[No public or meaningful name is available]

Endpoint summary

Description of key information

Not harmful/toxic if swallowed

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:

February, from the 04th to the 20th, 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17th December 2001

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Species and strain: Crl:(WI)BR rats.
- Source: TOXI COOP ZRT. Budapest, Hungary.
- Females: nulliparous and non pregnant animals.
- Age at study initiation: young adult rat, 9 weeks old in first and second step.
- Weight at study initiation: 180 - 186 g first step; 180 - 184 g second step.
- Fasting period before study: the day before treatment the animals were fasted. The food but not water was withheld overnight.
- Housing: 5/II (E building). 3 animals/cage; cages type II polypropylene/polycarbonate.
- Diet: animals received ssniff® SM R/M-Z+H complete diet for rats and mic, ad libitum.
- Water: tap water from municipal supply, as for human consumption from bottle, ad libitum.
- Acclimation period: 12 days in first step and 13 days in second step.
- Animal health: only healthy animals were used for the study. Health status was certified by the study director.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C.
- Humidity: 30 - 70 %
- Air changes: 10-15 air exchanges/hour by central air-condition system.
- Photoperiod: artificial light, from 6 a.m. to 6 p.m.

Route of administration:

oral: gavage

Vehicle:

other: Helianthi annui ol. raffinat.

Details on oral exposure:

FORMULATION
- Treatment volume: 10 ml/kg bw.
- Concentration: 200 mg/ml.
- Preparation: formulations were prepared just before the administration and stirred continuously during the treatment.

DOSE SELECTION
Starting dose was selected on the basis of the available information about the test item.
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.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 animals/group

Details on study design:

- Duration of observation period following administration: fourteen-day observation period.
- Frequency of observations for 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.
- Frequency of observations for mortality: animals were weighed before the application and the food was given back 3 hours after the treatment. The body weights were recorded on day 0 (just before the treatment), on day 7 and on day 15 with a precision of 1 g.
- General state, external appearance, behavior and clinical symptoms: 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 membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: necropsy on Day 15. 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.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mL/kg bw

Based on:

test mat.

Mortality:

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

Clinical signs:

other: In group 1 treated with 2000 mg/kg bw dose clinical sign of reaction comprised of brownish-red coloured faeces (6 cases of 57 observations). This symptom (score +4; +3) was detected in all animals on Day 1 and on Day 2. In group 2 treated with 2000 mg/kg

Gross pathology:

All animals survived until the scheduled necropsy on Day 15.
Slight hydrometra was observed in female No.: 8 of the group 1 and in female No.: 11 of the group 2. It is physiological finding and connected to the cycle of the animal.
No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.

Interpretation of results:

other: not classified, according to the CLP Regulation (EC) No 1272/2008

Conclusions:

LD50 (female, rat) > 2000 mg/kg bw

Executive summary:

An acute toxic class method was carried out according to the OECD guideline 423. The experiment involved 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. 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 survived until the end of the 14-day observation period. In the first step, brownish-red coloured faeces was observed in animals between Day 1 and Day 2. In the second step, brownish-red coloured faeces was observed in animals between Day 1 and Day 2. The observed clinical sign as brownish-red coloured faeces was not related to the systemic toxic effect of the test item, but this alteration was connected with the physical property of the test item. The body weight development was undisturbed in all animals.

Slight hydrometra was observed in one female of the group 1 and in one female of the group 2; this physiological finding is connected to the cycle of the animal. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.

Conclusion

LD50 (female, rat) > 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

ACUTE TOXICITY BY ORAL ROUTE

An acute toxic class method was carried out according to the OECD guideline 423. The experiment involved a stepwise procedure with the use of 2000 mg/kg bw as dosage. No death occurred during the study. All rats dosed at 2000 mg/kg bw test item survived until the end of the 14-day observation period. In the first step, brownish-red coloured faeces was observed in animals between Day 1 and Day 2. In the second step, brownish-red coloured faeces was observed in animals between Day 1 and Day 2. The observed clinical sign as brownish-red coloured faeces was not related to the systemic toxic effect of the test item, but this alteration was connected with the physical property of the test item. The body weight development was undisturbed in all animals. Slight hydrometra was observed in one female of the group 1 and in one female of the group 2; this physiological finding is connected to the cycle of the animal. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.

ACUTE TOXICITY BY INHALATION ROUTE

No acute toxicity studies by inhalation route are available on Yellow LF 6881.

Because of the physical state and the trade forms of the substance inhalation is not an appropriate route of exposure. Particle size distribution showed that Yellow LF 6881 is characterized by particles that are expected to remain in the upper respiratory tract, which is characterized by efficacious defence mechanisms able to remove them. The sieve analysis indicated that the particle size distribution: for the test item is within 45 - 1000 µm.. In particular, particles with a diameter lower than 100 µm are 35.5 % and the particles with a diameter lower than 45 µm are 0.9 %. From this point of view, inhalation route is expected to be an unlikely route of absorption of the substance.

ACUTE TOXICITY BY DERMAL ROUTE

The inhalation and the skin contact of Yellow LF 6881 are unlikely. Furthermore, because of the physical/chemical properties of the substance, the dermal absorption is expected as negligible.

According to the Commission Regulation (EU) 2016/863, amending Annexes VII and VIII to REACH Regulation (EC) No 1907/2006, testing by the dermal route does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in viv ostudies with dermal exposure (e.g. skin irritation, skin sensitisation).

It is explained that scientific analysis of available data from in vivo acute toxicity studies have shown that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. Therefore, testing those substances via the dermal route does not provide essential information for their safety assessment.

The skin sensitisation assay has been performed on the Yellow LF 6881; the allergenic potential of the substance was examined in a LLNA test system, according to the OECD guideline 429. No mortality , no significant treatment related effect on body weights, any other signs of systemic toxicity or any sign of significant irritation or any other local effect were observed in any treatment group during the test. Visual appearance of the lymph nodes was normal in the test item treated. Yellow LF 6881 has no skin sensitization potential.

In addition, the substance does not meet the criteria to be classified as STOT SE by oral route.

In conclusion, because of the dermal absorption and the systemic toxicity potentials, no further investigation is proposed.

Justification for classification or non-classification

According to the CLP Regulation (EC) No 1272/2008, 3.1 acute toxicity section, substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to the numeric criteria. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE).

The oral LD50 value was established to be greater than 2000 mg/kg, therefore the test substance is out of any classification limit for acute oral toxicity (oral acute toxicity category 4: 300 < ATE ≤ 2000 mg/kg bw).

Dermal and inhalation are considered as negligible exposure routes, thus no acute toxicity tests have been conducted and no further investigations are required.

In conclusion, the test substance does not meet the criteria to be classified for oral acute toxicity, according to the CLP Regulation (EC) No 1272/2008.