Vol. 4, chapter: 3,4-Dichloro-1-butene, pp. 529-533, ISSN 1340-3842

Reference 2

Reference Type:

secondary source

Title:

SIDS Initial Assessment Report for 11th SIAM

Author:

OECD SIDS

Year:

2003

Bibliographic source:

UNEP Publications

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,4-dichlorobut-1-ene

EC Number:

212-079-0

EC Name:

3,4-dichlorobut-1-ene

Cas Number:

760-23-6

Molecular formula:

C4H6Cl2

IUPAC Name:

3,4-dichlorobut-1-ene

Details on test material:

- Name of test material (as cited in study report): 3,4-Dichloro-1-butene
- Analytical purity: 99.7%

Test animals

Species:

rat

Strain:

other: Crj:CD (SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 9 weeks old for males, 8 weeks old for females
- Weight at study initiation: 343-384 g for males, 192-222 g for females

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

males: 44 days; females: from 14 days before mating to day 3 of lactation

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0.4, 2, 10 or 50 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Details on study design:

Post-exposure period: no data

Positive control:

No

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes
General condition was observed once a day.

BODY WEIGHT: Yes
- Time schedule for examinations: once a week.

HAEMATOLOGY: Yes
- Time schedule for collection of blood: for males was carried out only at time of necropsy after 44 days of chemical exposure.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: for males was carried out only at time of necropsy after 44 days of chemical exposure.

URINALYSIS: Yes
- Time schedule for collection of urine: Urinalysis was carried out 38 or 40 days (males)

Food/water consumption were determined once a week.

Sacrifice and pathology:

ORGANS EXAMINED AT NECROPSY:
-organ weight: brain, heart, liver, kidney, spleen, adrenal, thymus, testes, epididymis
-microscopic: all animals in control and 50 mg/kg, and males failed to cause pregnancy or non-pregnant females: brain, pituitary gland, eyeball, thyroid gland, parathyroid gland, thymus, heart, lung, liver, kidney, adrenal, spleen, stomach, small intestine, large intestine, pancreas, urinary bladder, bone marrow, testes, epididymis, prostate, seminal vesicle, ovary, uterus, vagina, mammary gland.

Statistics:

Performed but not reported in detail.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

1 female was dying 2 days after parturition.

Mortality:

mortality observed, treatment-related

Description (incidence):

1 female was dying 2 days after parturition.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Significant differences from controls were not observed

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

Description (incidence and severity):

increase in total protein

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

effects observed, treatment-related

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Male: increase in kidney weight at 10 mg/kg (absolute (p<0.05) and liver weight at 50 mg/kg (absolute (p<0.01) and relative (p<0.01)); female: increase in kidney weight at 50 mg/kg (p<0.01)).

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

Liver swelling (male: 2/10, female: 1/10) and kidney swelling (male: 3/10, female: 0/10) at 50 mg/kg.

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

male and female showed hepatocellular hypertrophy at 50 mg/kg

Histopathological findings: neoplastic:

no effects observed

Details on results:

Males: Ephemeral decreased locomotor activity (all rats, the first day of the study in the 50 mg/kg bw/day group, 1/10, day 5-12) and ephemeral slaver (50 mg/kg: 10/10, the first day of the study).
Females: Death(50 mg/kg: 1/10), ephemeral decreased locomotor activity (50 mg/kg: 10/10), and ephemeral slaver (50 mg/kg: 5/10, the first day of the study).
In males, absolute kidney weights were slightly increased with 10 mg/kg/day dose. Absolute and relative weights of the liver and kidneys were increased with 50 mg/kg/day dose. Blood chemical examination revealed an increase in total protein. The histopathological examination revealed increased hyaline droplets in the renal tubular epithelium with doses of 10 and 50 mg/kg/day and hepatocellular hypertrophy with dose of 50 mg/kg/day.
One female was sacrificed in a moribund condition on day 2 of lactation. An increase in relative kidney weights was observed at the dose of 50 mg/kg/day. However, no histopathological changes considered to be related to the change of the kidney weight were detected. Hepatocellular hypertrophy was observed at the dose of 50 mg/kg/day.
NOAELs in this repeat dose study are 2 mg/kg/day for males and 10 mg/kg/day for females, but the renal toxicity in males is considered to be male rat specific, probably due to alpha2U-globulin involvement. Therefore, the NOAEL for repeated dose toxicity is considered to be 10 mg/kg/day.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

2

Dose descriptor:

LOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Based on ephameral decreased locomotor activity, liver swelling, kidney swelling, liver weight, in male and female animals.

Target system / organ toxicity

Critical effects observed:

not specified