Dichloromethylbenzene

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Justification for dichloromethylbenzene in the TRGS 900

Data source

Reference

Reference Type:

other: justification for the OEL in the TRGS 900

Title:

Begründung zu Dichlormethylbenzol in TRGS 900

Author:

Anonymous

Year:

2016

Bibliographic source:

Ausschuss fuer Gefahrstoffe - AGS-Geschäftsführung- BAuA - www.baua.de-

Materials and methods

Type of study / information:

Scientific justification for a legally binding occupational threshold value in Germany.

Test guideline

Qualifier:

no guideline available

Guideline:

other: scientific expert panel

Principles of method if other than guideline:

Scientific justification for a legally binding occupational threshold value in Germany.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dichloromethylbenzene

EC Number:

249-854-8

EC Name:

Dichloromethylbenzene

Cas Number:

29797-40-8

Molecular formula:

C7H6Cl2

IUPAC Name:

(dichloromethyl)benzene

Details on test material:

not applicable

Results and discussion

Any other information on results incl. tables

Executive summary

TRGS 900 justification for a legally binding Workplace Exposure Limits in Germany of

8 mg/m³ (1.3 ml/m³); long term

16 mg/m³ (2.6 ml/m³); short term (long term value can be exceeded by a factor of 2)

The dichlorotoluene mixture shows only very low toxicity (oral, dermal, inhalation) after acute administration. It is light to moderately irritating to skin and eyes and has no sensitizing potential in animal experiments on guinea pigs.

In an inhalation hazard test in rats with a saturated vapour atmosphere, at 95°C death occurred after an exposure of 7 hours. The autopsy showed evidence of a slight damage to lungs and liver.

Regarding the question of the toxicity of the dichlorotoluene mixture after repeated application, the results of a subacute oral toxicity study in rats are available.

The NOAEL for males is 100 mg/kg bw/day; in higher doses males revealed a slight hypertrophy of the central lobular hepatocytes, and kidney changes as a result of hyaline droplet accumulation, which manifests itself already in the 20 mg/kg group and which is considered as a species- and gender-specific phenomenon.

In females the NOAEL in this study was 500 mg/kg bw/day.

In the Ames test the dichlorotoluene mixture as well as the pure 2,4-dichlorotoluene is not mutagenic, and in the micronucleus test in mice the dichlorotoluene mixture shows no clastogenic effect .

In the subacute study in rats, there was no evidence of relevant effects on toxicity to reproduction. The effects reported in a publication after oral treatment with 2,4-dichloro-toluene are not taken into account due to the lack of validity of the study.

For the derivation of a guidance value only the results of the subacute oral toxicity study in rats are used. The NOAEL for a human relevant effect is 100 mg/kg bw/day.

Starting from a NOAEL of 100 mg/kg and a total extrapolation factor of 84 results yields a dose of 1.2 mg/kg bw/d. For humans the expert committee derived for a dose of 1.2 mg/kg bw/d, a human body weight of 70 kg and a tidal volume of 10 m³ during 8 hours a Workplace Exposure Limit value of 8 mg/m³.

Accordingly, the Committee derived a Workplace Exposure Limit (ARW) of 1.3 ppm = 8 mg/m³ with a Category II short term limit (long term value can be exceeded by a factor of 2 leading to 16 mg/m³ (2.6 ml/m³); short term). This guidance level is considered as sufficient to ensure the protection of exposed persons to potential hepatotoxic effects of dichlorotoluene mixture.

Applicant's summary and conclusion

Conclusions:

TRGS 900 justification for a legally binding Workplace Exposure Limits in Germany of
8 mg/m³ (1.3 ml/m³); long term
16 mg/m³ (2.6 ml/m³); short term (long term value can be exceeded by a factor of 2)

Executive summary:

The available experimental toxicity data were evaluated by the Federal Institute for Occupational Safety and Health (BAuA) for the justification of a legally binding workplace exposure limit in Germany.

Executive summary

TRGS 900 justification for a legally binding Workplace Exposure Limits in Germany of

8 mg/m³ (1.3 ml/m³); long term

16 mg/m³ (2.6 ml/m³); short term (long term value can be exceeded by a factor of 2)

The dichlorotoluene mixture shows only very low toxicity (oral, dermal, inhalation) after acute administration. It is light to moderately irritating to skin and eyes and has no sensitizing potential in animal experiments on guinea pigs.

In an inhalation hazard test in rats with a saturated vapour atmosphere, at 95°C death occurred after an exposure of 7 hours. The autopsy showed evidence of a slight damage to lungs and liver.

Regarding the question of the toxicity of the dichlorotoluene mixture after repeated application, the results of a subacute oral toxicity study in rats are available.

The NOAEL for males is 100 mg/kg bw/day; in higher doses males revealed a slight hypertrophy of the central lobular hepatocytes, and kidney changes as a result of hyaline droplet accumulation, which manifests itself already in the 20 mg/kg group and which is considered as a species- and gender-specific phenomenon.

In females the NOAEL in this study was 500 mg/kg bw/day.

In the Ames test the dichlorotoluene mixture as well as the pure 2,4-dichlorotoluene is not mutagenic, and in the micronucleus test in mice the dichlorotoluene mixture shows no clastogenic effect .

In the subacute study in rats, there was no evidence of relevant effects on toxicity to reproduction. The effects reported in a publication after oral treatment with 2,4-dichloro-toluene are not taken into account due to the lack of validity of the study.

For the derivation of a guidance value only the results of the subacute oral toxicity study in rats are used. The NOAEL for a human relevant effect is 100 mg/kg bw/day.

Starting from a NOAEL of 100 mg/kg and a total extrapolation factor of 84 results yields a dose of 1.2 mg/kg bw/d. For humans the expert committee derived for a dose of 1.2 mg/kg bw/d, a human body weight of 70 kg and a tidal volume of 10 m³ during 8 hours a Workplace Exposure Limit value of 8 mg/m³.

Accordingly, the Committee derived a Workplace Exposure Limit (ARW) of 1.3 ppm = 8 mg/m³ with a Category II short term limit (long term value can be exceeded by a factor of 2 leading to 16 mg/m³ (2.6 ml/m³); short term). This guidance level is considered as sufficient to ensure the protection of exposed persons to potential hepatotoxic effects of dichlorotoluene mixture.