Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Only limited documentation is available. Read-across.

Data source

Reference
Reference Type:
publication
Title:
Oral Toxicity Study of 1,2,2-Trichloro-1,1,2-trifluoroethane
Author:
Michaelson JB, Huntsman DJ
Year:
1963
Bibliographic source:
J Med Chem. 1964, 7:378-9; PMID: 14204991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
at higher doses, application was scheduled at 3 h intervals
Principles of method if other than guideline:
At higher dose levels, the test item was administered in more than one dose. Such dosages were scheduled at 3 h intervals over a period of up to 12 h.
GLP compliance:
no
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): 1,2,2-trichloro-1,1,2-trifluoroethane
- Molecular formula: C2Cl3F3 (identical to submission substance)
- Molecular weight: 187.376 g/mol (identical to submission substance)
- Smiles notation: ClC(F)(F)C(Cl)(Cl)F (different from submission substance)
- InChl: InChI=1S/C2Cl3F3/c3-1(4,6)2(5,7)8 (different from submission substance)
- Structural formula: see attachment CAS_76-13-1_Structure.png (under "Illustration (picture/graph)")
- Physical state: liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Housing: individually
- Weight at study initiation: 200-300 g
- Fasting period before study: 12 h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED
Maximum 4 mL were applied per animal and time. For higher doses, the dose was administered in 3 h intervals.
Doses:
30, 35, 40, 45, 50, 55 g/kg bw (i.e. 30000, 35000, 40000, 45000, 50000 and 55000 mg/kg bw)

Remark of the registrant: Table I of the publication has "mg/kg" as unit for the dose in the column header together with the values 30, 35, 40, 45, 50 and 55 in the corresponding rows. The publication text describes the administered volumes of the undiluted liquid (density ca. 1.6 g/mL) and the body weights of the rats and gives explicitly the value for LD50. From this it can be concluded without any doubt that the unit cannot be "mg/kg" together with the given dose values. Thus the dose unit in the column header should read as "g/kg". All data in this endpoint study record are based on the dose levels given above.
No. of animals per sex per dose:
5 male rats were treated per dose group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
43 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths were observed up to a concentration of 40 g/kg bw. In the 45 and 50 g/kg bw groups 3 and 4 of 5 animals died, respectively. At a concentration of 55 g/kg bw all animals died (Table 1).
Animals at the lower levels of concentration died sooner than those at a higher concentration.
Clinical signs:
After administration all animals showed signs of lethargy, ruffled fur, and facial edema. The abdominal area was distended in all dose groups. Liquid fecal discharge was observed in all animals. These conditions persisted for 24 h. Complete reversion was observed within 48 h except for the ruffled fur which persisted until study completion.
Body weight:
All animals which died during the experiment lost weight. All animals surviving gained weight.
Gross pathology:
All animals exhibited consisted gross pathological changes comprising hemorrhage in the lungs, and abnormal distention of stomach and gastrointestinal tract with gas and fluid. Livers showed a mottled surface with normal color.
All other tissues examined appeared normal.

Any other information on results incl. tables

Table 1: Results of an oral toxicity study with 1,1,2-trichloro-1,2,2-trifluoroethane on rats

Group

Dose [g/kg bw]

Mortality

Approx. time of death

Average weight change [g]

deaths

survivors

1

30

0/5

 

+46

2

35

0/5

 

+41

3

40

0/5

 

+19

4

45

3/5

5-24 h

-12

+25

5

50

4/5

1-7 d

-49

+31

6

55

5/5

3-9 d

0

 

Remark of the registrant: Table I of the publication has "mg/kg" as unit for the dose in the column header together with the values 30, 35, 40, 45, 50 and 55 in the corresponding rows. The publication text describes the administered volumes of the undiluted liquid (density ca. 1.6 g/mL) and the body weights of the rats and gives explicitly the value for LD50. From this it can be concluded without any doubt that the unit cannot be "mg/kg" together with the given dose values. Thus the dose unit in the column header should read as "g/kg". The table above reflects this correction.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Acute oral toxicity of 1,1,2-trichloro-1,2,2-trifluoroethan was assessed in an oral toxicity study on Sprague-Dawley rats. No deaths were observed up to a concentration of 40 g/kg bw. In the 45 and 50 g/kg bw groups 3 and 4 animals died, respectively. At a concentration of 55 g/kg bw all five animals were found dead. Clinical signs included lethargy, ruffled fur, facial edema, distention of abdominal area, and liquid fecal discharge. These conditions persisted for 24 h. Necropsy revealed hemorrhage in the lungs and abnormal distention of stomach and gastrointestinal tract with gas and fluid. Livers showed a mottled surface with normal color. The calculated LD50 (oral, rat) of 1,1,2-trichloro-1,2,2-trifluoroethan is 43 g/kg bw.

The acute oral toxicity of the target chemical 1,1,1-trichloro-2,2,2-trifluoroethane is determined by read-across from an in vivo test (rats) with the source chemical 1,1,2-trichloro-1,2,2-trifluoroethane. The analogue approach is justified in Section 13 (Assessment Reports_Read-Across, in attachment CAS_354-58-5_Read-Across.pdf). As a consequence the value for LD50 (oral, rats) of 1,1,1-trichloro-2,2,2-trifluoroethane is 43 g/kg bw.
Executive summary:

Acute oral toxicity of 1,1,2-trichloro-1,2,2-trifluoroethan was assessed in an oral toxicity study on Sprague-Dawley rats. No deaths were observed up to a concentration of 40 g/kg bw. In the 45 and 50 g/kg bw groups 3 and 4 animals died, respectively. At a concentration of 55 g/kg bw all five animals were found dead. Clinical signs included lethargy, ruffled fur, facial edema, distention of abdominal area, and liquid fecal discharge. These conditions persisted for 24 h. Necropsy revealed hemorrhage in the lungs and abnormal distention of stomach and gastrointestinal tract with gas and fluid. Livers showed a mottled surface with normal color. The calculated LD50 (oral, rat) of 1,1,2-trichloro-1,2,2-trifluoroethan is 43 g/kg bw.

The acute oral toxicity of the target chemical 1,1,1-trichloro-2,2,2-trifluoroethane is determined by read-across from an in vivo test (rats) with the source chemical 1,1,2-trichloro-1,2,2-trifluoroethane. The analogue approach is justified in Section 13 (Assessment Reports_Read-Across, in attachment CAS_354-58-5_Read-Across.pdf). As a consequence the value for LD50 (oral, rats) of 1,1,1-trichloro-2,2,2-trifluoroethane is 43 g/kg bw.