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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted before OECD guidelines were established. The major endpoint is cancerogenicity without evaluation of standard parameters for repeated dose toxicity (haematology, clinical biochemistry) and histopathological examinations were limited to the lungs and trachea. N(L)OELs can not be established based on the study results and the study is therefore not usefull for RA purposes.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Cancerogenität und chronische Toxizität inhalierten Dimethylsulfats.
Author:
Schlögel, F.A.
Year:
1972
Bibliographic source:
Dissertation, University Faculty of Medicines, Würzburg, Germany

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Animals were observed for at least 30 months after start of exposure. Examinations included clinical signs, mortality, body weights, lung weights, gross pathology and histopathology. Histopathological examination was restricted to lungs and trachea. When gross examination revealed a tumour in other tissues/organs, this tissue/organ was included for histopathological examination.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Dimethyl sulphate
EC Number:
201-058-1
EC Name:
Dimethyl sulphate
Cas Number:
77-78-1
Molecular formula:
C2H6O4S
IUPAC Name:
dimethyl sulfate
Details on test material:
- Name of test material (as cited in study report): Dimethyl sulphate
No further details are given.

Test animals

Species:
other: rat (1), mosue (2) and hamster (3)
Strain:
other: Wistar (1) and NMRI (2) and Syrian (3)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS rats
- Source: "Zentralinstitute für Versuchstierzucht", Hannover, Germany
- Weight at study initiation: 117 g to 332 g
- Housing: groups of 5, 10 or 15 animals per sex per cage
- Diet: standard diet "sniff M" ad libitum
- Water: tap water ad libitum

TEST ANIMALS: mouse
- Source: "Zentralinstitute für Versuchstierzucht", Hannover, Germany
- Weight at study initiation: 24.3 g to 36.9 g
- Housing: groups of 5, 10 or 15 animals per sex per cage
- Diet: standard diet "sniff M" ad libitum
- Water: tap water ad libitum

TEST ANIMALS: hamster
- Source: Fa. Rudi Schneider, Rottach-Egern or Fa. G. Ansers, Edenkoben
- Weight at study initiation: 60 g to 105 g
- Housing: groups of 3 to 7 animals per sex per cage
- Diet: standard diet "sniff M" ad libitum, salat, carrots, sunflower seeds and oat flakes
- Water: tap water ad libitum

No further details are given.

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
other: air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: an exposure chamber with a volume of 940.5 liters was used.
- Method of holding animals in test chamber: the exposure chamber was divided in three levels to hold more animals in the chamber at the same time.
- The DMS-gas-air mixture was induced into the chamber at different levels.
- Temperature, humidity, pressure in air chamber: all animals were maintained at 23°C and 60% relative humidity.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Gaschromatography was used for the quantitative verification of the DMS concentration in the chamber.
Duration of treatment / exposure:
approximately 15 months
Frequency of treatment:
6 hours per day either daily or twice a week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.0 ppm
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
0.5 ppm (2.6 mg/m3)
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
2 ppm (10.5 mg/m3)
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
34 ppm (175.35 mg/m3)
Basis:
nominal conc.
No. of animals per sex per dose:
(1) 5-15
(2) 5-15
(3) 3-16
Control animals:
yes
Details on study design:
no data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: animals were observed daily; in case of mortality, animals were autopsied.

BODY WEIGHT: Yes
- Time schedule for examinations: all animals were weighed twice per week prior exposure.

ORGAN WEIGHT: Yes
- Time schedule for examinations: removed lungs and tracheas were weighed before fixed and prepared for sections.

No further details are given.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
After macroscopic analysis, lung, trachea, liver, kidneys and organs with carcinomas were removed and fixed in BOUIN's solution and sections were prepared
HISTOPATHOLOGY: Yes
Sections from tissues including tumourous tissues were analysed histopathologic.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
effects observed, treatment-related
Description (incidence and severity):
treatment related in rats only
Details on results:
CLINICAL SIGNS AND MORTALITY
- A remarkable finding was the very low survival time in male and female rats.

HISTOPATHOLOGY: NON-NEOPLASTIC
- An increase in the incidence of inflammation of the lungs was reported in DMS-exposed animals in all species.
- Bronchiopneumonia occurred at about the same degree in control and DMS exposed animals.

HISTOPATHOLOGY: NEOPLASTIC
- The incidence of benign tumours of the subcutis and lungs and the incidence of animals with malignant respiratory tract tumours per number of animals examined with histological classification of the tumours is given.
- DMS exposure resulted in an increased incidence of malignant tumours in the respiratory tract (nose and lungs).
- Rats were most sensitive to the tumour inducing activity of DMS, while hamsters were the least sensitive.
- In all three animal species females appeared more sensitive than males.
- In female rats of the 10.5 mg/m3 group the incidence of lung adenomas was slightly higher than in control females.
- There were no indications that DMS exposure induced an increase in subcutaneous fibromas.
- The highest incidence of animals with treatment-related malignant respiratory tract tumours was found in rats exposed to 10.5 mg/m3 group.
- The incidence in the 2.6 mg/m3 group was distinctly lower although the total dose in the low dose group was comparable or higher than that in the 10.5 mg/m3 group.
- This lower incidence might be related to the lower mean survival time in the 2.6 mg/m3 group, which in its turn may be a consequence of the initially high exposure scheme applied to this group.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Inhalation exposure to DMS induced treatment-related tumours in rats only. In this context it must be realised that the exposure scheme applied for the sublethal concentration of 175.35 mg/m3 leads to a lower total dose than that used with the 2.6 and 10.5 mg/m3-groups. Moreover most animals of the sublethal group have been exposed four times only.