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Toxicological information

Acute Toxicity: oral

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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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980
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:
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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,2,3-Trichloropropane
- Substance type: short-chain chlorinated hydrocarbon
- Physical state: clear colorless liquid
- Analytical purity: 98.25%
- Impurities (identity and concentrations): light ends of 0.66% and heavy ends 1.09%
- Composition of test material, percentage of components: not reported in SIDS dossier
- Purity test date: not reported in SIDS dossier
- Lot/batch No.: not reported in SIDS dossier
- Expiration date of the lot/batch: not reported in SIDS dossier
- Stability under test conditions: not reported in SIDS dossier
- Storage condition of test material: not reported in SIDS dossier

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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 levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
120 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
188 mg/kg bw
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:
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.
Body weight:
a dose dependent decrease of body weight gain or even a reduction of body weight was seen in the treated animals
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
Remarks:
Migrated information
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.