Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with restrictions

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Assessment of teratogenic potential of 1,2,3-, 1,2,4- and 1,2,5-trichlorobenzenes in rats.
Author:
Black WD et al
Year:
1988
Bibliographic source:
Bull. Environ. contam. Toxicol 41, 719-726
Reference Type:
publication
Title:
Evaluation of risks to health from environmental exposure in Canada
Author:
Giddings M
Year:
1994
Bibliographic source:
Carcino.Ecotox. Revs. C12, 517-525
Reference Type:
publication
Title:
A teratological evaluation following oral administration of trichloro- and dichlorobenzene to the rat.
Author:
Ruddick VK et al
Year:
1983
Bibliographic source:
Teratology 27, 73A-74A

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
Housing and feeding conditions not reported; exposure too short; number of animals exposed too small; weight of dams recorded only at 22nd day of gestation; food consumption, number of corpora lutea, sex of each foetus not recorded
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,2,3-trichlorobenzene
- Analytical purity: 99.5%

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration of treatment / exposure:
day 6 - day 15 of gestation
Frequency of treatment:
once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 150, 300, 600 mg/kg bw/day in corn oil
Basis:
actual ingested
No. of animals per sex per dose:
Each groups consisted of approximately 13-14 dams

Control animals:
yes, concurrent vehicle
Details on study design:
Sex: female
Duration of test: until day 22

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
ca. 150 mg/kg bw/day
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
ca. 600 mg/kg bw/day
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables


--None of the animals displayed any signs of toxicity, 
--Body weight development was not affected.
--Mortality
300 mg-group: 1 dam died
control group: 1 dam died

--Fetal data
no difference to the concurrent control in
number of dams at term, nimber of dams inseminated, resorptions, dead  fetuses, fetal weights, litter size
no viseral or skeletal abnormalities
- Skeletal deviations 
(number of pups affected/number of litters affected 150 mg-gr., 300  mg-gr., 600 mg-gr versus control): 
Sternal anomalies: 1/1, 1/1, 13/3 versus 1/1
wavy ribs: 0, 1/1, 1/1 versus 1/1
14th rib: 1/1, 0, 0 versus 0
13th rib(short): 1/1, 0, 0 versus 0

----Maternal data (significant changes):
--increase in relative liver weight: 
600 mg-gr: 5.8 % versus 5.1% of control
--increase in ADPM activity:
600 mg-gr: 27.3 nanomoles formaldehyde/hr/mg protein versus 
22.8 nanomoles formaledhyde/hr/mg protein of control
--decrease in hemoglobin concentration:
500mg-gr, 300 mg-gr: 11.3g/dl, 11.3g/dl versus 12.0g/dl of control
--decrease in hematocrit levels:
600 mg-gr: 31.1% versus 33.3% of controls
--histopathology.
-thyroid, 300 mg-gr and 600 mg-gr: reduction in follicle size accompanied  by agular collapse; 600 mg-gr:increased epithelial height accompanied by  cytoplasmatic vacuolation
-liver, 300 mg-gr, 600 mg-gr: mild increased periportal cytoplasmic  eosinophilia and mild anisokaryosis of hepatocellular nuclei
-spleen
mild increased hematopoiesis in some females (no further information)
--TRCB residues:
only found in traces in the perirenal fat of the 300 mg-gr. and 600 mg-gr  consistting of 0.02 and 0.4 ppm, respectively

Applicant's summary and conclusion