Registration Dossier

A reliable secondary source is reported as reference, which discusses the available literature data.
Basing on existing data, no acute toxicity by oral route, dermal route and inhalation is expected for 1,1,2,2 -tetrachloro-1,2 -difluoroethane.

Reference

Endpoint:

acute toxicity: oral

Type of information:

other: discussion based on literature data

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The source is considered reliable since reported information is based on a review of existing peer-reviewed scientific literature by committees of experts in public health and related sciences.

Principles of method if other than guideline:

discussion of literature data

GLP compliance:

not specified

Test type:

other: not documented

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 25 000 mg/kg bw

Remarks on result:

other: species: rat (Clayton et al., 1966)

Two further values are reported:

- LD50 (mouse) = 23.5 mg/kg bw (Paribok, 1957)

- LD50 (mouse) = 800 mg/kg bw (Izermov, 1972)

However, according to ACGIH, the reliability of these values is questionable based on analytical concern.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

1,1,2,2-tetrachloro-1,2-difluoroethane does not meet the Regulation (EC) No. 1272/2008 classification criteria for acute toxicity by oral route.

Executive summary:

The American Conference of Governmental Industrial Hygienists(ACGIH) is a professional association of industrial hygienists and practitioners of related professions. One of the goals of the association is to provide information and guideline on exposure limits of substances in order to advance worker protection.

ACGIH information is based on a review of existing peer-reviewed scientific literature by committees of experts in public health and related sciences.

The acute toxicity of 1,1,2,2-tetrachloro-1,2-difluoroethane by oral route was assessed by ACGIH and to this purpose data deriving from scientific literature were rewieved.

The following LD50 values derived under independent experimental studies are reported:

- LD50 (rat) > 25000 mg/kg bw

- LD50 (mouse) = 23,5 mg/kg bw

- LD50 (mouse) = 800 mg/kg bw

However, according to ACGIH, the reliability of the last two values is questionable based on analytical concern and therefore the values are here reported for informational purpose only. They will not take into account to define the potential hazard for human health for acute toxicity by oral route.

Thus, for ACGIH, the only reliable value is LD50 (rat) >25000 mg/kg bw.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

25 000 mg/kg bw

Quality of whole database:

The secondary source is considered reliable since the discussed information is based on a review of existing peer-reviewed scientific literature by committees of experts in public health and related sciences.

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

other: discussion based on literature data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The source is considered reliable since reported information is based on a review of existing peer-reviewed scientific literature by committees of experts in public health and related sciences.

Principles of method if other than guideline:

Discussion of literature data

GLP compliance:

not specified

Test type:

other: not documented

Sex:

not specified

Dose descriptor:

LCLo

Effect level:

15 000 ppm

Based on:

not specified

Exp. duration:

4 h

Remarks on result:

other: Species: rat. (Clayton, 1967)

Sex:

not specified

Dose descriptor:

other: lethality observed

Effect level:

5 000 ppm

Based on:

not specified

Exp. duration:

18 h

Remarks on result:

other: Species: rat. (Greenberg and Lester, 1950)

Sex:

not specified

Dose descriptor:

other: lethality observed

Effect level:

10 000 ppm

Based on:

not specified

Exp. duration:

18 h

Remarks on result:

other: Species: rat. (Greenberg and Lester, 1950)

Sex:

not specified

Dose descriptor:

LC50

Effect level:

15 000 ppm

Based on:

not specified

Exp. duration:

2 h

Remarks on result:

other: Species: mouse, (Izermov, 1982)

The 18 -hour exposure of rats at either 5000 and 10000 ppm was lethal with extensive hemorrhage in the lungs. (Greenberg and Lester, 1950)

1,1,2,2 -tetrachloro-1,2 - difluoroethane is capable of sensitizing the beagle heart to exogenous adrenalin at concentration of 1200 ppm (Clark and Tinston, 1973).

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

1,1,2,2-tetrachloro-1,2-difluoroethane does not meet the Regulation (EC) No. 1272/2008 classification criteria for acute toxicity by inhalation.

