Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral LD50 (male and female) > 5000 mg/kg bw

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:
November 09th and 29th, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: rats were supplied by charles River (UK) Ltd., Manston, Kent.
- Age at study initiation: approximately five to eight weeks old.
- Weight at study initiation: males weighed 145 - 167 g, and the females 138 - 148 g.
- Fasting period before study: overnight fast immediately before dosing and for approximately two hours after dosing.
- Housing: the animals were housed in groups of up to five by sex in solid-floor polypropylene cages with sawdust bedding.
- Diet: free access to food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.).
- Water: free access to mains drinking water.
- Acclimation period: a minimum acclimatisation period of at least five days.

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 25 °C
- Relative humidity: 48 - 79 %
- Air changes: approximately 15 changes per hour.
- Photoperiod: the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
- Concentration: 500 mg/ml
- Dose volume: 10 ml/kg

PREPARATION OF TEST ITEM
For the purpose of the study the test material was freshly prepared, as required, as a solution at the appropriate concentration in distilled water. Homogeneity was assured by the use of a Silverson Homogeniser.
The composition and stability of the test material and the stability of the preparations were not determined.
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
Five males and five females
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: deaths and overt signs of toxicity were recorded 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
- Frequency of weighing: individual bodyweights were recorded on the day of treatment (day 0) and on days 7 and 14.
- Necropsy of survivors performed: at the end of the study the animals were killed by cervical dislocation and subjected to gross necropsy examination for any macroscopic abnormalities. This consisted of opening the abdominal and thoracic cavities and examining all major organs. The macroscopic appearance of abnormal organs if present was recorded. No tissues were retained.

RANGE-FINDING
- No animals per dose: 1 male and 1 female.
- Doses: 5000, 2000 and 200 mg/kg bw
- Concentration: 500, 200 and 20 mg/ml
- Dose volume: 10 ml/kg
- Observation: deaths and overt signs of toxicity were recorded 1/2, 1, 2 and 4 hours after dosing and then daily for five days. Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.
Preliminary study:
No deaths occurred.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No deaths occurred.
Clinical signs:
Signs of hunched posture were commonly noted during the study. Isolated incidents of noisy respiration, lethargy and vocalisation were also noted.
Animals appeared normal throughout the study for one to four days after dosing.
Yellow-coloured staining of the fur was commonly noted during the study.
Body weight:
No toxicologically significant effects on bodyweight were noted.
Gross pathology:
No abnormalities were noted at necropsy of animals killed at the end of the study.
Interpretation of results:
other: not classified, according to the CLP Regulation (EC 1272/2008)
Conclusions:
LD50 (male and female) > 5000 mg/kg bw
Executive summary:

A study was performed to assess the acute oral toxicjty of the test material in the Sprague-Dawley strain rat. The method used followed OECD guideline 401.

Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material preparation, administered as a solution in distilled water at a dose level of 5000 mg/kg bodyweight.

There were no deaths. Signs of hunched posture were commonly noted during the study. Isolated incidents of noisy respiration, lethargy and vocalisation were also noted. Animals appeared normal throughout the study or one to four days after dosing. Yellow-coloured staining of the fur was commonly noted during the study.

No toxicologically significant effects on bodyweight were noted. No abnormalities were noted at necropsy of animals killed at the end of the study.

The acute oral median lethal dose (LD50) of the test material in the sprague-Dawley strain rat was found to be greater than 5000 mg/kg bodyweight.

Conclusion

LD50 (male and female) > 5000 mg/kg bw

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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

ORAL ACUTE TOXICITY

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley strain rat. The method used followed that described in OECD guideline 401.

Following a range-finding study, a group of ten fasted animals was given a single oral dose of test material preparation, administered as a solution in distilled water at a dose level of 5000 mg/kg bodyweight. There were no deaths. Signs of hunched posture were commonly noted during the study. Isolated incidents of noisy respiration, lethargy and vocalisation were also noted. Animals appeared normal throughout the study for one to four days after dosing. Yellow-coloured staining of the fur was commonly noted during the study. No toxicologically significant effects on bodyweight were noted. No abnormalities were noted at necropsy of animals killed at the end of the study.

In addition, information of an old experiment exists; however, only a sheet of testing results is available, thus details on testing procedures and results are lacking and a reliability cannot be assigned. It is here mentioned only for completeness sake. The acute oral LD50 in rats was indicated as greater than 5000 mg/kg (sheet of test results, 1977).

ACUTE INHALATION TOXICITY

No acute toxicity studies by inhalation route are available on Acid Yellow 218. Nevertheless, because of the physical state of the substance, inhalation is expected to be a not relevant route of exposure. The vapour pressure of the substance is estimated to be negligible; the particle size distribution showed that the 90 % of particles have a diameter higher than 105 µm. Thus, most of the particles of Acid Yellow 218 are not-respirable. This consideration, together with the consideration that the substance is manufactured and handled with suitable risk management measures and with the suitable personal protective equipments, allows to consider the possible absorption of the substance by inhalation route as negligible.

DERMAL ACUTE TOXICITY

Information about an old experiment exists; however, only a sheet of testing results is available, thus details on testing procedures and results are lacking and a reliability cannot be assigned. It is here mentioned only for completeness sake. The acute dermal LD50 in rats was indicated as greater than 5000 mg/kg (sheet of test results, 1975).

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), substances can be allocated to one of four toxicity categories based on acute toxicity by oral, dermal or inhalation route according to 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 5000 mg/kg body weight, thus the test substance is out of any classification limit for acute oral toxicity (oral acute toxicity category 4: 300 < ATE ≤ 2000 mg/kg bw).

In conclusion, the test substance is non classified for oral acute toxicity, according to the CLP Regulation (EC 1272/2008).