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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:
other: No GLP and no guideline study. The study has methodological deficiencies and is insufficient reported.

Data source

Reference
Reference Type:
publication
Title:
Short-term test systems to assess thiophosphoryl chloride standards
Author:
Colosi-Esca D, Snca Z, Barbarino F, Surcel D, Papilian VV
Year:
1984
Bibliographic source:
J. Appl. Toxicol. 4, 230-235

Materials and methods

Principles of method if other than guideline:
Thiophosphoryl trichloride in vegetable oil was mixed with dried milk powder and administered in warm water and given to female rats each morning 6 days a week prior to replenishing food hoppers. Body weights were measured weekly, relative organ weights, clotting time, gross and histopathological changes, hematological parameters, blood biochemical parameters (results were shown as graphics).
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no details given

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Body weight at the beginning : approximately 105 g
no further data given

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: vegetable oil mixed in dried milk powder administered in warm water
Details on oral exposure:
Given each morning on 6 days per week for 90 days prior to replenishing the food hoppers.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Frequency of treatment:
6 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
7.5 or 37.5 mg/kg bw
Basis:

No. of animals per sex per dose:
Groups of 20 female rats
Control animals:
yes, concurrent vehicle
Details on study design:
Thiophosphoryl trichloride in vegetable oil was mixed with dried milk powder and administered in warm water and given to female rats each morning 6 days a week prior to replenishing food hoppers. Body weights were measured weekly, relative organ weights, clotting time, gross and histopathological changes, hematological parameters, blood biochemical parameters. Post-exposure period: no
Positive control:
no

Examinations

Observations and examinations performed and frequency:
DETAILED CLINICAL OBSERVATIONS No data

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes
total blood hemoglobin, hematocrit, mean corpuscular hemoglobin comcentration, differential leucocyte counts,

CLINICAL CHEMISTRY: Yes
serum alkaline phosphatase, serum cholin esterase, serum glutamate-oxalate transaminase, serum glutamate-pyrovate transaminase, total serum protein, u.a.

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
relative organ weights: liver, heartm spleen, kidney and adremals gross changes

HISTOPATHOLOGY: Yes
changes in the above organs , histoenzymical changes in liver and gastric mucosa
Other examinations:
no data
Statistics:
Student's t-test

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
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:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
no effects observed
Details on results:
i

Effect levels

open allclose all
Dose descriptor:
NOAEL
Remarks on result:
not determinable
Remarks:
no NOAEL identified
Dose descriptor:
LOAEL
Effect level:
ca. 7.5 mg/kg bw/day (actual dose received)

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Data were presented as graphics only:
Increased growth rate in both dose groups, no dose related effect on organ weights, increase of liver transaminase activity in serum, decreased acid secretion in gastric mucosa, in the high dose group slight liver
dystrophic histopathological changes.

Applicant's summary and conclusion

Executive summary:

Groups of 20 female Wistar rats were given 0, 7.5 and 37.5 mg/kg bw/day thiophosphoryl trichloride in vegetable oil which was mixed with dried milk powder and administered in warm water, each morning, 6 days a week for 90 days, prior to replenishing food hoppers. A NOAEL could not be determined based in inconsistant responses in relative organ weights and biochemical and histochemical results. The LOAEL is 7.5 mg/kg bw/day under the condition of this investigation (Colosi-Esca 1984).