(2S)-2-amino-3-[3,5-diiodo-4-(4-methoxyphenoxy)phenyl]propanoic acid

Endpoint summary

Description of key information

An acute toxic class method was carried out: No death occurred at 2000 mg/kg bw single oral dose of O-METHYL-L-DIIODOTHYRONIN. All female rats in step 1 and step 2 survived until the end of the 14-day observation period.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 January 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

Test Item Name: O-METHYL-L-DIIODOTHYRONIN
Batch No.: B488840
Appearance: white, powder
CAS Number: 94345-95-6
Expiry date: 24 Sept. 2020
Storage conditions: room temperature, protected from light

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species and strain: Han:WIST rats
Source: TOXI COOP ZRT. Cserkesz u. 90.
1103 Budapest, Hungary
Hygienic level at arrival: SPF
Hygienic level during the study: Good conventional
Justification of strain: The Wistar rats as a rodent is one of the standard species of acute toxicity studies
Number of animals: 3 animals/group
Sex: Female, nulliparous and non pregnant animals
Age of animals: Young adult rat, 8-9 weeks old in first and second step
Body weight range
at starting (first step): 168 - 170 g
Body weight range
at starting (second step): 170 - 173 g
Acclimatization time: 7 days in first step and 8 days in second step.
Animal health: Only healthy animals were used for the study. Health status was certified by the study director.
Room: 13/1
Housing: Group caging (3 animals/cage)
Cage type: Type III. polypropylene/polycarbonate.
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 - 70 %
Ventilation: above 10 air exchanges/hour by central air-condition system.
The temperature and relative humidity parameters were recorded daily during the study.

Route of administration:

oral: gavage

Vehicle:

water

Doses:

All doses were formulated in the vehicle. Concentration of formulations was adjusted to maintain a treatment volume of 10 mL/kg bw. The test item was applied in a concentration of 100 mg/mL. Formulations were prepared just before the administration.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

A single oral administration - followed by a fourteen-day observation period - was performed by gavage. The day before treatment the animals were fasted. The food but not water was withheld overnight. Animals were weighed before the application and the food was given back 3 hours after the treatment. The test item was administered in two fractions. At least 30 minutes were passed between the administrations of two fractions. 7 days in first step and 8 days in second step of acclimatization, treatment’s day, 14 days post-treatment observation period, necropsy on Day 15.

Preliminary study:

Justification of the doses
The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 was met.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Animals were observed individually after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h after the treatment and twice each day for 14 days thereafter.

Clinical signs:

other: Animals were observed individually after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h, after the treatment and once each day for 14 days thereafter. Individual observations were performed on the skin and fur, eyes and mucous m

Gross pathology:

At the end of the observation period rats were sacrificed under isofluran anaesthesia. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed, and any abnormality was recorded with details of its location, colour, shape and size.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

No death occurred at 2000 mg/kg bw single oral dose of O-METHYL-L-DIIODOTHYRONIN. All female rats in step 1 and step 2 survived until the end of the 14-day observation period.

Executive summary:

General information:

An acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, therefore treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 (presented in Appendix VII) was met. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out 15th day after the treatment.

Lethality, Clinical symptoms and Body weight:

No death occurred during the study. All rats dosed at 2000 mg/kg bw test item O-METHYL-L-DIIODOTHYRONIN survived until the end of the 14-day observation period.

No clinical symptoms were observed on the day of the treatment and during the 14-day observation period, the general state and behaviour of experimental animals were normal.

The body weight development was undisturbed in all animals.

Gross pathology:

Six animals were sacrificed as scheduled during the study. All organs of all experimental animals proved to be free of treatment related gross pathological changes.

Evaluation:

The method used is not intended to allow the calculation of a precise LD50 value.

The test item was ranked into classes of Globally Harmonized Classification System (GHS) described in the OECD Guideline No. 423 as below:

Dose (mg/kg bw)              Mortality (dead/treated)                     LD50 (mg/kg bw)              GHS category

2000                                    0/6                                                      ≥ 5000                                5 or unclassified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Justification for classification or non-classification

2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, therefore treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 (presented in Appendix VII) was met. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out 15th day after the treatment.