Registration Dossier

Administrative data

Description of key information

The available oral and dermal LD50 values and the calculated 4-h inhalation LC50 value of DCM are all above the classification cut-offs. In rats, administration of 2000 mg/kg bw did not induce mortality, either via the oral or the dermal route. In the mouse, an inhalation 7-hour LC50 value of 49000 mg/m3 has been reported which was recalculated into a 4-h LC50 value of 86000 mg/m3 taking Haber’s rule into account.

The oral and dermal LD50 values and the inhalation LC50 values indicate that the acute toxicity of dichloromethane is low.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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: OECD Guideline 401 and GLP-compliant study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
SPF-derived males (180-200 g) and femals (160-180 g) at arrival
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
once, 14 days observation period
Doses:
2000 mg/kg bw (dose volume: 5 ml/kg)
No. of animals per sex per dose:
5/sex/dose
Control animals:
yes
Details on study design:
For ethical reasons the control group was used for a number of studies which were carried out in parallel.

Investigated parameters: clinical signs, body weights and body weight gains, autopsy, organ weights and histopathology.
Statistics:
The results were evalulated with an analysis of variance followd by a Student t-test (two-sided).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Mortality was not observed.
Clinical signs:
The clinical signs were indicative of an effect on the:
- autonomic nervous system (decreased respiratory rate, respiratory difficulties, ptosis, piloerection and salivation)
- central nervous system (possitional passivity, twitches and convulsions)
- motor- coordination and -activity (abnormal gait and posture, catalepsy, loss of righting reflex and decreased activity)
- muscle tone (diminished body tone and paralysis).
Body weight:
The treated rats gained less weight than the control animals in the first few days after dosing. Thereafter the animals recovered and their weight gain appeared normal.
Gross pathology:
Examination of the rats revealed swollen or slighty swollen livers in all treated animals.
No treatment related effects on absolute and relative organ weights were observed.
Other findings:
Microscopic examination of the tissues revealed no clear changes attributable to treatment in the males. Four females showed hydropic degeneration of liver parenchchyma cells and three females showed cloudy swelling of the renal cortical tubules. However, changes in degree and incidence were too slight to warrant any firm conclusion as to whether they were treatment related.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 was in excess of 2000 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
LD50 in excess of 2000 mg/kg bw; quality database is OK

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication, predates OECD guidelines and GLP, minor restrictions in design and reporting, but otherwise adequate for assessment
Principles of method if other than guideline:
Mice were exposed for 7 h by whole-body exposure to dichloromethane vapour in a 15-L bell jar.
GLP compliance:
no
Test type:
other: 7-hour whole body exposure
Limit test:
no
Species:
mouse
Strain:
Swiss Webster
Sex:
not specified
Details on test animals and environmental conditions:
White Swicce mice of approx. 20 g body weight were used
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Mice were exposed in a bell jar of approximately 15 liters capacity.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
7 h
Concentrations:
53.5, 45.6, 47.7 and 39.9 mg/l (determined) (154000, 13126, 13730 and 11485 ppm)
No. of animals per sex per dose:
20/concentration
Control animals:
no
Details on study design:
The observation period was one day.
Sex:
not specified
Dose descriptor:
LC50
Effect level:
49 000 mg/m³ air
Based on:
test mat.
Exp. duration:
7 h
Clinical signs:
other: The animals became restless, developed muscular twitchings, uncoordinated movements, labored respiration, and narcosis.

Table 1. The acute toxicity of vapours of dichloromethane for mice.

