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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: study design is not according to the requirements of today and the report of results is only in brief

Data source

Reference
Reference Type:
publication
Title:
Maximum permissible concentration of trimethylolpropane (etriol) in factory air
Author:
Stankevich, V.V.:
Year:
1967
Bibliographic source:
Hygiene and Sanitation 32(5), 288-291

Materials and methods

Principles of method if other than guideline:
rats were exposed to different concentrations of TMP for 3.5 months, observed for signs of toxicity, weight development, hematological effects, mortality. Following sacrifice pathological and histopathological examination
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no data

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
details not given

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
other: air
Remarks on MMAD:
MMAD / GSD: no data
Details on inhalation exposure:
rats in chambers were subjected to to a 4 hour dynamic exposure to the substance . The air supplied to the chambers was previousely passed through a tube with the preparation placed on a boiling water bath
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
TMP was determined chemically according to the method elaborated at the Industrial Sanitary and chemical Laboratory of the Kiev Occupational health Institute. The method is based on the formation of an orange-brown compound when p-dimethylaminobenzaldehyde reacts with TMP in sulfuric acid medium
Duration of treatment / exposure:
3.5 months
Frequency of treatment:
daily for 4 hours but details not given
Doses / concentrations
Remarks:
Doses / Concentrations:
0.13 mg/l (0.1-0.7 mg/l); 1.1 mg/l (0.7-1.8 mg/l)
Basis:
no data
No. of animals per sex per dose:
20
Control animals:
yes
Details on study design:
The toxic effects of the substance was assessed from the time required for the development of poisoning its course and outcome, the morphological composition of the blood, the threshold of neuromuscular excitability, the body weights, the ratio of weight of organs to the weight of body and pathomorphologic alterations in internal organs, no post exposure observation time
Positive control:
no

Examinations

Observations and examinations performed and frequency:
The toxic effects of the substance was assessed from the time required for the development of poisoning, its course and outcome, the morhological composition of the blood, the threshold of neuromuscular excitability, the body weights:
relative weights of the brain, heart, liver, lungs, kidneys and spleen
Sacrifice and pathology:
the ratio of weight of organs to the weight of body and pathomorphologic alterations in internal organs
Other examinations:
hematology
Statistics:
the significance of reactions of the control and the experimental animals and the scatter of resulting data were estimated by statistical analysis (Belen'kii)

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
no effects observed
Details on results:
ORGAN WEIGHTS
the relative weights of the brain, heartm liver, lungs, kidneys and spleen had not been changed by exposure to both concentrations of TMP. There was only an increase in the relative weights of the suprarenals which was statistically significant in the experimental mean concentration of 1.1 mg/l

GROSS PATHOLOGY / HISTOPATHOLOGY (NON-NEOPLASTIC)

disturbance of blood circulation, slight disturbance of the permeability of the vessel walls, parenchymatous degeneration of the liver, interstititial pneumonia, focal emphysema, moderate parenchymatous degeneration of heart and kidneys

FURTHER FINDING
dysfunction of the nervous system: threshold of neuromuscular excitability raised after exposure to 1.1 mg/l (beginning with the 8th w of the experimental period) and also after exposure to 0.13 mg/l (beginning with the 12th w); 

Effect levels

Dose descriptor:
NOAEC
Effect level:
ca. 0.13 mg/L air
Sex:
not specified
Basis for effect level:
other: According to the author the arbitrary threshold concentration was taken to be 0.13 mg/l (130 mg/m³): no clinical signs but histopathological changes in lungs, liver, and kidneys at higher dosages

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

RS-Freetext:
both experimental series: no outward signs of poisoning,
normal food intake and weight gain; hematology: no change in
RBC, WBC and hemoglobin values;  dysfunction of the nervous
system: threshold of neuromuscular excitability raised
after exposure to 1.1 mg/l (beginning with the 8th w of the
experimental period) and also after exposure to 0.13 mg/l
(beginning with the 12th w); unchanged relative weights of
the brain, heart, liver, lungs, kidneys and spleen
1.1 mg/l: increase in the relative weight of the
suprarenals concentration unspecified: parenchymatous
degeneration of the liver, interstitial pneumonia and focal
emphysema, moderate parenchymatous degeneration in the
heart and kidneys

Applicant's summary and conclusion

Executive summary:

Rats were exposed 4 hours daily over a period of 3.5 months to exposure concentrations ranging from 0.1 to1.8 mg/l (corresonding to 100 -1800 mg/m³) Rats exhibited no signs of toxicity and no animal died.Weight gain was comparable to the concurrent control. Histopathological changes involved lungs , heart and kidneys; a NOAEC was determined to be 130 mg/m³ (Stankevich 1967)