long chain alkyl thio carbamide metal complex

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15-May-2002 to 14-Jun-2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): MRD-02-375
- Physical state: red viscous liquid
- Analytical purity: "the test substance, as received, was considered 'pure' substance"
- Expiration date of the lot/batch: April 2007
- Stability under test conditions: "the testing laboratory characterized the neat test substance and will determine its stability when the final characterization is performed"
- Storage condition of test material: room temperature
- Other: pH: 5

Test animals

Species:

rat

Strain:

other: Crl: CD (SD) IGSBR

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, NY
- Age at study initiation: 10-13 weeks
- Weight at study initiation: 217-257 g
- Fasting period before study: yes, overnight
- Housing: singly housed in suspended stainless steel and wire mesh cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7-22 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 15-May-2002 To: 14-Jun-2002

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.5 g/ml (50% w/v)
- Amount of vehicle (if gavage): 4 ml/kg bw
- Justification for choice of vehicle: standard vehicle in toxicology studies; test substance is mixed with lubricant base oil in the final product
- Lot/batch no. (if required): Sigma, product number C8267, lot number 70K0 127
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 4 ml/kg bw

DOSAGE PREPARATION (if unusual): "The test substance was mixed with the carrier to form a dosable mixture"

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 females tested

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- viablility: twice daily Monday through Friday and once daily on weekends and holidays
- clinical observations: at 30 minutes, 1, 2, 4 and 6 hours after dosing and once per day thereafter for a total of 14 days
- body weight: on the day prior to dosing (pretest), on the day of dosing (day 0), on day 7 and on day 14
- Necropsy of survivors performed: yes
- Other examinations performed:
- clinical signs: the nature, onset, severity, and duration of toxicological signs
- body weights
- gross necropsy: performed on all animals; included an examination of the external surface of the body, all orifices, the cranial, thoracic and abdominal cavities and their contents

Statistics:

Means and standard deviations of body weight and body weight change calculated by group and sex

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

0/5

Clinical signs:

Present in 2/5: wet rales were evident in one animal from the 1 hour observation through to day 2, and alopecia of the trunk was seen in a rat on day 4 until study termination. Clinical signs were not reported at the other observation periods for these animals.
Absent in 3/5: all remaining animals were free of observable abnormalities throughout the study.

Body weight:

All animals displayed increases in body weight over their initial values

Gross pathology:

Effects on organs: all animals were free of gross postmortem abnormalities with the exception of the one animal that displayed alopecia of the trunk

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a GLP study conducted according to OECD guideline 425, the acute oral LD50 of EC# 457-320-2 was >2000 mg/kg bw (the limit dose) in female rats.

Executive summary:

In a GLP study conducted according to OECD guideline 425, EC# 457-320-2 was administered by oral gavage to five female rats at 2000 mg/kg bw, the limit dose. The animals were observed for clinical signs of toxicity and body weights were recorded over a 14-day observation period. A gross necropsy examination was performed at study termination.

There were no deaths reported. Two animals exhibited clinical signs of toxicity: wet rales were evident in one animal from the 1-hour observation through to Day 2, and alopecia of the trunk was seen in a rat on Day 4 until study termination. There were no clinical signs in the remaining three animals and all rats displayed increased body weights over their initial values. All animals were free of gross postmortem abnormalities with the exception of the one rat that displayed alopecia of the trunk.

In conclusion, the acute oral LD50 of EC# 457-320-2 is >2000 mg/kg bw in female rats. In accordance with EU CLP regulations, the substance would not need to be classified as acutely toxic via the oral route.