Concentration in air

 

 

 

 

 

 

Number of fatalities following exposure

 

 

Calculated

 

Determined

 

Hours

 

mg/liter

ppm

mg/liter

ppm

8

24

 58.70

16.897 

53.5 

15.400 

18/20 

 

 55.55

15.990 

45.6 

13.126 

4/20 

5/20 

 52.94

15.239 

47.7 

13.730 

2/20 

 

 44.45

12.795 

39.9 

11.485 

0/20 

 

Interpretation of results:
GHS criteria not met
Conclusions:
Because the 4-h LC50 value (calculated from a 7-h value) was 86 mg/L, and no delayed mortality was expected, no classification is needed for acute inhalation toxicity.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
49 000 mg/m³
Quality of whole database:
Quality database is OK.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Although application area was rather small, this was not considered to have significantly influenced the outcome of the study; OECD Guideline 402 and GLP-compliant study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
SPF-derived males (180-200 g) and femals (160-180 g) at arrival.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
applicaton surface was 15 cm2
Duration of exposure:
24 hours, 14 days observation period
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex/dose
Control animals:
yes
Details on study design:
For ethical reasons the control group was used for a number of studies which were carried out in parallel. The data of this group are filed under study no. DT 88/17.

Investigated parameters: clinical signs, body weights and body weight gains, autopsy and organ weights.
Statistics:
The results were evalulated with an analysis of variance followd by a Student t-test (two-sided).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Mortality was not observed.
Clinical signs:
Vocalization was observed in the first half an hour of treatment in all males and 2 females. All males of the treated group and one female of the control group were a little bit quiet. At 1 .5 hours after application period signs had disappeared.
Body weight:
The animals showed normal weight gain
Gross pathology:
4 males and 4 females showed swollen or slightly swollen livers (compared with 1 male and 1 female in the controls).
Absolute and relative liver weights of the males were statistically significantly decreased.

Other findings:
No effects were observed.
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 > 2000 mg/ktg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
LD50 in excess of 2000 mg/kg bw. Quality database is OK.

Additional information

The acute toxicity of dichloromethane by inhalation, oral and dermal administration is low.

Based on animal studies, DCM does not need to be classified for acute toxicity for any route of exposure. LD50 values of > 2000 mg/kg bw were determined in an oral and dermal toxicity study with rats (guideline studies). In a well-documented publication a 7 -h LC50 of 49 mg/Lair was determined in mice; based on Haber’s rule, this corresponds to a 4 -h LC50 value of 86 mg/L. Although the observation period was only one day, it was noted that only one more animal died between 8 and 24 h. Based on the clinical signs noted, an acute effect rather than a long-term effect seemed to have been present, and as such no delayed mortality is expected. As such a 4-h LC50 value of 86 mg/L is far above the classification limit of 20 mg/L, and therefore no classification is needed for acute inhalation toxicity.

  

With regard to non-lethal toxicity, adverse effects were observed in humans (case and experimental studies).The principal effects were effects on visual-manual tasks and carbon monoxide intoxication. The effects on visual-manual tasks became apparent at lower concentrations than those causing carbon monoxide intoxication. The lowest LOAEC observed (see 7.10.3) was equal to 200 ppm (0.706 mg/L) for a 4 -h exposure. Decreased tracking performance and a decline in the response time in the visual-peripheral component of dual tasking were observed. In this study no NOAEC was obtained but in another study (see 7.10.2), systemic effects in humans exposed to 100 ppm (0.353 mg/L) for 8 h/day for a period of three days were not observed. Based on possible short-term pre-narcotic effects, the SCOEL recommends a STEL (15 min) of 200 ppm (0.706 mg/L). This value will be used as DNEL for acute inhalation exposure.

 

Justification for selection of acute toxicity – oral endpoint

OECD Guideline 401 and GLP-compliant study

Justification for selection of acute toxicity – inhalation endpoint

Acceptable, well-documented publication, predates OECD guidelines and GLP, minor restrictions in design and reporting, but otherwise adequate for assessment

Justification for selection of acute toxicity – dermal endpoint

Although application area was rather small, this was not considered to have significantly influenced the outcome of the study; OECD Guideline 402 and GLP-compliant study

Justification for classification or non-classification

On the basis of the observed CNS effects in human studies, dichloromethane should be regarded as a substance which produces vapours that may cause drowsiness and dizziness (R67) according to Directive 67/548/EEC. According to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the substance should be classified as STOT - Single exposure Cat 3; H336.

 

Based on the oral and dermal LD50 and inhalation LC50 values, classification for acute toxicity is not warranted according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.