Executive summary:

The American Conference of Governmental Industrial Hygienists(ACGIH) is a professional association of industrial hygienists and practitioners of related professions. One of the goals of the association is to provide information and guideline on exposure limits of substances in order to advance worker protection.

ACGIH information is based on a review of existing peer-reviewed scientific literature by committees of experts in public health and related sciences.

The acute toxicity of 1,1,2,2-tetrachloro-1,2-difluoroethane by inhalation was assessed by ACGIH and to this purpose data deriving from scientific literature were rewieved.

The following data, derived under independent experimental studies, are reported:

- LCLo (4h, rat) = 15000 ppm (125 mg/l)

- LC50 (2h, mouse) = 15000 ppm (125 mg/l)

- Lethality observed (18h, rat) = 5000 ppm (41,7 mg/l) and 1000 ppm (83,4 mg/l). (The 18-hour exposure of rats, at either 5000 and 10000 ppm resulted in extensive hemorrhage in the lungs.)

- Furthermore, as reported by Clark and Tinston (1973), 1,1,2,2 -tetrachloro-1,2 - difluoroethane is capable of sensitizing the beagle heart to exogenous adrenalin at concentration of 1200 ppm (10 mg/l).

According to Regulation (EC) No. 1272/2008 the generic concentration limits to classified a substance for inhalation toxicity are based on 4 hour testing exposures. Furthermore, according to EU and OECD guidelines the rat is the preferred species to be tested under acute toxicity studies. For vapours, the concentration limit of LC50 = 20 mg/l is the value to classified a substance as hazardous.

Since under the 4-hour exposure study on rats the lowest concentration at which lethality was observed is 125 mg/l (15000 ppm), the classification criteria for acute toxicity by inhalation route according to Annex 1 of Regulation (EC) No. 1272/2008 are not fulfilled. Furthermore, other data confirms as no acute toxicity is expected, since the reported cooncentrations at which lethality was observed are above the generic concentration limits to classified the substance as toxic, even for time of exposure well-longer.

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating conc.

Value:

125 049 mg/m³ air

Quality of whole database:

The secondary source is considered reliable since the discussed information is based on a review of existing peer-reviewed scientific literature by committees of experts in public health and related sciences.

Reference

Endpoint:

acute toxicity: dermal

Type of information:

other: discussion based on literature data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The source is considered reliable since reported information is based on a review of existing peer-reviewed scientific literature by committees of experts in public health and related sciences.

Principles of method if other than guideline:

Discussion of literature data

GLP compliance:

not specified

Test type:

other: not documented

Sex:

not specified

Dose descriptor:

discriminating dose

Effect level:

> 7 500 mg/kg bw

Based on:

not specified

Remarks on result:

other: species. rabbit. (Clayton et al., 1966

According to the reference, no deaths were seen in rabbits following a dermal application of 7500 mg/kg bw to the skin.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

1,1,2,2-tetrachloro-1,2-difluoroethane does not meet the Regulation (EC) No. 1272/2008 classification criteria for acute toxicity by dermal route.

Executive summary:

The American Conference of Governmental Industrial Hygienists(ACGIH) is a professional association of industrial hygienists and practitioners of related professions. One of the goals of the association is to provide information and guideline on exposure limits of substances in order to advance worker protection.

ACGIH information is based on a review of existing peer-reviewed scientific literature by committees of experts in public health and related sciences.

The acute toxicity of 1,1,2,2-tetrachloro-1,2-difluoroethane by dermal route was assessed by ACGHI and to this purpose data deriving from scientific literature were rewieved.

No deaths were seen in rabbits following dermal application of 7500 mg/kg to the skin.

According to Regulation (EC) No. 1272/2008 the generic dose limit to classified a substance for dermal toxicity is LD50 = 2000 mg/kg.

Althougt the dose limit is based on the rat as preferred species to be tested under acute toxicity studies, the dose at which no deaths were seen in rabbit is well above the dose limit of 2000 mg/kg bw.

