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Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
Only abstract available, no detailed documentation. Further restrictions: 15 rats per group at termination (20 recommended); no ophthalmological examination; no functional observations; dose-response data not clearly reported for all parameters.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Support: Letter from Dow Corning Corp to USEPA regarding studies or reports on N-Methyl Acetamide with Attachments, date 01/03/97
Author:
DOW Corning Corp.
Year:
1997
Bibliographic source:
NTIS/OTS 0537230-1
Reference Type:
publication
Title:
Letter submitting information on a ninety-day water feeding study with N-methylacetamide on rats
Author:
DOW Corning Corp.
Year:
1992
Bibliographic source:
NTIS/OTS 0537230
Reference Type:
publication
Title:
Letter from Dow Corning Corp. to US EPA submitting results of 90-day water feeding study with N-methylacetamide
Author:
DOW Corning Corp.
Year:
1990
Bibliographic source:
NTIS/OTS 0530468

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Deviations:
no
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
N-methylacetamide
EC Number:
201-182-6
EC Name:
N-methylacetamide
Cas Number:
79-16-3
Molecular formula:
C3H7NO
IUPAC Name:
N-methylacetamide
Details on test material:
no details

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
no details

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Details on oral exposure:
Test substance in water to produce a nominal exposure of 0, 50, 400, or 1000 mg/kg bw/day;
no further details
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
90 days
Frequency of treatment:
daily ad libitum
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 50, 400 or 1000 mg/kg bw/day
Basis:
nominal in water
No. of animals per sex per dose:
Initial: 20
30 days after initiation 5 rats per sex per dose were sacrificed for blood collection and analysis.
At termination: 15
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: a satellite group (n=15 per sex) was started at the high dose level but no data were reported in the result section except mortality data.
Positive control:
no

Examinations

Observations and examinations performed and frequency:
Body weight, food consumption, water consumption, and clinical observations throughout the study (no further details).
At termination "clinical pathology" was made (presumably hematology and clinical chemistry; no details).
Sacrifice and pathology:
At the termination of the study after 90 days, complete gross necropsy & histopathological evaluations.
No further details.
Other examinations:
no
Statistics:
no data

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Description (incidence):
1000 mg/kg bw/day: in males and females increased mortality (50%)
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
1000 mg/kg bw/day: in males and females significantly reduced body weights
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
1000 mg/kg bw/day: significantly reduced food consumption
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Description (incidence and severity):
1000 mg/kg bw/day: in males and females significantly reduced water consumption.
400 mg/kg bw/day: in females significantly reduced water consumption.
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
>=50 mg/kg bw/day: absolute and/or relative organ weights were significantly different compared to control for spleen, kidneys, adrenals, brain, testes, and liver (no details, especially on dose-response relationship).
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
>= 50 mg/kg bw/day: in males dose dependent tubular nephrosis (minimal at low dose levels)
1000 mg/kg bw/day: in females tubular nephrosis; in males and females the liver, bone marrow, lymph nodes, thymus, eyes and Harderian glands with histological changes (hypoplasia in bone marrow, lymph nodes and thymus; no further details); eye lesions considered to be related to an inflammatory condition observed in the Harderian glands. Hepatic changes are non-specific and composed of a variety of diagnoses. Many males of the high dose group had epididymal aspermia, seminiferous tubule atrophy, and reduced seminal vesicle secretory activity. No effects reported at lower dose levels.
Histopathological findings: neoplastic:
no effects observed

Effect levels

open allclose all
Dose descriptor:
NOAEL
Remarks on result:
not determinable
Remarks:
no NOAEL identified
Dose descriptor:
LOAEL
Effect level:
50 mg/kg bw/day (nominal)
Sex:
male
Basis for effect level:
other: tubular nephrosis (toxicological relevance at this dose unclear)
Dose descriptor:
LOAEL
Effect level:
50 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: effects on organ weights; not clearly stated

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Clearly toxic effects in a subchronic drinking water study in rats at 1000 mg/kg bw; in males tubular nephrosis at >= 50 mg/kg bw/day but the toxicological relevance is unclear.
Executive summary:

Comparable to guideline study with acceptable restrictions (only abstract available, no detailed documentation but sufficient for evaluation). Further restrictions: 15 rats per group at termination (20 recommended); no ophthalmological examination; no functional observations; dose-response data not clearly reported for all parameters.

In a drinking water study 20 rats per dose per sex were exposed to 0, 50, 400, 1000 mg/kg bw/day (nominal) for 90 days. After 30 days a subgroup of 5 rats per dose per sex were sacrificed for blood analysis. At 1000 mg/kg bw/day males and females revealed increased mortality (50%), significantly reduced body weights and significantly reduced food and water consumption; in females at 400 mg/kg bw/day also significantly reduced water consumption was measured. At >= 50 mg/kg bw/day absolute and/or relative organ weights were significantly different compared to control for spleen, kidneys, adrenals, brain, testes, and liver (no details, especially on dose-response relationship). Histopathology: at >= 50 mg/kg bw/day dose dependent tubular nephrosis (minimal at low dose levels) in males was found and at 1000 mg/kg bw/day also in females. At 1000 mg/kg bw/day the liver, bone marrow, lymph nodes, thymus, eyes and Harderian glands revealed in males and females histological changes (hypoplasia in bone marrow, lymph nodes and thymus; no further details); eye lesions considered to be related to an inflammatory condition observed in the Harderian glands. Hepatic changes are non-specific and composed of a variety of diagnoses. In males reproductive organs were affected at 1000 mg/kg bw/day: epididymal aspermia, seminiferous tubule atrophy, and reduced seminal vesicle secretory activity.

Conclusion: Clearly toxic effects in a subchronic drinking water study in rats at 1000 mg/kg bw; in males tubular nephrosis at >= 50 mg/kg bw/day but the toxicological relevance is unclear.