1,2,3-trichloropropane

Developmental toxicity / teratogenicity

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

Reference

Reference 1

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 2

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 3

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

Test material information

Constituent 1

Reference substance name:

1,2,3-trichloropropane

EC Number:

202-486-1

EC Name:

1,2,3-trichloropropane

Cas Number:

96-18-4

Molecular formula:

C3H5Cl3

IUPAC Name:

1,2,3-trichloropropane

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system 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

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)

1

Dose descriptor:

NOAEL

Basis for effect level:

other: maternal toxicity

Remarks on result:

not determinable

Remarks:

no NOAEL identified

2

Dose descriptor:

LOAEL

Effect level:

37 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

3

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).