It can be concluded that no acute toxicity by dermal route is expected for 1,1,2,2-tetrachloro-1,2-difluoroethane, and therefore no classification is required according to Regulation (EC) No. 1272/2008.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

7 500 mg/kg bw

Quality of whole database:

The secondary source is considered reliable since the reported information is based on a review of existing peer-reviewed scientific literature by committees of experts in public health and related sciences.

Reported data derive from the ACGIH sheet for the substance 1,1,2,2 -tetrachloro-1,2 -difluoroethane.

The American Conference of Governmental Industrial Hygienists(ACGIH) is a professional association of industrial hygienists and practitioners of related professions. One of the goals of the association is to provide information and guideline on exposure limits of substances in order to advance worker protection, and to this purpose the available scientific data on target substances are revised.

ACGIH summaries are based on a review of existing peer-reviewed scientific literature by committees of experts in public health and related sciences, therefore ACGIH is considered a reliable secondary source of information.

For the acute toxicity by oral route, the reported key value from ACGIH is LD50 (rat) >25000 mg/kg bw.This value derives from the acute toxicity study on rats (Clayton, 1966) where the approximate lethal dose > 25000 mg/kg bw was observed.

The values of LD50 (mouse) = 23.5 mg/kg bwandLD50 (mouse) = 800 mg/kg bw are also reported by ACGIH, however,according to the source,their reliability is questionable based on analytical concern.

Furthermore, the value of LD > 25000 mg/kg bw is consistent with the doses tested under two independent repeated dose toxicity studies on rats, in which 2000 mg/kg bw were administered for 33 days and 5000 mg/kg bw were administered for 10 days.

For acute toxicity by dermal route, the result of a study on rabbit is reported. No deaths were seen following dermal application of 7500 mg/kg to the skin.

For the acute toxicity by inhalation,the following data, derived under independent experimental studies, are quoted:

- LCLo (4h, rat) = 125049 mg/m3 (15000 ppm)

- LC50 (2h, mouse) = 125049 mg/m3 (15000 ppm)

- Lethality observed (18h, rat) = 41683 mg/m3 (5000 ppm) and 83366 mg/m3 (10000 ppm).

Furthermore, the 18-hour exposure of rats, at either 5000 and 10000 ppm resulted in extensive hemorrhage in the lungs.

As discussed by Clark and Tinston (1973), 1,1,2,2 -tetrachloro-1,2 - difluoroethane is capable of sensitizing the beagle heart to exogenous adrenalin at concentration of 1200 ppm.

Basing on exisiting data, for all the exposure routes, the doses/concentration of effect are well-above the European generic limits to classified the substance as hazardous for acute toxicity. In conclusion, no acute toxicity by oral route, dermal route and inhalation is expected for 1,1,2,2-tetrachloro-1,2-difluoroethane.

Justification for selection of acute toxicity – oral endpoint
The reported reference is a secondary source which discusses the available literature data.
Among the discussed data, the reported value of LD (rat) > 25000 mg/kg bw is considered the more reliable.

Justification for selection of acute toxicity – inhalation endpoint
The reported reference is a secondary source which discusses the available literature data.
According to Regulation (EC) No. 1272/2008 the generic concentration limits to classified a substance for inhalation toxicity are based on 4 hour testing exposures. Furthermore, according to EU and OECD guidelines the rat is the preferred species to be tested under acute toxicity studies.
Therefore, the reported value of LCLo (4h, rat) = 125 mg/l (15000 ppm) is the more representative of the hazard profile for acute inhalation toxicity of the substance.

Justification for selection of acute toxicity – dermal endpoint
The reported reference is a secondary source which discusses the available literature data.
Only the reported value for acute dermal toxicity exists: LD0 (rabbit) >= 7500 mg/kg bw.

Basing on exisiting data, for all the exposure routes, the doses/concentration of effect are well-above the European generic limits to classified the substance as hazardous for acute toxicity. In conclusion, no acute toxicity by oral route, dermal route and inhalation is expected for 1,1,2,2-tetrachloro-1,2-difluoroethane.

According to Regulation (EC) No. 1272/2008, 1,1,2,2 -tetrachloro-1,2 -difluoroethane does not meet the classification criteria for Acute Toxicity.