1,2,3-trichloropropane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: - followed recognized toxicology testing procedures - GLP compliant - study results copied without further assessment from the SIDS dossier

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Reference 2

Reference Type:

secondary source

Title:

SIDS INITIAL ASSESSMENT REPORT For SIAM 18 - 1,2,3-Trichloropropane

Author:

OECD

Year:

2004

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

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: NAS Publication 1138 dtd 1977); Thompson-Weil Moving Average Method (1947)

GLP compliance:

yes

Test type:

standard acute method

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

Sex:

male/female

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: males weighing 205-275 grams; females weighing 180-240 grams when tested
- Fasting period before study: 16 - 24 h
- Housing: 1 per cage
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- no vehicle used


MAXIMUM DOSE VOLUME APPLIED: 1.8 ml/kg


DOSAGE PREPARATION (if unusual): no dosage preparation, treatment with undiluted test item via gavage

Doses:

Seven dose levels: 0.056, 0.1, 0.18, 0.32, 0.56, 1.0, and 1.8 ml/kg (equivalent to: 78.8, 140, 253, 450, 788, 1400 and 2530 mg/kg);

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: pre and post dosing and weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: not reported

Statistics:

Values determined by method of Thompson and Weil, where appropriate, or by Litchield and Wilcoxon and 95% confidence limits provided.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

120 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

188 mg/kg bw

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

152 mg/kg bw

Mortality:

males are generally more susceptible to 1,2,3-trichloropropane toxicity than females, see table 1 for details

Clinical signs:

other: The most prevalent in-life observations included: piloerection, polyuria, diarrhea, lacrimation, salivation, decreased activity, constricted pupils, corneal opacity, ptosis, nasal discharge, ataxia, lethargy, and difficult and labored breathing.

Gross pathology:

Significant gross necropsy findings included: discoloration of the stomach/intestines/urinary bladder/ liver and kidneys; testes drawn into abdominal cavity; distended cecum, prolapsed penis, black patches on liver, red patches on cardiac region and pyloric regions of stomach

Any other information on results incl. tables

- Table 1: Number of animals dead

 

Dose (mL/kg bw)	Mortality (# dead/total)			Time range of deaths (hours)
	Male	Female	Combined
Control	-	-	-
0.056	0/5	0/5	0/10
0.100	4/5	1/5	5/10	d 1 to d 10
0.180	5/5	-	-	d 1 to d 2
0.320	5/5	-	-	d 1 to d 2
0.560	5/5	5/5	10/10	d 1 to d 2
1.00	5/5	5/5	10/10	d 1
1.80	5/5	-	-	d 1

- Table 2: Average body weights and body weight gains before and after single oral treatment

Dose rate (ppm)	Body Weights (g)				Total Weight Gain
	day ‑1	day 1	day7	Day 14	g	% of lowest dose
Male
0.056	280 ± 16.6	257 ± 16.0	302 ± 25.4	328 ± 32.7	48 ± 21.7	100
0.100	261 ± 18.5	240 ± 20.9	200 ± 77.8	295	n/a	-
0.180	254 ± 17.1	231 ± 13.9	-	-	-	-
0.320	255 ± 15.0	237 ± 14.4	-	-	-	-
0.560	253 ± 14.8	229 ± 13.4	-	-	-	-
1.00	249 ± 9.6	228 ± 7.6	-	-	-	-
1.80	252 ± 21.7	249 ± 45.7	-	-	-	-
Female
0.056	226 ± 12.4	209 ± 13.9	231 ± 201	247 ± 18.2	21 ± 7.4	100
0.100	215 ± 11.7	193 ± 9.1	211 ± 9.5	230 ± 16.6	15 ± 22.6	71.4
0.560	215 ± 25	196 ± 24.3	-	-	-	-
1.00	216 ± 8.2	200 ± 7.1	-	-	-	-

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute oral toxicity of 1,2,3-trichloropropane was tested using a recognized scientific procedure and followed recognized GLP procedures.
The following threshold values were determined:
LD50 (oral, rat, male) = 120 mg/Kg bw
LD50 (oral, rat, female) = 188 mg/Kg bw
LD50 (oral, rat, combined) = 152 mg/Kg bw

Executive summary:

In the present study (Shell Development Company,1980) male and female Sprague-Dawley rats were treated once orally with undiluted 1,2,3 -trichloropropane via gavage and analysed for mortality, body weight development and clinical signs following generally the OECD TG 401 in compliance with GLP.

The following threshold values were determined:

LD50 (oral, rat, male) = 120 mg/Kg bw

LD50 (oral, rat, female) = 188 mg/Kg bw

LD50 (oral, rat, combined) = 152 mg/Kg bw

Based on this results 1,2,3 -trichloropropane is classified as Category III (Toxic if swallowed (oral)) according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

Thirty-five male and 35 female Sprague-Dawley rats were divided equally into 7 dosage groups (0.056, 0.1, 0.18, 0.32, 0.56, 1.0, and 1.8 ml/kg,equivalent to: 78.8, 140, 253, 450, 788, 1400 and 2530 mg/kg) and administered a single dose of the test material via gavage. Animals were fasted overnight for 16-24 hours (except for water). Animals observed for 14 days for mortality, pharmacologic and/or toxicologic effects hourly for the first 6 hours and at least twice daily for 14 days. Individual body weights were recorded prior to fasting, at time of dosing and on day 7 and 14, or at time of discovery of death. All animals were subjected to gross necropsy, either at termination or time of discovery of death.

The most prevalent in-life observations included: piloerection, polyuria, diarrhea, lacrimation, salivation, decreased activity, constricted pupils, corneal opacity, ptosis, nasal discharge, ataxia, lethargy, and difficult and labored breathing. Significant gross necropsy findings included: discoloration of the stomach/intestines/urinary bladder/ liver and kidneys; testes drawn into abdominal cavity; distended cecum, prolapsed penis, black patches on liver, red patches on cardiac region and pyloric regions of stomach.