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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: - review article on 19 different substances lacking individual animal data and giving only limited information on methodological details + limited information from the SIDS report study summary - original study report not available

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Testing of selected workplace chemicals for teratogenic potential.
Author:
Hardin BD, Bond GP, Sikov MR, Andrew FD, Beliles RP, Niemeier RW.
Year:
1981
Bibliographic source:
Scand J Work Environ Health. 1981;7 Suppl 4:66-75
Reference Type:
secondary source
Title:
SIDS INITIAL ASSESSMENT REPORT For SIAM 18 - 1,2,3-Trichloropropane
Author:
OECD
Bibliographic source:
Published OECD SIDS initial assessments of HPV chemicals: http://www.oecd.org/document/63/0,3343,en_2649_34379_1897983_1_1_1_1,00.html
Reference Type:
study report
Title:
Unnamed
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
- generally equivalent to OECD TG 414 but only 1 concentration tested
- pregnant Sprague Dawley rats were treated with a previously determined MTD of 80 mg/Kg bw 3-chloropropene from gestation day 1 to 15 via i.p. injection.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,2,3-Trichloropropane
- no further details reported

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: not reported
- Age at study initiation: not reported
- Weight at study initiation: 250 - 300 g
- no further details reported

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
corn oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: no data


VEHICLE
- Justification for use and choice of vehicle (if other than water): no justification given, but corn oil is the standard vehicle for volatile organic solvents
- no further details given
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
not applicable
Details on mating procedure:
- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/1
- Length of cohabitation: not detailed
- Proof of pregnancy: sperm in vaginal smear day 1 of pregnancy

Duration of treatment / exposure:
gd 1 - 15
Frequency of treatment:
daily
Duration of test:
until gd 21
Doses / concentrations
Remarks:
Doses / Concentrations:
37 mg/Kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
10 - 15
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: MTD based on a dose finding study with non-pregnant rats (MTD: dose without mortality, no marked signs of toxicity and less than 10 % reduction of bw gain within 2 weeks after last treatment
- Rationale for animal assignment (if not random): not reported

Examinations

Maternal examinations:
- sacrifice on gd 21 of gestation and gross necroscopy of dams and weighing and preservation (10 % formalin) of the brain, heart, lungs, liver, spleen, kidneys, adrenals, and ovaries for histopathological examination.
Ovaries and uterine content:
- examination of uterine content
Fetal examinations:
- weighing of fetuses, measurement of crownrump length, sex determination and examination for externally visible malformations.
- internal examination of 50 - 66 % of each litter (preserved in Bouin's fluid)
- preservation of the rest of the litter in ethanol for clearing and skeletal staining with alizarin red.
Statistics:
not reported
Indices:
not reported
Historical control data:
not reported

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
maternal effects only reported in a summary:
at least organ weights of 2 organs affected

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Basis for effect level:
other: maternal toxicity
Remarks on result:
not determinable
Remarks:
no NOAEL identified
Dose descriptor:
LOAEL
Effect level:
37 mg/kg bw/day
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
37 mg/kg bw/day
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
1,2,3-trichloropropane was tested for developmental toxicity in a study generally compliant to OECD 414. Pregnant Sprague Dawley rats were treated with a previously determined MTD of 37 mg/Kg bw from gestation day 1 to 15 via i.p. injection.
Maternal toxicity was found at the only tested dose but no signs of fetal toxicity or teratogenicity. Therefore a NOAEL of 37 mg/Kg bw can be derived for developmental toxicity, though the reliability of the study is limited due to the design of the study a screening test.
Executive summary:

In the present study (Hardin 1981) 1,2,3-trichloropropane was tested for developmental toxicity in a general compliance to OECD 414. Pregnant Sprague Dawley rats were treated with a previously determined MTD of 37 mg/Kg bw from gestation day 1 to 15 via i.p. injection. At gestation day 21 they were sacrificed and a full teratology examination was performed.

Maternal toxicity was found at the only tested dose but no signs of fetal toxicity or teratogenicity. Therefore a NOAEL of 37 mg/Kg bw can be derived for developmental toxicity, though the reliability of the study is limited due to the design of the study a screening test (only one dose was tested and as individual animal data and methodological details are not reported).