Dimethyl sulphate

Specific investigations: other studies

Administrative data

Endpoint:

mechanistic studies

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

DNA methylation, cell proliferation, and histopathology in rats following repeated inhalation exposure to dimethyl sulfate

Author:

Mathison BH, Frame SR, Bogdanffy MS

Year:

2004

Bibliographic source:

Inhal Toxicol 16: 581-92

Reference 2

Reference Type:

secondary source

Title:

EU Risk Assessment Report Dimethyl Sulphate

Author:

European Chemicals Bureau

Year:

2002

Bibliographic source:

EU RAR, Volume 12. Luxembourg 2002

Materials and methods

Principles of method if other than guideline:

other

GLP compliance:

no

Type of method:

in vivo

Endpoint addressed:

carcinogenicity

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

- Name of test material (as cited in study report): dimethyl sulphate
- Analytical purity: >97%
No additional details provided

Test animals

Species:

rat

Strain:

other: CrlCD:BR

Sex:

male

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

other: filtered air

Details on exposure:

no additional details

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

1, 2, 3, 4, 5, and 10 days for kinetics of DNA adduct accumulation evaluation and 5 consecutive days for DNA adduct persistence evaluation

Frequency of treatment:

6 hours/day

Post exposure period:

the animals were sacrificed at 1, 2, 3, 6, and 10 days after exposure

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 0.7, 4.0, 7.4 mg/m3 (mean chamber concentration)
Basis:
other: calculated

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0±0, 0.13±0.05, 0.77±0.14, and 1.42±0.28 ppm
Basis:
analytical conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
0.1 ppm, 0.7 ppm, or 1.5 ppm
Basis:
nominal conc.
target concentration in filtered air

No. of animals per sex per dose:

8 animals per exposure concentration

Control animals:

yes, concurrent vehicle

Details on study design:

no additional details

Examinations

Examinations:

Animals were observed prior to, during, and after each exposure for clinical signs of toxicity related to exposure. Animals were weighed three times weekly prior to exposure and at the end of daily exposures.

Positive control:

None

Results and discussion

Details on results:

Mean body weight was depressed in rats exposed to 1.5 ppm dimethyl sulphate for 5 or more consecutive days. Mean body weight of rats exposed for 5 consecutive days and then allowed an exposure-free period of 10 days, recovered to control values within 10 days. However, standard deviations and statistical analysis were not given in the report.

There were no additional clinical signs of toxicity observed among rats at any exposure concentration.

Accumulation of N7-methylguanine adducts and persistence in respiratory and olfactory mucosa and lung were time and dose dependent. In contrast, N3-methyladenine failed to achieve any significant concentration or time-related increases following repeated exposures. The ratio of picomoles of N7-methylguanine to N3-methyladenine was approximately 5:1. In control rats DNA methylation was not detected in respiratory or olfactory control tissues with the exception of a trace level of N7-methylguanine in 3 of 44 analyzed samples of respiratory and olfactory mucosa, which was judged to be due to RNA contamination. Treatment related methylation of DNA guanine in respiratory and olfactory mucosa showed both time and exposure-related increases and appeared to reach a steady state. N7- Methylguanine levels steadily accumulated to a maximum after 5 days of exposure and generally remained unchanged or decreased out to 10 days. In respiratory mucosa, a slight downward trend in N7-methylguanine levels was detected at day 10 in both 4.0 and 7.4 mg/m3-groups. In lung, peak accumulation times were slightly shorter and appeared at approximately day 3 for the 0.7 and 4.0 mg/m3- groups. For the 7.4 mg/m3 group, peak accumulation was slightly prolonged to day 4. Little methylation of DNA appeared to occur in lung at the lower exposure concentrations, and levels of N7-methylguanine for the 0.7 mg/m3 exposed group were similar to the background levels detected in some air-exposed controls. N7-Methylguanine levels decreased from respiratory-tract tissues following cessation of exposure. There appeared to be only minor differences between the persistence of N7- methylguanine in nasal respiratory or olfactory mucosa. Slopes derived from an apparent linear fit of means indicated first-order disappearance of N7-methylguanine.

Any other information on results incl. tables

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